Synthesis and biological evaluation of novel curcuminoid derivatives.

Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a-h, 15a-h and 19a-d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 µM /mL against selected medically important Gram-positive cocci (S. aureus and S. viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 µM.

Microinjection of urotensin II into the rostral ventrolateral medulla increases sympathetic vasomotor tone via the GPR14/ERK pathway in rats.

The present study aimed to reveal the effects of urotensin II (UII) on sympathetic vasomotor tone in the rostral ventrolateral medulla (RVLM). UII (0.3, 3, and 30 nmol/L, 50 nL) was microinjected into the RVLM. Blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured to determine the sympathetic vasomotor tone. BP, HR, and RSNA were simultaneously recorded after drugs had been microinjected into the RVLM. Microinjection of UII (0.3, 3, and 30 nmol/L, 50 nL) into the RVLM significantly increased BP, HR, and RSNA. Pretreatment with BIM23127 (300 nmol/L, 50 nL), a potent antagonist of the UII receptor GPR14, abolished the effect of UII. Previous microinjection of PD98059 (25 µmol/L, 50 nL), an inhibitor of ERK, significantly suppressed the effects of UII. Preinjection of an inhibitor of the N-type Ca2+ channel, ω-conotoxin GVIA (50 nmol/L, 50 nL), inhibited the effects of UII. The present study demonstrated that microinjection of UII into the RVLM significantly increased sympathetic vasomotor tone, which was mediated by the GPR14/ERK/N-type Ca2+ channel pathway. UII may become a novel therapeutic target for autonomic nervous system regulation, especially in hypertension.

Microinjection of resveratrol into rostral ventrolateral medulla decreases sympathetic vasomotor tone through nitric oxide and intracellular Ca2+ in anesthetized male rats.

AIM: To define the effect of resveratrol (RES) on the central regulation of blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA). METHODS: RES was microinjected into the rostral ventrolateral medulla (RVLM), and BP, HR, and RSNA were recorded simultaneously in anesthetized rats. RESULTS: A microinjection of RES (20, 40, and 80 micromol/L, 0.2 microL) into the RVLM dose dependently decreased BP, HR, and RSNA. Pretreatment with an anti-estrogen tamoxifen (100 micromol/L, 0.2 microL) did not affect the effects of RES. Pretreatment with NG-nitro- L-arginine methyl ester (100 micromol/L, 0.2 microL), an inhibitor of nitric oxide (NO) synthase, could completely abolish the effect of RES. A prior microinjection of Bay K8644 (500 nmol/L, 0.2 microL), an agonist of calcium channels, could also abrogate the effect of RES. Prior administration of a potent inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L, 0.2 microL), could partially attenuate the inhibitory effect of RES. CONCLUSION: The results suggest that a microinjection of RES into the RVLM inhibits BP, HR, and RSNA. The effects may be mediated by NO synthesis and a decrease in Ca2+ influx, in which protein tyrosine kinase is involved.

Enhanced electrical conductivity in polystyrene nanocomposites at ultra-low graphene content.

We compared the electrical conductivity of multiwalled-carbon-nanotube/polystyrene and graphene/polystyrene composites. The conductivity of polystyrene increases from ∼6.7 × 10(-14) to ∼3.49 S/m, with an increase in graphene content from ∼0.11 to ∼1.1 vol %. This is ∼2-4 orders of magnitude higher than for multiwalled-carbon-nanotube/polystyrene composites. Furthermore, we show that the conductivity of the graphene/polystyrene system can be significantly enhanced by incorporation of polylactic acid. The volume-exclusion principle forces graphene into the polystyrene-rich regions (selective localization) and generates ∼4.5-fold decrease in its percolation threshold from ∼0.33 to ∼0.075 vol %.