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

Recent increase of international travelers raises awareness of travel-related infections. Travelers' diarrhea is the most common and caused by diarrheagenic E. coli and other patho- gens. Undifferentiated fever challenges physicians to correctly diagnose and includes ma- laria, dengue, and enteric fever. The pre-test probability for a disease which causes undiffer- entiated fever largely depends on the travel destination. Malaria is most common in travelers returning from sub-Saharan Africa while dengue is most common those returning from Southeast Asia and Latin America. Screening for asymptomatic travelers is not generally rec- ommended, but for long-term travelers and immigrants. Following outbreaks of highly infectious diseases in the past decades, hospital prepared- ness for travel-related infections focuses on infection prevention and control. Emerging viral pneumonias such as Middle East respiratory syndrome (MERS) and avian influenza H7N9 are major concerns. As seen in the largest outbreak of Ebola virus disease in West Africa, imported viral hemorrhagic fever such as Lassa fever is another concern. Since multidrug resistant bacteria silently spread globally by infected travelers, it would be of help to install appropriate isolation precaution for travelers with history of hospital admission abroad.
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PMID:Case management of ill travelers with infectious diseases. 3055 Jun 66