Organ-on-a-chip (OoC) systems allow the generation of microphysiological tissue models that can recapitulate key biological processes in healthy and diseased states. OoC bone models provide valuable tools to study crosscellular interactions that take place in bone-related processes. Although few bone-on-a-chip models have been proposed, structural and biological hierarchy to establish a functional unit is often lacking. Herein, a functional OoC-based 3D bone co-culture model is reported. This model comprises a highly porous β-tricalcium phosphate (TCP) based scaffold that is seeded with primary osteoblast and osteoclast precursors. This engineered construct is formed and cultured dynamically inside an OoC platform for up to 21 days and exhibits a dense extracellular matrix (ECM). Further, cultured constructs are ectopically implanted in C57BL/6 mice for 8 weeks, then histological and tartrate-resistant acid phosphatase (TRAP) analyses are carried out. These results demonstrate that both bone deposition and resorption processes are present in the bioengineered model. This study also has implications for understanding complex cellular cross-talks occurring in the bone remodeling process.
The synthesis, docking study, and investigation of the anticancer activities of some coumarin derivatives containing the triazole ring are reported in this study. The newly synthesized compounds were screened for their in vitro anticancer activity against the cell lines CRL5807 (human bronchioalveolar carcinoma), CRL5826 (human squamous cell carcinoma), MDA‐MB231 (human breast cancer cells), HTB177 (human lung cancer), PC‐3 (human prostate adenocarcinoma), PANC‐1 (human pancreatic cancer cells), used as cancer cells, and CCD34Lu (normal human lung fibroblasts), used as a healthy cell line. Cytotoxicity effects of the samples were determined by the MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay. In silico studies were also performed to explore the binding interactions of the molecules.
In this study, novel 2-substituted benzimidazoles molecules having triazole, thiadiazole, and oxadiazole rings were synthesized and were evaluated by anticancer, antioxidant/oxidant status, genotoxicity, and antiangiogenesis assays.Anticancer activity of the compounds was determined by MTT (0.5, 5, and 50 µ g/mL) and lactate dehydrogenase (LDH) release assays against human prostate and breast cancer cells. Oxidative status of cells was elicited by total oxidative stress and total antioxidant capacity methods. Chick chorioallantoic membrane assay was used to evaluate the antiangiogenic activity. Genotoxicity was evaluated by the sister chromatid exchange (SCE) and micronucleus (MN) tests in lymphocyte cultured human blood. Our results showed that some of the compounds synthesized had significant antiproliferative activity against both cancer cell lines (between 4.54 ± 0.35 and 20.17 ± 3.15 µ g/mL), with higher inhibition of the breast cancer, and caused inhibition of LDH release with a linear correlation to MTT results. Moreover, the 5 µ g/mL dose of these molecules led to an increase in antioxidant levels. Compounds had antiangiogenic effectiveness in a dose-dependent manner. Additionally, all of the compounds did not affect SCE and MN levels compared to controls.In conclusion, these newly synthesized molecules can be a resource of new anticancer agents with their nongenotoxic, antiproliferative, and antiangiogenic properties.
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