Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chaperone GRP78/Dna K is conserved throughout evolution down to prokaryotes. The GRP78 inhibitor OSU-03012 (AR-12) interacted with sildenafil (Viagra) or tadalafil (Cialis) to rapidly reduce GRP78 levels in eukaryotes and as a single agent reduce Dna K levels in prokaryotes. Similar data with the drug combination were obtained for: HSP70, HSP90, GRP94, GRP58, HSP27, HSP40 and HSP60. OSU-03012/sildenafil treatment killed brain cancer stem cells and decreased the expression of: NPC1 and TIM1; LAMP1; and NTCP1, receptors for Ebola/Marburg/Hepatitis A, Lassa fever, and Hepatitis B viruses, respectively. Pre-treatment with OSU-03012/sildenafil reduced expression of the coxsakie and adenovirus receptor in parallel with it also reducing the ability of a serotype 5 adenovirus or coxsakie virus B4 to infect and to reproduce. Similar data were obtained using Chikungunya, Mumps, Measles, Rubella, RSV, CMV, and Influenza viruses. OSU-03012 as a single agent at clinically relevant concentrations killed laboratory generated antibiotic resistant E. coli and clinical isolate multi-drug resistant N. gonorrhoeae and MRSE which was in bacteria associated with reduced Dna K and Rec A expression. The PDE5 inhibitors sildenafil or tadalafil enhanced OSU-03012 killing in N. gonorrhoeae and MRSE and low marginally toxic doses of OSU-03012 could restore bacterial sensitivity in N. gonorrhoeae to multiple antibiotics. Thus, Dna K and bacterial phosphodiesterases are novel antibiotic targets, and inhibition of GRP78 is of therapeutic utility for cancer and also for bacterial and viral infections.
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PMID:GRP78/BiP/HSPA5/Dna K is a universal therapeutic target for human disease. 2554 29

Research by The Psychological Record, 64(3), 433-440. doi:10.1007/s40732-014-0052-9, (2014) demonstrated the novel finding that the magnitude effect for medical outcomes does not reverse across delay and probability discounting as it does for monetary outcomes. We suggest that a possible reason for the lack of a reverse magnitude effect in nonmonetary outcomes is incomparable divisibility of discounted alternatives. To test whether the lack of a reverse magnitude effect in probability discounting of medical outcomes is due to incomparable divisibility of treatment effects, 4 studies were conducted. In the replication study, the effect observed by The Psychological Record, 64(3), 433-440. doi:10.1007/s40732-014-0052-9, (2014) was marginally not significant, although it was directionally consistent with their prediction of steeper discounting of small medical outcomes (as compared to large, defined as brain cancer) both in time and probability discounting. Our manipulation by substituting a divisible outcome (body paralysis) for an indivisible one (brain cancer) did not, however, bring expected results. We discuss the explanations and possible implications of introduced division for divisible and nondivisible medical outcomes.
Psychol Rec
PMID:You Cannot be Partially Pregnant: A Comparison of Divisible and Nondivisible Outcomes in Delay and Probability Discounting Studies. 2686 35