ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for significantly out of >500 occurrences
583352 occurrences (No.14 in the rank) during 5 years in the PubMed. [cache]
257) Intraperitoneal injection of 2-APB (1 mg/kg per day) significantly attenuated the development of PH and partially reversed established PH in mice.
--- ABSTRACT ---
PMID:34704831 DOI:10.1152/ajplung.00159.2021
2021 American journal of physiology. Lung cellular and molecular physiology
* TRPC6, a therapeutic target for pulmonary hypertension.
- Idiopathic pulmonary arterial hypertension (PAH) is a fatal and progressive disease. Sustained vasoconstriction due to pulmonary arterial smooth muscle cell (PASMC) contraction and concentric arterial remodeling due partially to PASMC proliferation are the major causes for increased pulmonary vascular resistance and increased pulmonary arterial pressure in patients with precapillary pulmonary hypertension (PH) including PAH and PH due to respiratory diseases or hypoxemia. We and others observed upregulation of TRPC6 channels in PASMCs from patients with PAH. A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) in PASMC triggers PASMC contraction and vasoconstriction, while Ca2+-dependent activation of PI3K/AKT/mTOR pathway is a pivotal signaling cascade for cell proliferation and gene expression. Despite evidence supporting a pathological role of TRPC6, no selective and orally bioavailable TRPC6 antagonist has yet been developed and tested for treatment of PAH or PH. In this study, we sought to investigate whether block of receptor-operated Ca2+ channels using a nonselective blocker of cation channels, 2-aminoethyl diphenylborinate (2-APB, administered intraperitoneally) and a selective blocker of TRPC6, BI-749327 (administered orally) can reverse established PH in mice. The results from the study show that intrapulmonary application of 2-APB (40 µM) or BI-749327 (3-10 µM) significantly and reversibly inhibited acute alveolar hypoxia-induced pulmonary vasoconstriction. Intraperitoneal injection of 2-APB (1 mg/kg per day) significantly attenuated the development of PH and partially reversed established PH in mice. Oral gavage of BI-749327 (30 mg/kg, every day, for 2 wk) reversed established PH by ∼50% via regression of pulmonary vascular remodeling. Furthermore, 2-APB and BI-749327 both significantly inhibited PDGF- and serum-mediated phosphorylation of AKT and mTOR in PASMC. In summary, the receptor-operated and mechanosensitive TRPC6 channel is a good target for developing novel treatment for PAH/PH. BI-749327, a selective TRPC6 blocker, is potentially a novel and effective drug for treating PAH and PH due to respiratory diseases or hypoxemia.
--- ABSTRACT END ---
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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 ---