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

return kwic search for function out of >500 occurrences
288503 occurrences (No.86 in the rank) during 5 years in the PubMed. [cache]
179) Finally, we used cardiac magnetic resonance imaging to measure RV function and found that therapies using AAV1.hSERCA2a alone or combined with STAT3i significantly inhibited RV structural and functional changes in PNT/MCT-induced PAH.
--- ABSTRACT ---
PMID:34502015 DOI:10.3390/ijms22179105
2021 International journal of molecular sciences
* Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.
- Pulmonary arterial hypertension (PAH) is a devastating lung disease characterized by the progressive obstruction of the distal pulmonary arteries (PA). Structural and functional alteration of pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) contributes to PA wall remodeling and vascular resistance, which may lead to maladaptive right ventricular (RV) failure and, ultimately, death. Here, we found that decreased expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in the lung samples of PAH patients was associated with the down-regulation of bone morphogenetic protein receptor type 2 (BMPR2) and the activation of signal transducer and activator of transcription 3 (STAT3). Our results showed that the antiproliferative properties of SERCA2a are mediated through the STAT3/BMPR2 pathway. At the molecular level, transcriptome analysis of PASMCs co-overexpressing SERCA2a and BMPR2 identified STAT3 amongst the most highly regulated transcription factors. Using a specific siRNA and a potent pharmacological STAT3 inhibitor (STAT3i, HJC0152), we found that SERCA2a potentiated BMPR2 expression by repressing STAT3 activity in PASMCs and PAECs. In vivo, we used a validated and efficient model of severe PAH induced by unilateral left pneumonectomy combined with monocrotaline (PNT/MCT) to further evaluate the therapeutic potential of single and combination therapies using adeno-associated virus (AAV) technology and a STAT3i. We found that intratracheal delivery of AAV1 encoding SERCA2 or BMPR2 alone or STAT3i was sufficient to reduce the mean PA pressure and vascular remodeling while improving RV systolic pressures, RV ejection fraction, and cardiac remodeling. Interestingly, we found that combined therapy of AAV1.hSERCA2a with AAV1.hBMPR2 or STAT3i enhanced the beneficial effects of SERCA2a. Finally, we used cardiac magnetic resonance imaging to measure RV function and found that therapies using AAV1.hSERCA2a alone or combined with STAT3i significantly inhibited RV structural and functional changes in PNT/MCT-induced PAH. In conclusion, our study demonstrated that combination therapies using SERCA2a gene transfer with a STAT3 inhibitor could represent a new promising therapeutic alternative to inhibit PAH and to restore BMPR2 expression by limiting STAT3 activity.
--- ABSTRACT END ---
[
right
kwic]
[frequency of next (right) word to function]
(1)86 *null* (9)5 following (17)3 mutations (25)2 for
(2)72 of (10)5 was (18)3 not (26)2 have
(3)68 and (11)5 with (19)3 were (27)2 including
(4)63 in (12)4 by (20)3 which (28)2 measures
(5)16 is (13)4 has (21)2 after (29)2 or
(6)13 as (14)4 tests (22)2 among (30)2 quality
(7)5 are (15)4 to (23)2 data (31)2 that
(8)5 associated (16)3 at (24)2 during (32)2 variants

add keyword

--- WordNet output for function --- =>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式 Overview of noun function The noun function has 7 senses (first 3 from tagged texts) 1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a mathematical relation such that each element of a given set (the domain of the function) is associated with an element of another set (the range of the function)) 2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to bore holes"; "ballet is beautiful but what use is it?") 3. (7) function, office, part, role -- (the actions and activities assigned to or required or expected of a person or group; "the function of a teacher"; "the government must do its part"; "play its role") 4. function -- (a relation such that one thing is dependent on another; "height is a function of age"; "price is a function of supply and demand") 5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function") 6. affair, occasion, social occasion, function, social function -- (a vaguely specified social event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly endless round of social functions") 7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger computer program) Overview of verb function The verb function has 3 senses (first 3 from tagged texts) 1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work anymore") 2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table"; "The female students served as a control group"; "This table would serve very well"; "His freedom served him well"; "The table functions as a desk") 3. (1) officiate, function -- (perform duties attached to a particular office or place or function; "His wife officiated as his private secretary") --- WordNet end ---