Magnetic double-network hydrogels for tissue hyperthermia and drug release.

Magnetic-field driven soft materials have found extensive applications in fields such as soft robotics, shape morphing and biomedicine. Compared to magnetoactive elastomers (MAEs), magnetic hydrogels have shown significant advantages for in vivo applications, because of their better biocompatibility, as well as their soft and wet nature. However, the poor mechanical properties and ion sensitivity of conventional magnetic hydrogels will severely limit their applications especially under physiological conditions. Double network hydrogels are tough and stable, but do not respond to environmental stimuli. Here magnetic double network (M-DN) hydrogels have been developed with outstanding mechanical performances and ion-resistant stability. M-DN hydrogels show a high modulus of ∼0.4 MPa and a high toughness of ∼1500 J m-2. The volume, magnetic and mechanical properties of M-DN hydrogels show negligible deterioration in ionic solutions. M-DN hydrogels exhibit magnetic responsiveness and have been used for tissue hyperthermia and drug release by magnetic induction heating. The induction heating behavior of M-DN hydrogels can be tuned to meet the clinical requirements, by changing the magnetic field strength or the composition of magnetic hydrogels. M-DN hydrogels may be inspiring to the development of responsive DN hydrogels and expand their more potential applications in load-bearing biomedical engineering.

11ß-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Development by Lentiviral Screening Based on Computational Modeling.

In this study, rat and human 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) have been cloned by lentiviral transduction and expressed by CHO-K1 cells. The results showed that recombinant plasmids contained R11bhsd1 or H11bhsd1 have been constructed, which is consistent with the gene bank respectively. A clone cell was selected with G418 and cultivated to express 11ß-HSD1. 11ß-HSD1 catalytic activity of rat and human were 99.5 and 98.7%, respectively, determined by scanning radiometer. And the cloned CHO-K1 cells expressed the protein of 11ß-HSD1 in a long-term and stable manner, which makes it suitable for screening 11ß-HSD1 inhibitor. The three-dimensional structure of 11ß-HSD1 was used for studying the interaction between inhibitor and enzyme by the binding poses predicted by AutoDock and LeDock software. The docking results revealed that compound 8 forms 2 hydrogen bonds with the residues of Gly-216 and Ile-218 in 11ß-HSD1, that is to say compound 8 maybe a good 11ß-HSD1 inhibitor. Moreover, C57BL/6 mice with R11bHsd1 overexpression had a higher body weight, glucose, total cholesterol, and triglyceride levels compared to the mice treated with an empty viral vector. The results might provide a beneficial foundation for selecting inhibitors of 11ß-HSD1 or for researching drug candidate mechanisms.

Curcumin as a potent and selective inhibitor of 11ß-hydroxysteroid dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats.

BACKGROUND: 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) activates glucocorticoid locally in liver and fat tissues to aggravate metabolic syndrome. 11ß-HSD1 selective inhibitor can be used to treat metabolic syndrome. Curcumin and its derivatives as selective inhibitors of 11ß-HSD1 have not been reported. METHODOLOGY: Curcumin and its 12 derivatives were tested for their potencies of inhibitory effects on human and rat 11ß-HSD1 with selectivity against 11ß-HSD2. 200 mg/kg curcumin was gavaged to adult male Sprague-Dawley rats with high-fat-diet-induced metabolic syndrome for 2 months. RESULTS AND CONCLUSIONS: Curcumin exhibited inhibitory potency against human and rat 11ß-HSD1 in intact cells with IC50 values of 2.29 and 5.79 µM, respectively, with selectivity against 11ß-HSD2 (IC50, 14.56 and 11.92 µM). Curcumin was a competitive inhibitor of human and rat 11ß-HSD1. Curcumin reduced serum glucose, cholesterol, triglyceride, low density lipoprotein levels in high-fat-diet-induced obese rats. Four curcumin derivatives had much higher potencies for Inhibition of 11ß-HSD1. One of them is (1E,4E)-1,5-bis(thiophen-2-yl) penta-1,4-dien-3-one (compound 6), which had IC50 values of 93 and 184 nM for human and rat 11ß-HSD1, respectively. Compound 6 did not inhibit human and rat kidney 11ß-HSD2 at 100 µM. In conclusion, curcumin is effective for the treatment of metabolic syndrome and four novel curcumin derivatives had high potencies for inhibition of human 11ß-HSD1 with selectivity against 11ß-HSD2.

Thymidylate synthase was associated with patient prognosis and the response to adjuvant therapy in bladder cancer.

OBJECTIVE: To investigate the expression of thymidylate synthase (TS), a key enzyme in DNA synthesis that is over-expressed in several cancer cells, in bladder cancer and its association with patient prognosis and the response to adjuvant therapy. PATIENTS AND METHODS: In all, 67 bladder tissue specimens were obtained from patients who had undergone transurethral resection (TUR). TS expression in bladder cancer and normal bladder tissue was analysed by immunohistochemistry. RESULTS: Of the 67 bladder tissue specimens, 47 (70%) and 10 (15%) had positive expression for TS in cancer and normal tissues, respectively. TS expression was greater in patients with Grade 3 (16/17, 94%) than in Grade 1 and 2 (31/50, 64%; P = 0.002). It was also greater in Stage T1 (14/14) than in Stage Ta (33/53, 62%; P = 0.001). Furthermore, patients with negative TS expression had a longer postoperative recurrence-free survival (RFS) than those with positive expression during the 5 year follow-up (P = 0.028). In the patients with positive TS-expressing tumours, adjuvant therapy significantly improved RFS (P < 0.001). CONCLUSIONS: High TS expression might be a marker of poor prognosis for patients with bladder cancer. In addition, patients with high TS expression might also be benefit from adjuvant therapy.