The network Regulation of Yiqi Jiedu Formulae against Cerebral Ischemia Based on Central-periphery Inflammation System
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ABSTRACT:
ORGANISM(S): Rattus norvegicus Rattus
PROVIDER: GSE210512 | GEO | 2022/08/06
REPOSITORIES: GEO
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Project description:Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3. Importantly, pharmacological or genetic ablation of innervation preserved NK cell function and prevented post-stroke infection. Thus, brain ischemia compromises NK cell-mediated immune defenses through mechanisms that differ in the brain versus the periphery, and targeted inhibition of neurogenic innervation limits post-stroke infection.
2017-02-22 | GSE95100 | GEO
Project description:Prenatal alcohol exposure (PAE) is linked to elevated risk for systemic adult-onset diseases like hypertension, impaired glucose and immune regulation, and in animal models, to impaired recovery from acute onset diseases like cerebrovascular ischemic stroke. Recent evidence suggests that the gastrointestinal system rapidly becomes dysbiotic following cerebrovascular stroke, resulting in systemic inflammation. We hypothesized that a history of PAE would modify the systemic effects of stroke, and transduce exposure-dependent transcriptomic changes in downstream sentinel tissues of the enteric portal circulation that have previously been linked to biobehavioral outcomes in rodent PAE models. Pregnant Sprague Dawley rats were exposed to repeated episodes of vaporized ethanol or room air from gestational day 8 to 19. At 5 months, progeny from each treatment condition were subjected to unilateral endothelin-1 induced occlusion of the middle cerebral artery and outcomes evaluated after 2 days while other progeny stayed stroke-naïve. Stroke induced disabilities were assessed by behavioral assays (adhesive removal, Vibrissae evoked fore-limb placement, circling) and infarct size. The mesenteric adipose tissue and liver transcriptomes were assessed by sequencing, from age-matched stroke-exposed and stroke-naïve offspring. In stroke-naïve animals, pathway analysis identified rRNA processing as downregulated and citric acid cycle as upregulated in mesenteric adipose. Weighted gene correlation network analysis (WGCNA) identified, in the liver of stoke-naïve animals, a moderate but significant correlation between PAE status and necroptosis, a proinflammatory form of programmed cell death (Pearson’s r=0.554, p<0.05). Two days after a stroke, PAE rats exhibited worse neurological scores compared to controls (p<0.05). WGCNA after stroke identified an adipose gene network associated with B cell differentiation and NF-kappa B signaling as moderately correlated with post-stroke neurological function (Pearson's r=0.52, p=0.05). Post-stroke WGCNA also identified a liver proinflammatory gene network strongly correlated with post-stroke neurological function (Pearson's r=-0.63, p<0.01). PAE persistently alters the transcriptome of afferent tissue targets of enteric circulation in adult rat offspring. Moreover, PAE-linked enteric inflammation is correlated to worse outcomes following cerebrovascular ischemic stroke in adulthood. Enteric disturbances may mediate adverse brain health outcomes due to PAE in adulthood.
2023-08-29 | GSE217173 | GEO
Project description:Background and Purpose: Long noncoding RNAs (lncRNAs) are an emerging class of genomic regulatory molecules reported in neurodevelopment and many diseases. Despite extensive studies have identified lncRNAs and discovered their functions in CNS diseases, the function of lncRNAs in ischemia stroke remains poorly understood. Method: Ischemia was induced by transient middle cerebral artery occlusion. Expression profiles of lncRNAs, miRNAs and mRNAs after ischemia stroke were obtained using high throughput sequencing technology. A correlation network was constructed to predict lncRNA functions. LncRNA-miRNA-mRNA network was constructed to discover ceRNAs. Results: 1924 novel lncRNAs were identified, indicating that the ischemia stroke has a complex effect on lncRNAs. The top 10 regulated lncRNAs was validated by qRT-PCR. We have also predicted function of lncRNAs, and subjected them to gene co-expression network analysis, revealing the involvement of lncRNAs in many important biological process including injury and repair that are implicated in the regulation of ischemia stroke. Furthermore, lncRNAs mediated SMD (Staufen1-mediated mRNA decay) was analyzed and ceRNA (competitive endogenous RNAs) network was constructed in ischemia stroke. Conclusions: This study reports the genome-wide lncRNA profiles in ischemia stroke using high throughput sequencing and constructs a systematic lncRNA-miRNA-mRNA network which reveals a complex functional noncoding RNA regulatory network in ischemia stroke.
