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return kwic search for demonstrated out of >500 occurrences
286534 occurrences (No.87 in the rank) during 5 years in the PubMed. [no cache] 500 found

8) 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.

--- ABSTRACT ---

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)158 that	(10)5 good	(19)3 excellent	(28)2 efficacy
(2)48 the	(11)5 increased	(20)3 more	(29)2 greater
(3)40 a	(12)5 significantly	(21)3 no	(30)2 how
(4)23 by	(13)4 as	(22)3 that,	(31)2 successful
(5)21 to	(14)4 better	(23)2 acceptable	(32)2 through
(6)13 in	(15)4 improved	(24)2 and	(33)2 using
(7)12 null	(16)4 its	(25)2 both
(8)11 an	(17)4 similar	(26)2 decreased
(9)8 for	(18)3 between	(27)2 differential

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--- WordNet output for demonstrated --- Overview of verb demonstrate The verb demonstrate has 4 senses (first 4 from tagged texts) 1. (24) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (22) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (2) attest, certify, manifest, demonstrate, evidence -- (provide evidence for; stand as proof of; show by one's behavior, attitude, or external attributes; "His high fever attested to his illness"; "The buildings in Rome manifest a high level of architectural sophistication"; "This decision demonstrates his sense of fairness") 4. (1) demonstrate, march -- (march in protest; take part in a demonstration; "Thousands demonstrated against globalization during the meeting of the most powerful economic nations in Seattle") Overview of adj demonstrated The adj demonstrated has 1 sense (first 1 from tagged texts) 1. (1) demonstrated -- (having been demonstrated or verified beyond doubt) --- WordNet end ---