Treatment-related NEPC is an often under-recognized late manifestation of PCa with poor prognosis. Our study found that Gleason score was the only independent factor contributing to TTNEPC. Once NEPC is diagnosed, type of treatment and the number of organs with metastatic disease were the most important factors related to survival.

No abstract

This study tests whether or not post-exercise oxygen consumption rates (M ·  2 ) in fish are dependent upon how exhaustion is induced. A group of eight Atlantic cod (Gadus morhua) were each exercised using (1) a critical swimming speed (U crit ) protocol, (2) an exercise protocol designed to measure anaerobic capacity of fish (U burst ), and (3) a protocol in which the fish were chased to exhaustion manually. M ·  2 was measured for a 2-h period following exhaustion induced by all three exercise regimes (U crit , U burst and chase). Post-exercise M ·  2 following exhaustion from the U burst and chase protocols were significantly higher than post-exercise M ·  2 following the U crit protocol. Each fish during the U crit protocol exhibited maximal M ·  2 during exercise rather than during recovery, yet 75% of the fish during U burst recovery and 100% during chase recovery exhibited M ·  2 higher than that measured during U crit exercise. These results, as well as the large interindividual variations in M ·  2 among the eight fish, show that postexhaustion M ·  2 is specific to the exercise regime employed, thus, investigators must exercise caution when combining results from different exercise protocols and/or individuals.1995 The Fisheries Society of the British Isles

Clinical therapy of doxorubicin (DOX) is limited due to its cardiotoxicity. miR-146a was proved as a protective factor in many cardiovascular diseases, but its role in chronic DOX-induced cardiotoxicity is unclear. The objective of this study was to demonstrate the role of miR-146a in low-dose long-term DOX-induced cardiotoxicity. Experiments have shown that DOX intervention caused a dose-dependent and time-dependent cardiotoxicity involving the increased of apoptosis and dysregulation of autophagy. The cardiotoxicity was inhibited by overexpressed miR-146a and was more severe when miR-146a was downgraded. Further research proved that miR-146a targeted TATA-binding protein (TBP) associated factor 9b (TAF9b), a coactivator and stabilizer of P53, indirectly destroyed the stability of P53, thereby inhibiting apoptosis and improving autophagy in cardiomyocytes. Besides, miR-146a knockout mice were used for in vivo validation. In the DOX-induced model, miR-146a deficiency made it worse whether in cardiac function, cardiomyocyte apoptosis or basal level of autophagy, than wild-type. In conclusion, miR-146a partially reversed the DOX-induced cardiotoxicity by targeting TAF9b/P53 pathway to attenuate apoptosis and adjust autophagy levels.

Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression.