ELIZA

return kwic search for significantly out of >500 occurrences
583352 occurrences (No.14 in the rank) during 5 years in the PubMed. [cache]

395) Finally, we showed that chlorpromazine, one of the candidate drugs, can significantly inhibit mouse follicle rupture in vivo.

--- ABSTRACT ---

PMID:34260376 DOI:10.1073/pnas.2026403118

2021 Proceedings of the National Academy of Sciences of the United States of America

* A platform utilizing Drosophila ovulation for nonhormonal contraceptive screening.

- A significant unmet need for new contraceptive options for both women and men remains due to side-effect profiles, medical concerns, and the inconvenience of many currently available contraceptive products. Unfortunately, the development of novel nonsteroidal female contraceptive medicine has been stalled in the last couple of decades due to the lack of effective screening platforms. Drosophila utilizes conserved signaling pathways for follicle rupture, a final step in ovulation that is essential for female reproduction. Therefore, we explored the potential to use Drosophila as a model to screen compounds that could inhibit follicle rupture and be nonsteroidal contraceptive candidates. Using our ex vivo follicle rupture assay, we screened 1,172 Food and Drug Administration (FDA)-approved drugs and identified six drugs that could inhibit Drosophila follicle rupture in a dose-dependent manner. In addition, we characterized the molecular actions of these drugs in the inhibition of adrenergic signaling and follicle rupture. Furthermore, we validated that three of the four drugs consistently inhibited mouse follicle rupture in vitro and that two of them did not affect progesterone production. Finally, we showed that chlorpromazine, one of the candidate drugs, can significantly inhibit mouse follicle rupture in vivo. Our work suggests that Drosophila ovulation is a valuable platform for identifying lead compounds for nonsteroidal contraceptive development and highlights the potential of these FDA-approved drugs as novel nonsteroidal contraceptive agents.

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[frequency of next (right) word to significantly]

(1)44 higher	(17)6 with	(33)4 in	(49)2 faster
(2)35 increased	(18)5 and	(34)4 suppressed	(50)2 increases
(3)33 associated	(19)5 better	(35)3 (p	(51)2 influence
(4)25 reduced	(20)5 enhanced	(36)3 change	(52)2 inhibit
(5)20 lower	(21)5 enriched	(37)3 diminished	(53)2 larger
(6)19 decreased	(22)5 less	(38)3 increase	(54)2 lowered
(7)15 different	(23)5 related	(39)3 longer	(55)2 modified
(8)14 more	(24)4 null	(40)2 (P	(56)2 over
(9)13 greater	(25)4 altered	(41)2 affected	(57)2 positively
(10)12 improved	(26)4 between	(42)2 alleviated	(58)2 prolong
(11)11 correlated	(27)4 by	(43)2 alter	(59)2 reduce
(12)10 inhibited	(28)4 downregulated	(44)2 at	(60)2 reduces
(13)6 attenuated	(29)4 elevated	(45)2 changed	(61)2 reversed
(14)6 predicted	(30)4 impact	(46)2 declined
(15)6 to	(31)4 improve	(47)2 decreased,
(16)6 upregulated	(32)4 improves	(48)2 expanded

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--- WordNet output for significantly --- =>きわめて, 意味深く, 意味ありげに Overview of adv significantly The adv significantly has 3 senses (first 2 from tagged texts) 1. (6) significantly -- (in a statistically significant way; "the two groups differed significantly") 2. (3) significantly -- (in a significant manner; "our budget will be significantly affected by these new cuts") 3. importantly, significantly -- (in an important way or to an important degree; "more importantly, Weber held that the manifold meaning attached to the event by the social scientist could alter his definition of the concrete event itself") --- WordNet end ---