Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI2, acting via cAMP/PKA, was found to increase contraction-associated protein expression in myometrial cells and to promote oxytocin-driven myometrial contractility. Cyclo-oxygenase-2 (COX-2) is the rate-limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX-2 expression, synthesis and activity. Three cAMP agonists (8-bromo-cAMP, forskolin and rolipram) increased COX-2 mRNA expression and further studies confirmed that this was associated with COX-2 protein synthesis and activity (increased PGE2 and PGI2 in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP-effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP-effector PDZ-GEF1-2, without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX-2 expression and that PGE2 acts through EP-2 to activate MAPK and increase COX-2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function.
Seven kinds of indigenous fruits and five imported fruits were compared for their "health quality." Methods including the calorific, antioxidant, and ion ratios were carried out. Results indicated the order of content (in mg/100g) was: Ca(2+) , Murcott orange (218.2) > Kiwifruit (200.0) > pineapple (138.5) > Golden kiwi (117.6); Mg(2+) , Pitaya (192.2), banana (88.0), Kiwifruit (63.4), and Golden kiwi (58.4); Zn(2+) , Pitaya (19.53) > pear (10.8) > Kiwifruit (6.09) > Irwin mango (4.58). Cu(2+) , Kiwifruit (0.70) > Red globe grape (0.67) > Golden kiwi (0.65) > Irwin mango (0.42) ≈ Pitaya (0.40). In terms of ion ratio, Pitaya showed Zn(2+) /Cu(2+) (48.8), Mg(2+) /Ca(2+) (6.7) and uniquely possessed selenium 0.002 mg/100 g; for pear, Zn(2+) /Cu(2+) = 37.2, while Kyoho grape, Red globe grape, and Golden kiwi revealed extremely high Fe(2+) /(Co(2+) +Ni(2+) ) ratios. On the other hands, Irwin mango and Pitaya astonishingly contained huge amount of inositol, reaching 3523.2 mg/100 g and 1998.7 mg/100 g, respectively. To evaluate the "health quality" of fruits, an overall ranking method by combining (a) the Function-directed Caloric Antioxidant Density (CAD) and (b) the ion ratio was developed. The finalized ranking of these selected fruits was: Pitaya > cherry > Irwin mango > Murcott orange = pineapple > banana > Golden kiwi > pear > Kiwifruit > Red globe grape > apple > Kyoho grape. Conclusively, this evaluation method is novel, contemporary and scientific, which could more clearly assess the "health quality" of fruits in view of nutritional, calorific, and antioxidant balance.
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