Dataset Information

Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury.

ABSTRACT: Spinal cord injury (SCI) leads to reactive inflammation and other harmful events that limit spinal cord regeneration. We propose an approach for studying the mechanisms at the levels of network topology, gene ontology, signaling pathways, and disease inference. We treated inflammatory mediators as toxic chemicals and retrieved the genes and interacting proteins associated with them via a set of biological medical databases and software. We identified >10,000 genes associated with SCI. Tumor necrosis factor (TNF) had the highest scores, and the top 30 were adopted as core data. In the core interacting protein network, TNF and other top 10 nodes were the major hubs. The core members were involved in cellular responses and metabolic processes, as components of the extracellular space and regions, in protein-binding and receptor-binding functions, as well as in the TNF signaling pathway. In addition, both seizures and SCI were highly associated with TNF levels; therefore, for achieving a better curative effect on SCI, TNF and other major hubs should be targeted together according to the theory of network intervention, rather than a single target such as TNF alone. Furthermore, certain drugs used to treat epilepsy could be used to treat SCI as adjuvants.

SUBMITTER: Zhu W

PROVIDER: S-EPMC6354014 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury.

Zhu Weiping W Chen Xuning X Ning Le L Jin Kan K

Scientific reports 20190130 1

Spinal cord injury (SCI) leads to reactive inflammation and other harmful events that limit spinal cord regeneration. We propose an approach for studying the mechanisms at the levels of network topology, gene ontology, signaling pathways, and disease inference. We treated inflammatory mediators as toxic chemicals and retrieved the genes and interacting proteins associated with them via a set of biological medical databases and software. We identified >10,000 genes associated with SCI. Tumor necr ...[more]

PMID: 30700814

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Project description:The purpose of the present study was to examine the efficacy of targeting inflammation as a means of improving mood following spinal cord injury (SCI) and explore the potential mechanisms of action.The study was a randomized, parallel-group, controlled, clinical trial (NCT02099890) whereby 20 participants with varying levels and severities of SCI were randomized (3:2) to either the treatment group, consisting of a 12-week anti-inflammatory diet, or control group. Outcome measures were assessed at baseline, 1 and 3 months, and consisted of CES-D scores of depression, markers of inflammation as assessed by various pro- and anti-inflammatory cytokines and several amino acids related to depression.A significant group × time interaction was found for CES-D (Center for Epidemiologic studies Depression Scale) score (p?=?0.01), the TRP/LNAA (tryptophan/large neutral amino acid) ratio (p?=?0.04), the composite score of pro-inflammatory cytokines (p?=?0.04), IL-1? (interleukin-1 beta) (p?=?0.04), and IFN-? (interferon gamma) (p?=?0.03). Pearson's r correlation showed significance between the ?IL-1? and both the ?CES-D score (r?=?0.740, p?<?0.01) and the ?KYN/TRP (kynurenine/tryptophan) ratio (r?=?0.536, p?=?0.02). The ?KYN/TRP ratio was also significantly correlated with the ?CES-D score (r?=?0.586, p?=?0.01). Mediation analysis showed that the relationship between the ?KYN/TRP ratio and the ?CES-D score was mediated by the ?IL-1?. Subgroup analysis showed that participants with high CES-D scores had significantly higher concentrations of IL-1?, and all correlations were maintained or strengthened within this subgroup.Overall, the results demonstrated the effectiveness of targeting inflammation as a means of improving mood in SCI, with potential mechanisms relating to the reduction in IL-1? and improvements in levels of neuroactive compounds related to the kynurenine pathway. Due to the limited sample size, results should be interpreted with caution; however, they are worthy of further examination due to the potential impact of inflammation on depression.ClinicalTrials.gov ID: NCT02099890 .

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Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury.

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Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury.

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