Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.

TGF-β promotes AP by inducing miR-216a targeting PTEN and Smad7, thus through PI3K/Akt and TGF-β feedback pathway.

Objectives We aimed to investigate the determinants of thrombus burden (TB) and the impact of thrombus aspiration (TA) on outcome in young adults with ST segment elevation myocardial infarction (STEMI). Background The determinants of TB in young STEMI patients are not fully understood now. Methods The 182 young (age ≤ 45 years) STEMI patients, who underwent coronary angiography and percutaneous coronary intervention (PCI) in our hospital from January 2013 to September 2016, were included. Angiographic TB and impact of TA on major adverse cardiac events (MACEs) were evaluated. Median clinical follow‐up period was 875 (641–1,052) days. Results All patients were male, mean age was 40 ± 5 years. High thrombus burden (HTB) was evidenced in 100 (54.9%) patients. TA was performed in 62 out 100 (62%) patients with high TB (HTB) during PCI. The prevalence of hypertension was significantly higher in the HTB group than in the low thrombus burden (LTB) group (75 vs. 17%, P < 0.001). The proportion of smoking, alcohol consumption, and family history of premature coronary artery disease were similar between HTB and LTB groups. During follow‐up, 2 patients died and 31 patients underwent repeat PCI. MACE rate was significantly higher in the HTB group than in the LTB group (24.0 vs. 9.8%, P = 0.012) and significantly lower in HTB patients with TA than HTB patients without TA (14.5 vs. 39.5%, P = 0.018). Conclusions Hypertension is an independent determinant of HTB and TA could be considered as an effective therapeutic option in young male STEMI patients with HTB.

We investigated the cardioprotective effect of renal ischemic postconditioning (RI-PostC) and its mechanisms in a rabbit model. Rabbits underwent 60 min of left anterior descending coronary artery occlusion (LADO) and 6 h of reperfusion. The ischemia-reperfusion (IR) group underwent LADO and reperfusion only. In the RI-PostC group, the left renal artery underwent 3 cycles of occlusion for 30 seconds and release for 30 seconds, before the coronary artery was reperfused. In the RI-PostC + GF109203X group, the rabbits received 0.05 mg/kg GF109203X (protein kinase C inhibitor) intravenously for 10 min followed by RI-PostC. Light microscopy and electron microscopy demonstrated that the RI-PostC group showed less pronounced changes, a smaller infarct region, and less apoptosis than the other two groups. Bcl-2 and Bax protein expression did not differ between the IR and RI-PostC + GF109203X groups. However, in the RI-PostC group, Bcl-2 protein expression was significantly higher and Bax protein expression was significantly lower than in the other two groups (P < 0.05). Changes in heart rate and mean arterial pressure were also smaller in the RI-PostC group than in the other two groups. These results indicate that RI-PostC can ameliorate myocardial ischemia-reperfusion injury and increase the Bcl-2/Bax ratio through a mechanism involving protein kinase C.