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2019-11-26 | GSE139378 | GEO
Project description:Stroke is a leading cause of adult disability and death. Inflammation plays an important role in stroke pathology, but the factors which promote brain inflammation in this setting remain to be fully defined. Here we investigate the meninges, the membranes that envelop the brain, for a potential role in modulating immune cell trafficking to the brain. We also investigate the potential of mast cells (MCs) to modulate this response as MCs are often considered as 'first responders' playing a critical role in the initiation and development of inflammation in many disease settings. We find that stroke increases expression of inflammatory and immune response genes in the meninges in mice consistent with a potential role in modulating immune cell trafficking. Moreover, genetic and cell transfer approaches identify MCs as important modulators of this response. Three categories of male mice were used: wild-type (WT) mice, mast cell-deficient (KO) mice, and mast cell-engrafted mice (EN), which are mast cell-deficient mice repaired of their mast cell deficiency by engraftment of mast cells i.v. 8-10 weeks prior to experimentation. The mouse strain was WBB6F1-Kit+/+ (wild-type ) and WBB6F1-KitW/W-v (mast cell-deficient ). Each mouse category was subdivided into two groups, naïve (N) and stroke (S), with n=3 per group. The stroke model was 30 minute filament occlusion of the middle cerebral artery. The dura were removed from the mouse brains at 2d post-stroke and from aged-matched naïve mice for microarray analysis. Dura were not pooled but run on separate arrays.
2014-07-31 | E-GEOD-51566 | biostudies-arrayexpress
Project description:Wang Bi Tablet (WBT) exhibits effective power in clinic during the treatment of rheumatoid arthritis (RA) in China. We aimed to employ the “integrative pharmacology strategy”, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to delineate the main active components and reveal the underlying mechanism of WBT acting on RA. UPLC-QTOF-MS/MS provided the chemical fingerprint of WBT and UNIFI 1.8 software assisted in chemical composition identification by matching the MSE raw data to the in-house library. The anti-inflammatory effect of WBT was evaluated in TNF-α- stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis was carried out based on Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP V2.0, http://www.tcmip.cn/). Functional enrichment and network visualization was performed by DAVID v6.8 and NaviGator v3.0 respectively. Altogether, 293 chemical constituents were preliminarily identified or tentatively characterized in the extract of WBT, and it could effectively against inflammatory response in TNF-α-stimulated RAW264.7 cells. One hundred and thirty-five hub genes were delineated based on the network construction of “Anti-inflammatory Core Genes-Putative Targets-RA genes”, which were mainly involved in inflammation-immune regulation, closely relating to the occurrence and development of RA, such as Cytokine-cytokine receptor interaction, Chemokine signaling pathway, etc., Forty-eight key active constituents were selected according to the frequency binding to hub targets and contents in WBT, corresponding to 13 herbal medicines. In summary, it is the first time to explore the active constituents and underlying mechanism of WBT acting on RA using integrative pharmacology strategy, which may provide an efficient way for the analysis of chemical constituents and exploration of pharmacological mechanism of TCM.
2021-05-10 | GSE165272 | GEO
Project description:Evaluation of the genome wide impact on gene expression of DNA-PK knockdown or enzymatic inhibition. DNA-PK expression is elevated in multiple tumor types. DNA-PK has recently been implicated in transcriptional regulation, so understanding genes modulated by DNA-PK may provide insight into disease progression 6 samples were analyzed. A genome-wide expression array was performed on a GeneChip Human Gene 2.0ST Array (Affymetrix, 902112) with C4-2 cells depleted of DNA-PK or treated with DNA-PK inhibitor for 24 hours
2015-07-13 | E-GEOD-63480 | biostudies-arrayexpress
Project description:To explore the biological connotation of eight syndromes of Rheumatoid Arthritis (RA) from the syndrome-symptom association network, and the relationship between the clinical characteristics of various syndromes and their key network target genes and pathways, which may offer clinicians auxiliary tools for diagnosis and treatment of RA patients with various traditional Chinese medicine (TCM) syndromes and promoting the developments of TCM Syndrome Theory. We used microarrays to detail the biological connotation of five syndromes (D-H, N) of Rheumatoid Arthritis (RA) and identified distinct classes of up-regulated and down-regulated genes during this process.
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