Discovery of 4-benzoylamino-N-(prop-2-yn-1-yl)benzamides as novel microRNA-21 inhibitors.

MicroRNA-21, as an oncogenic miRNA, has caught great attention for medicinal chemists to develop its novel inhibitors for cancer therapy. In the present study, we designed 4-benzoylamino-N-(prop-2-yn-1-yl)benzamides as miR-21 inhibitor candidates on the basis of scaffold hopping. Eighteen compounds were synthesized. The inhibitory activities of synthesized compounds against the expression of miR-21 were evaluated using stem loop RT-qPCR and compound 1j was discovered as the most potent compound, which displayed a time and concentration dependent inhibition manner. In addition, various functional assays such as the expression of miR-21 target gene detected by Western blotting and the cell growth and apoptosis detected by flow cytometric analysis were checked in Hela (human epithelioid cervix carcinoma) and U-87 MG (human glioblastoma) cells to confirm its activity. The results indicate that compound 1j can enhance apoptosis, retard proliferation, and up-regulate PDCD4, a target protein of miR-21. In addition, the compound 1j does not influence the expression of multiple miRNAs and the genes that participate in miRNA universal biosynthesis pathway. These results strongly support the assumption that title compounds can serve as a small molecule inhibitor of miR-21.

Postsynthetic Modification of ZIF-8 Membranes via Membrane Surface Ligand Exchange for Light Hydrocarbon Gas Separation Enhancement.

The ability to tailor the pore structure of metal-organic framework (MOF) membranes enables synthesis of new or modified MOF membranes with enhanced separation characteristics. This work employs a modified version of solvent-assisted ligand exchange, termed membrane surface ligand exchange (MSLE), to modify the pore structure of zeolitic imidazolate framework-8 (ZIF-8) membranes. This paper is the first to perform a time-based, ex situ characterization and gas permeation study of ZIF-8 MSLE with 5,6-DBIM (DBIM, dimethylbenzimidazole) to effectively narrow the ZIF-8 pores, enhance light hydrocarbon gas-phase separations, and give insight into the exchange mechanism with respect to time and temperature. The results show that relatively fast exchange kinetics occur mainly at the outer surface of the ZIF-8 membrane during the initial 30 min of exchange and enables significant (40-70%) increases in propylene/propane selectivity with minimal (10-20%) propylene permeance losses for the modified ZIF-8 membranes. We postulate as the reaction time proceeds, the ligand-exchange rate slows as the DBIM linker diffuses into the ZIF-8 membrane beyond the external surface, exchanges with the original linker, disrupts the original framework's crystallinity, and then increases long-range order/crystallinity as the reaction proceeds. The H2/C2 separation factor increases with increased 5,6-DBIM content in the ZIF-8 framework which is facilitated by increased MSLE time and reaction temperature.

Self-Assembled Monolayer of Metal Oxide Nanosheet and Structure and Gas-Sensing Property Relationship.

Semiconducting 2D metal oxides have attracted great research interests for gas-sensing applications because of their considerable specific surface area and highly homogeneous surface. Developing a method for fabricating thin films of 2D metal oxides is crucial for minimizing the negative effects on sensing performance caused by slow diffusion. In this work, a simple, versatile, and highly reproducible self-assembly method is developed for fabricating monolayer film sensors made from metal oxide nanosheets with much superior sensing performance compared with their thick film counterparts. To prepare the monolayer film sensors, a monolayer film of metal oxide nanosheets, self-assembled at the air-water interface, is transferred onto a sensor substrate. The CuO monolayer sensors prepared with this self-assembly method show much improved gas sensitivity (sensor signal: 350% vs 100% at 5 ppm of H2S) and faster response and recovery rate (τres: 20 s vs 110 s; τrec: 120 s vs 320 s) than the thick film sensors prepared from the same sensing material. The enhanced sensing performance demonstrated by the monolayer film of CuO nanosheets is explained quantitively with a modified coupled reaction-diffusion model. Similar enhancement on gas-sensing performance is also observed for the ZnO-nanosheet-based monolayer sensors prepared by the same self-assembly method.

Long-term observation for osseointegriation of calcium 'phosphate sol-gel coating on Ti-6Al-4V implants.

OBJECTIVE: To observe the long-term impact of calcium phosphate (CaP) sol-gel coating on bone growth around porous-surfaced implant. METHODS: The porous-surfaced Ti-6Al-4V implants were prepared with the addition of a thin film of CaP sol-gel coating, and implanted into the tibiae of 8 rabbits, each with two implants. Implanted sites were allowed to heal for 2, 8, 12, and 24 weeks, after which specimens were obtained for scanning electron microscope analysis using the freeze-fracture technique. RESULTS: The sol-gel coated implants recovered by freeze-fracture technique showed extensive bone growth from the endosteum along the implant surface. The bone was in direct contact with the CaP layer. The cement line-like layer was clearly demonstrated to be an intervening electron dense afibrillar layer between the CaP coat and the overlying newly deposited bone. The stability and osseointegration of the porous-surfaced implants seemed not to be affected by the osteoclastic resorption of CaP layer occurred during 24 weeks of healing. CONCLUSION: Based on the findings in the long-term observation, the addition of a thin layer of CaP promotes an extensive osseointegrated interface between the porous-surfaced Ti-6Al-4V implants and the newly deposited bone.

Cytotoxicity study of a novel implant material modified by microarc oxidation.

This study examined the cytotoxicity of a new implant material modified by microarc oxidation technique. Cells on different surfaces of the implant were evaluated 2, 4 and 6 days after treatment. The results showed that cell attachment, cell morphology, and cell proliferation were influenced by the different surface treatments, and a significant increase in the osteoblast cell activity was observed on the porous MAO-Ti coating. Our results suggest that the porous MAO-Ti surface has a better biocompatibility and electrochemical performance than pure titanium surface.

Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions.

OBJECTIVE: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats. METHODS: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane, and then treated with MTX or BSO. Arthritis severity was evaluated macroscopically and microscopically. Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The clinical arthritis severity was decreased after MTX treatment, while the BSO groups did not show significant changes compared with the disease group. The plasma NO level of the MTX group was significantly decreased compared with the disease group, but the BSO groups showed no difference from the disease group in plasma NO levels. The interferon-γ (IFN-γ) and interleukin-17A (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX group, but only showed a declining trend in the BSO groups compared with the disease group. Neither MTX nor BSO had an effect on the mRNA expressions of IL-4, transforming growth factor ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in the spleen. CONCLUSIONS: MTX, but not BSO, can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.