Metabolomic and Network Analysis of Pharmacotherapies for Sensorineural Hearing Loss

@article{Muurling2014MetabolomicAN,
  title={Metabolomic and Network Analysis of Pharmacotherapies for Sensorineural Hearing Loss},
  author={Tjeerd J Muurling and Konstantina M. Stankovic},
  journal={Otology \& Neurotology},
  year={2014},
  volume={35},
  pages={1–6}
}
Hypothesis Different pharmacotherapies for sensorineural hearing loss (SNHL) are interconnected in metabolic networks with molecular hubs. Background Sensorineural hearing loss is the most common sensory deficit worldwide. Dozens of drugs have shown efficacy against SNHL in animal studies and a few in human studies. Analyzing metabolic networks that interconnect these drugs will point to and prioritize development of new pharmacotherapies for human SNHL. Methods Drugs that have shown efficacy… 
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References

SHOWING 1-10 OF 32 REFERENCES
A Comprehensive Network and Pathway Analysis of Human Deafness Genes
  • G. Stamatiou, K. Stankovic
  • Medicine, Biology
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
  • 2013
TLDR
A number of molecules that are likely to be key mediators of genetic hearing loss were identified through three different network and pathway analyses and included new candidate genes for deafness.
Drug Off-Target Effects Predicted Using Structural Analysis in the Context of a Metabolic Network Model
TLDR
This study represents a novel integration of structural and systems biology and a first step towards computational systems medicine and has important implications for drug development and personalized medicine.
Gaining Insight into Off-Target Mediated Effects of Drug Candidates with a Comprehensive Systems Chemical Biology Analysis
TLDR
This work presents a workflow that leverages data from chemogenomics based target predictions with Systems Biology databases to better understand off-target related toxicities and links between pathways and particular adverse effects are established.
Unveiling the role of network and systems biology in drug discovery.
Network medicine: a network-based approach to human disease
TLDR
Advances in this direction are essential for identifying new disease genes, for uncovering the biological significance of disease-associated mutations identified by genome-wide association studies and full-genome sequencing, and for identifying drug targets and biomarkers for complex diseases.
Network medicine
Microarray analysis of the effect of dexamethasone on murine cochlear explants
TLDR
The microarray analysis identified 39 genes whose expression is markedly up- or down-regulated by dexamethasone in the cochlear tissue and several are suggested to have protective effects in the traumatized inner ear.
Systems biology approaches and tools for analysis of interactomes and multi-target drugs.
TLDR
Targeting cellular function as a system rather than on the level of the single target, significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity.
Whole Genome Gene Expression Analysis Reveals Casiopeína-Induced Apoptosis Pathways
TLDR
This work presents a model proposal centered in the role played by intrinsic apoptosis triggered by oxidative stress caused by the chemotherapeutic agent Casiopeínas, inferred based on genome wide expression profiling in cervix cancer cells, as well as statistical and computational tests.
Gene expression and miR profiles of human corneal fibroblasts in response to dexamethasone.
TLDR
Evaluated genome microarray and microRNA analyses support a complex role for DEX-induced changes in resident cells that may have implications in the clinical management of corneal inflammation with topical glucocorticoids and DEX may exert posttranscriptional gene regulation through miRs.
...
...