Tanshinone IIA Attenuates the Inflammatory Response and Apoptosis after Traumatic Injury of the Spinal Cord in Adult Rats

BACKGROUND: Spinal cord injury (SCI), including immediate mechanical injury and secondary injury, is associated with the inflammatory response, apoptosis and oxidative stress in response to traumatic injury. Tanshinone IIA (TIIA) is one of the major extracts obtained from Salvia miltiorrhiza BUNGE, which has anti-inflammatory and anti-apoptotic effects on many diseases. However, little is known about the effects of TIIA treatment on SCI. Therefore, the aim of the present study is to evaluate the pharmacological action of TIIA on secondary damage and the underlying mechanisms of experimental SCI in rats. METHODOLOGY/PRINCIPAL FINDINGS: SCI was generated using a weight drop device on the dorsal spinal cord via a two-level T9-T11 laminectomy. SCI in rats resulted in severe trauma, characterized by locomotor disturbance, edema, neutrophil infiltration, the production of astrocytes and inflammatory mediators, apoptosis and oxidative stress. TIIA treatment (20 mg/kg, i.p.) after SCI induced significant effects: (1) improved motor function (Basso, Beattie and Bresnahan scores), (2) reduced the degree of tissue injury (histological score), neutrophil infiltration (myeloperoxidase activity) and the expression of astrocytes, (3) inhibited the activation of SCI-related pathways, such as NF-κB and MAPK signaling pathways, (4) decreased the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and iNOS, (5) reduced apoptosis (TUNEL staining, and Bcl-2 and caspase-3 expression) and (6) reversed the redox state imbalance. CONCLUSIONS/SIGNIFICANCE: The results clearly show that TIIA has a prominent protective effect against SCI through inhibiting the inflammatory response and apoptosis in the spinal cord tissue after SCI

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Deregulation of microRNA expression in purified T and B lymphocytes from patients with primary Sjogren's syndrome

International audienceAbstract Objective MicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren’s syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach. Methods Two independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs. A selection of differentially expressed miRNAs was replicated in the second cohort using specific qPCR assays. Results A major difference in miRNA expression patterns was observed between the lymphocyte populations from patients with pSS and controls. In CD4 T lymphocytes, hsa-let-7d-3p, hsa-miR-155–5 p, hsa-miR-222–3 p, hsa-miR-30c-5p, hsa-miR-146a-5p, hsa-miR-378a-3p and hsa-miR-28–5 p were significantly differentially expressed in both the discovery and the replication cohort. In B lymphocytes, hsa-miR-378a-3p, hsa-miR-222–3 p, hsa-miR-26a-5p, hsa-miR-30b-5p and hsa-miR-19b-3p were significantly differentially expressed. Potential target mRNAs were enriched in disease relevant pathways. Expression of B-cell activating factor (BAFF) mRNA was inversely correlated with the expression of hsa-miR-30b-5p in B lymphocytes from patients with pSS and functional experiments showed increased expression of BAFF after inhibiting hsa-miR-30b-5p. Conclusions This study demonstrates major miRNAs deregulation in T and B cells from patients with pSS in two independent cohorts, which might target genes known to be involved in the pathogenesis of pSS

aCNViewer: Comprehensive genome-wide visualization of absolute copy number and copy neutral variations

<div><p>Motivation</p><p>Copy number variations (CNV) include net gains or losses of part or whole chromosomal regions. They differ from copy neutral loss of heterozygosity (cn-LOH) events which do not induce any net change in the copy number and are often associated with uniparental disomy. These phenomena have long been reported to be associated with diseases and particularly in cancer. Losses/gains of genomic regions are often correlated with lower/higher gene expression. On the other hand, loss of heterozygosity (LOH) and cn-LOH are common events in cancer and may be associated with the loss of a functional tumor suppressor gene. Therefore, identifying recurrent CNV and cn-LOH events can be important as they may highlight common biological components and give insights into the development or mechanisms of a disease. However, no currently available tools allow a comprehensive whole-genome visualization of recurrent CNVs and cn-LOH in groups of samples providing absolute quantification of the aberrations leading to the loss of potentially important information.</p><p>Results</p><p>To overcome these limitations, we developed aCNViewer (Absolute CNV Viewer), a visualization tool for absolute CNVs and cn-LOH across a group of samples. aCNViewer proposes three graphical representations: dendrograms, bi-dimensional heatmaps showing chromosomal regions sharing similar abnormality patterns, and quantitative stacked histograms facilitating the identification of recurrent absolute CNVs and cn-LOH. We illustrated aCNViewer using publically available hepatocellular carcinomas (HCCs) Affymetrix SNP Array data (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189334#pone.0189334.g001" target="_blank">Fig 1A</a>). Regions 1q and 8q present a similar percentage of total gains but significantly different copy number gain categories (p-value of 0.0103 with a Fisher exact test), validated by another cohort of HCCs (p-value of 5.6e-7) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189334#pone.0189334.g002" target="_blank">Fig 2B</a>).</p><p>Availability and implementation</p><p>aCNViewer is implemented in python and R and is available with a GNU GPLv3 license on GitHub <a href="https://github.com/FJD-CEPH/aCNViewer" target="_blank">https://github.com/FJD-CEPH/aCNViewer</a> and Docker <a href="https://hub.docker.com/r/fjdceph/acnviewer/" target="_blank">https://hub.docker.com/r/fjdceph/acnviewer/</a>.</p><p>Contact</p><p><a href="mailto:[email protected]" target="_blank">[email protected]</a></p></div

Overlap between differentially methylated DNA regions in blood B lymphocytes and genetic at-risk loci in primary Sjögren's syndrome

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aCNViewer main options.

<p>aCNViewer main options.</p

Overview of the different steps handled by aCNViewer.

<p>aCNviewer can process Affymetrix and Illumina SNP arrays as well as NGS data. LRR and BAF files are obtained after processing SNP raw data by PennCNV for Affymetrix and a threshold quantile normalization (tQN) for Illumina and subsequent use of ASCAT for CNV and cn-LOH detection. For NGS data, paired tumoral and non-tumoral whole exome/genome sequencing bam data are converted into seqz format and processed by Sequenza for CNV detection. aCNViewer converts CNV data into a CNV matrix with the window size defined by the user and which is subsequently used to compute dendrograms and heatmaps. Quantitative stacked histograms can be generated using the same matrix or a matrix of segments at base resolution (default behaviour). Text files are also available through GISTIC [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189334#pone.0189334.ref033" target="_blank">33</a>] providing a robust statistical way to select recurrent CNVs.</p

Quantitative stacked histograms using 96 HCC samples on Affymetrix 500K Human Mapping Array data from [1].

<p>A) Frequency of CNV and cn-LOH events along the genome. The left axis indicates the frequency of gains or losses among the 96 samples and the legend below indicates the number of copy number gains or losses from the reference baseline. The black line indicates the frequency of cn-LOH along the genome in negative ordinates. B) Frequency of homozygous/heterozygous CNVs along the genome. Copy-neutral events / gains and losses are respectively displayed in positive and negative ordinates.</p