ELIZA

return kwic search for used out of >500 occurrences
821596 occurrences (No.5 in the rank) during 5 years in the PubMed. [no cache] 500 found

303) Doxorubicin (DOX) is widely used as an anti-cancer agent although it causes irreversible cardiomyopathy by increasing oxidative stress and deregulating nitric oxide production.

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PMID:23628005 DOI:10.1016/j.otsr.2013.03.006

2015 Current vascular pharmacology

* The prostaglandin agonist beraprost aggravates doxorubicin-mediated apoptosis by increasing iNOS expression in cardiomyocytes.

- Doxorubicin (DOX) is widely used as an anti-cancer agent although it causes irreversible cardiomyopathy by increasing oxidative stress and deregulating nitric oxide production. Beraprost (BPS), a stable prostacyclin (PGI2) analog, is a potent vasodilator that has beneficial effects on myocardial ischemia. The objectives of the present study were to delineate the uncertain effects of prostcyclin therapy on DOX induced cardiomyopathy and to explore the mechanisms underlying PGI2 and DOX interaction. For this reason, we stimulated endogenous PGI2 production using bicistronic COX-1/PGIS gene transfer and BPS supplementation, and investigated the effects on DOX-induced cardiomyopathy. Caspase-dependent protein content, lactate dehydrogenase (LDH), DNA fragmentation, and TUNEL positive cells were elevated in DOX-treated cardiomyocytes. These indicators were further elevated by adenovirus-COX- 1/PGIS transfection or BPS supplementation. In addition, PGI2 overexpression further increased iNOS expression and superoxide accumulation in cardiomyocytes compared with DOX alone, which may be the reason for aggravated cytotoxicity. Moreover, BPS can induce cAMP response elements (CRE) binding to the iNOS promoter and phospho- cAMP response element binding protein (CREB) expression in a cyclic AMP-dependent manner. Our in vivo studies show that MnTBAP and aminoguanidine treatment of DOX and BPS co-administered in mice can attenuate caspase-3 and PARP-1 protein expression, and improve mouse survival, as observed in the iNOS gene-deleted mice. In conclusion, we demonstrated that BPS or adv-COX-1/PGIS increases PGI2 levels through iNOS expression and peroxynitrite production, via CREB protein phosphorylation; thereby aggravating DOX-mediated cardiotoxicity.

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(1)154 to	(6)9 a	(11)3 with	(16)2 only
(2)83 in	(7)8 the	(12)2 at	(17)2 successfully
(3)49 for	(8)6 and	(13)2 during
(4)48 as	(9)4 by	(14)2 insecticides
(5)31 null	(10)4 data	(15)2 on

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--- WordNet output for used --- =>1.〜に慣れて, 2.用いられた, 中古の Overview of verb use The verb use has 6 senses (first 3 from tagged texts) 1. (603) use, utilize, utilise, apply, employ -- (put into service; make work or employ for a particular purpose or for its inherent or natural purpose; "use your head!"; "we only use Spanish at home"; "I can't use this tool"; "Apply a magnetic field here"; "This thinking was applied to many projects"; "How do you utilize this tool?"; "I apply this rule to get good results"; "use the plastic bags to store the food"; "He doesn't know how to use a computer") 2. (12) use, habituate -- (take or consume (regularly or habitually); "She uses drugs rarely") 3. (8) use, expend -- (use up, consume fully; "The legislature expended its time on school questions") 4. use -- (seek or achieve an end by using to one's advantage; "She uses her influential friends to get jobs"; "The president's wife used her good connections") 5. practice, apply, use -- (avail oneself to; "apply a principle"; "practice a religion"; "use care when going down the stairs"; "use your common sense"; "practice non-violent resistance") 6. use -- (habitually do something (use only in the past tense); "She used to call her mother every week but now she calls only occasionally"; "I used to get sick when I ate in that dining hall"; "They used to vacation in the Bahamas") Overview of adj used The adj used has 3 senses (first 3 from tagged texts) 1. (4) used -- (employed in accomplishing something; "the principle of surprise is the most used and misused of all the principles of war"- H.H.Arnold & I.C.Eaker) 2. (1) exploited, ill-used, put-upon, used, victimized, victimised -- (of persons; taken advantage of; "after going out of his way to help his friend get the job he felt not appreciated but used") 3. (1) secondhand, used -- (previously used or owned by another; "bought a secondhand (or used) car") --- WordNet end ---