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Aims: Our aim was to test the hypothesis that angiotensin II receptor blockade combined with exercise training after myocardial infarction (MI) could attenuate post-MI left ventricular remodelling and preserve cardiac function. [ABSTRACT FROM PUBLISHER]

Thyroid hormone (T3) induces alteration of myosin heavy chain (MHC) α and β in myocardium. A significant decrease in serum T3 is observed in patients following MI. We investigated the effect of post-MI exercise training on gene expressions of thyroid hormone receptor (TR) α and β and MHC α and β in rats with MI. Seven-week-old rats were surgically induced MI (∼40% infarct of left ventricle). Rats were assigned into three groups (n=4/group) including a sham-operated control group (Sham), a sedentary group with MI (Sed-MI) and an exercise group with MI (Ex-MI). Ex-MI rats exercised at 16m/min, 50min/d, and 5d/wk for 8 wks starting one week post-MI. Real-time PCR was performed to analyze gene expressions on myocardium of the non-infarct left ventricles. The results showed that both TR-α and -β mRNA in Sed-MI group (2.0±0.11 and 1.58±0.11 folds compared to Sham) were significantly (p<0.05) high than that in Ex-MI (1.12±0.35 and 0.69±0.18). There was no significant difference (p>0.05) in MHC-β mRNA between Sed-MI (0.43±0.06) and Ex-MI (0.344±0.10) groups. MHC-β mRNA in Sed-MI (4.76±0.11) was significantly (p<0.05) higher than Ex-MI (2.68±0.28). These results suggest that post-MI training may attenuate TR and MHC-β gene expressions in the non-infarct LV. Supported by NIH grant (HL074273). [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells generate proinflammatory cytokines that are required to contain infections and tumor growth. However, the posttranscriptional mechanisms that regulate NK cell functions are not fully understood. Here, we define the role of the microRNA cluster known as Mirc11 (which includes miRNA-23a, miRNA-24a , and miRNA-27a ) in NK cell-mediated proinflammatory responses. Absence of Mirc11 did not alter the development or the antitumor cytotoxicity of NK cells. However, loss of Mirc11 reduced generation of proinflammatory factors in vitro and interferon-γ-dependent clearance of Listeria monocytogenes or B16F10 melanoma in vivo by NK cells. These functional changes resulted from Mirc11 silencing ubiquitin modifiers A20, Cbl-b, and Itch, allowing TRAF6-dependent activation of NF-κB and AP-1. Lack of Mirc11 caused increased translation of A20, Cbl-b, and Itch proteins, resulting in deubiquitylation of scaffolding K63 and addition of degradative K48 moieties on TRAF6. Collectively, our results describe a function of Mirc11 that regulates generation of proinflammatory cytokines from effector lymphocytes., (©2019 American Association for Cancer Research.)