Immunomodulatory Effect of Flavonoids of Blueberry (Vaccinium corymbosum L.) Leaves via the NF-κB Signal Pathway in LPS-Stimulated RAW 264.7 Cells.

OBJECTIVE: This study aimed to explore the immunoregulatory effect of flavonoids of blueberry (Vaccinium corymbosum L.) leaves (FBL). METHODS: The flavonoids of blueberry leaves were prepared with 70% ethanol and were identified by ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-Tof-MS). The immunoregulatory effect and possible regulatory mechanisms of FBL were investigated in lipopolysaccharide- (LPS-) induced RAW 264.7 cells. RESULTS: According to the results of UPLC/Q-Tof-MS, nine flavonoids of blueberry leaves were identified. FBL showed a significant reduction in the production of TNF-α in LPS-stimulated RAW 264.7 cells. FBL significantly decreased the expression of NF-κB p65 and P-NF-κB p65 in LPS-induced RAW 264.7 cells in a dose-dependent manner. CONCLUSION: Our study showed the immunoregulatory effect of FBL through the suppression of TNF-α via the NF-κB signal pathway.

Design, synthesis and biological evaluation of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives.

Based on our previous work, a series of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that some compounds possessed significant antiproliferative activities against four cancer cell lines, HepG2, HCT116, PC-3, and Hela. Particularly, the most promising compound 8d displayed 184-, 18-, and 17-fold improvement compared to fluorouracil in inhibiting HCT116, Hela and PC-3 cell proliferation with IC50 values of 0.37, 2.94, and 31.31µM, respectively. Most interestingly, the compound did not affect the normal human embryonic kidney cells, HEK-293. Moreover, mechanistic investigation showed that the representative compound 8d induced apoptosis and blocked cell cycle in G2/M phase in Hela cells in a dose-dependent manner. These findings suggest that compound 8d may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.

Flk-1⁺Sca-1⁻ mesenchymal stem cells: functional characteristics in vitro and regenerative capacity in vivo.

OBJECTIVES: Mesenchymal stem cells (MSCs) represent a powerful tool in regenerative medicine because of their differentiation and migration capacities. We aimed to investigate the possibility of Flk-1(+)Sca-1(-) mesenchymal stem cells (Flk-1(+)Sca-1(-) MSCs) transplantation to repair erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED). METHODS: In this study, we isolated Flk-1(+)Sca-1(-) MSCs from bone marrow (bMSCs). Then, newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine for the purpose of tracking endogenous Flk-1(+)Sca-1(-) MSCs. Eight weeks later, 8 of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group) while another 8 rats were subject to Flk-1(+)Sca-1(-) MSCs treatment (DM+MSC group). All rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology. RESULTS: Flk-1(+)Sca-1(-) MSCs could differentiate into skeletal muscle cells and endothelial cells in vivo and in vitro. Engrafted Flk-1(+)Sca-1(-) MSCs were shown to home to injured muscle, participate in myofibers repair and could partially reconstitute the sarcolemmal expression of myocardin and ameliorate the level of related specific pathological markers. CONCLUSION: Flk-1(+)Sca-1(-) MSCs could be used in the treatment erectile function in diabetes mellitus associated erectile dysfunction by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis.

Design, synthesis and biological evaluation of novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines bearing furan and thiophene nucleus.

Twenty-six novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines containing furan and thiophene nucleus were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that most of the compounds showed moderate to potent antiproliferative activities against four cancer cell lines, PC-3, HepG2, A549, and MCF-7. Particularly, compound 32 showed eleven-, three-, and two-fold improvement compared to positive control fluorouracil in inhibiting HepG2, PC-3, and A549 cell proliferation with IC50 values of 5.09, 3.70 and 12.74 µM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 32 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. These encouraging results should provide important information for the development of new anticancer agents.