A well plate-based GelMA photo-crosslinking system with tunable hydrogel mechanical properties to regulate the PTH-mediated osteogenic fate.

Versatile and efficient regulation of the mechanical properties of the extracellular matrix is crucial not only for understanding the dynamic changes in biological systems, but also for obtaining precise and effective cellular responses in drug testing. In this study, we developed a well plate-based hydrogel photo-crosslinking system to effectively control the mechanical properties of hydrogels and perform high-throughput assays. We improved cell biocompatibility by using gelatin methacryloyl (GelMA) with a visible light photo-crosslinking method. Multiple cell-laden GelMA hydrogels were simultaneously and uniformly created using multi-arrayed 520 nm light-emitting diodes in a well plate format. The elastic modulus of the hydrogels can be widely adjusted (0.5-30 kPa) using a photo-crosslinking system capable of independently controlling the light intensity or exposure time for multiple samples. We demonstrate the feasibility of our system by observing enhanced bone differentiation of human mesenchymal stem cells (hMSCs) cultured on stiffer hydrogels. Additionally, we observed that the osteogenic fate of hMSCs, affected by the different mechanical properties of the gel, was regulated by parathyroid hormone (PTH). Notably, in response to PTH, hMSCs in a high-stiffness microenvironment upregulate osteogenic differentiation while exhibiting increased proliferation in a low-stiffness microenvironment. Overall, the developed system enables the generation of multiple cell-laden three-dimensional cell culture models with diverse mechanical properties and holds significant potential for expansion into drug testing.

Xanthone analogues as potent modulators of intestinal P-glycoprotein.

Intestinal P-glycoprotein (P-gp) is a limiting step for oral absorption of drugs. Therefore, P-gp inhibitors have been studied as enhancers of oral absorption of drugs that are P-gp substrates. We investigated the in vitro and in vivo P-gp inhibitory activity of synthesized xanthone analogues. With 3-(3-chloro-2-hydroxypropoxy)-1-hydroxy-9H-thioxanthen-9-one, compound 13, accumulation of daunomycin (DNM) increased 707% and efflux of DNM decreased 66% compared to DNM alone. Relative bioavailability (RB) of paclitaxel (PTX, 25 mg/kg) increased 2.5-fold after oral administration with 13 (5 mg/kg). In a xenograft animal model, oral administration of PTX (40 mg/kg) with 13 (10 mg/kg) significantly inhibited tumour growth and was more effective than intravenously administered PTX (10 mg/kg) alone. Therefore, the synthesized xanthone analogue 13 might have therapeutic benefits for oral absorption of P-gp substrate anticancer drugs.

Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues.

In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 microM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds.

New benzoxanthone derivatives as topoisomerase inhibitors and DNA cross-linkers.

We synthesized 12 benzoxanthone derivatives classified as three different groups based on the tetracyclic ring shapes and evaluated their pharmacological activities to find potential anticancer agents. In the cytotoxicity test, most compounds showed effective cancer cell growth inhibition against the HT29 and DU145 cell lines. Among the compounds tested, compound 19 was the most effective in the cancer cell lines tested. Compound 9 showed dual inhibitory activities against DNA relaxation by topoisomerases I and II. The% inhibition of compound 9 on topoisomerase I was comparable to that of camptothecin. Compound 9 efficiently blocked topoisomerase II function by almost threefold than etoposide at 20 microM. Compound 19 had selective topoisomerase II inhibitory activity at 100 microM. The DNA cross-linking test revealed that only compounds 8 and 19, which possess epoxy groups, cross-linked DNA duplex, while 14 did not. From the combined pharmacological results, we proposed that the target through which compound 19 inhibits cancer cell growth may be the DNA duplex itself and/or DNA-topoisomerase II complex.

Improved capacitance characteristics of electrospun ACFs by pore size control and vanadium catalyst.

Nano-sized carbon fibers were prepared by using electrospinning, and their electrochemical properties were investigated as a possible electrode material for use as an electric double-layer capacitor (EDLC). To improve the electrode capacitance of EDLC, we implemented a three-step optimization. First, metal catalyst was introduced into the carbon fibers due to the excellent conductivity of metal. Vanadium pentoxide was used because it could be converted to vanadium for improved conductivity as the pore structure develops during the carbonization step. Vanadium catalyst was well dispersed in the carbon fibers, improving the capacitance of the electrode. Second, pore-size development was manipulated to obtain small mesopore sizes ranging from 2 to 5 nm. Through chemical activation, carbon fibers with controlled pore sizes were prepared with a high specific surface and pore volume, and their pore structure was investigated by using a BET apparatus. Finally, polyacrylonitrile was used as a carbon precursor to enrich for nitrogen content in the final product because nitrogen is known to improve electrode capacitance. Ultimately, the electrospun activated carbon fibers containing vanadium show improved functionality in charge/discharge, cyclic voltammetry, and specific capacitance compared with other samples because of an optimal combination of vanadium, nitrogen, and fixed pore structures.

Synthesis of new xanthone analogues and their biological activity test--cytotoxicity, topoisomerase II inhibition, and DNA cross-linking study.

In this report, we prepared some 3-(2',3'-epoxypropoxy)xanthones and their epoxide ring opened halohydrin analogues, and evaluated their cytotoxicity and topoisomerase II inhibition activity using doxorubicin and etoposide as references, respectively. Another xanthone compound 9, 1,3-di(2',3'-epoxypropoxy)xanthone, was also synthesized and its DNA cross-linking property including other two biological activities investigated. The biological test results showed compound 9 possessed excellent cytotoxic and topoisomerase II inhibitory activity than other compounds tested. It also exhibited significant DNA cross-linking activities.

Three-dimensionally ordered macroporous carbons having walls composed of hollow mesosized spheres.

Three-dimensionally ordered macroporous carbons were prepared from bimodal polymer-silica colloidal crystals; the resulting carbons had interconnected macropores, and the walls of the macropores were composed of hollow mesosized spheres.