Recently, large amount of real-world data (RWD), such as insurance claims data and self-reports of adverse drug reactions become available. Statistical analysis of RWD has made it possible to identify novel and unexpected confounding factors that influence the occurrence of adverse events or spontaneous disease in humans. Such drug-drug interactions lead to the elucidation of adverse event mechanisms and the discovery of new drug targets. In addition, hypotheses derived from RWD may have high clinical predictive value. In this review, the author shows how RWD analysis can lead to the discovery of drug targets, by introducing examples of research reports.
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Icariin(ICA)
affects the EMT and cancer stem cell-like character of breast cancer cells. The
main mechanism is to influence the characteristics of EMT and cancer stem
cell-like character of breast cancer cells by regulating the TGFβ/SMAD2
signaling pathway, which in turn affects the migration of breast cancer cells. In addition, we have found not only ICA inhibits proliferation, EMT and
stem cell-like character of breast cancer cells by silencing lncRNA NEAT1, but NEAT1
can exert anti-breast cancer effects through TGFβ/SMAD2 signaling pathway. Overall, we
hypothesized that ICA could inhibit the proliferation, EMT and cancer stem
cell-like character of breast cancer cells through the NEAT1/TGFβ/SMAD2 axis
and suppress breast cancer migration.
This study examined whether the approved sequence of vedolizumab and ustekinumab impacts the results of studies conducted in the EU, comparing the effectiveness of these drugs in Crohn's disease (CD) patients who failed anti-TNFα treatment. The authors conducted this study in Japan, where the approved sequence of drugs is different from that of the EU. They analyzed data from 256 CD patients from the Japanese claims database. The results suggested that ustekinumab is a more effective treatment option than vedolizumab for CD patients who failed anti-TNFα treatment, and this finding remains consistent across both Japan and the EU.
The authors investigated concurrent effects of hypoxia on physiological signals by simultaneously recording local field potentials in the primary motor, primary somatosensory and anterior cingulate cortices as well as electrocardiograms, electroolfactograms, and electromyograms of rats in acutely hypoxic environment. When they were exposed to acute hypoxia, alpha oscillations in the primary motor cortex were impaired. Moreover, the authors demonstrated that heart rate and respiratory rate were increased during acute hypoxia and high heart rate was maintained even after the oxygen level returned to the baseline. Altogether, this study characterizes a systemic effect of atmospheric hypoxia from physiological viewpoints.
(-)-Epigallocatechin-3-gallate (EGCg) is known to upregulate neprilysin, an Aβ-degrading enzyme. To clarify the mechanism underlying this process, the authors screened catechin-binding proteins by pull-down assay with magnetic beads and LC-tandem mass spectrometry and identified synaptic vesicle membrane protein VAT-1 homolog (VAT1). Surface plasmon resonance analysis revealed a direct binding of recombinant VAT1 protein to EGCg or its alkylated derivative NUP-15 with comparable affinity to the other EGCg binding proteins reported previously. Furthermore, the authors found that VAT1 prevented the upregulation of neprilysin by EGCg or NUP-15 through binding to and inactivating them in the cells overexpressing VAT1.