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We have engineered biomaterials that display nanoclusters of ligands that bind both integrin and syndecan-4 cell receptors. These surfaces regulate cell behaviors under static conditions including adhesion, spreading, actin stress fiber formation, and migration. The syndecan-4 receptors are also critical mediators of cellular mechanotransduction. In this contribution we assess whether this novel class of materials can regulate the response of cells to applied mechanical stimulation, using the shear stress imparted by laminar fluid flow as a model stimulus. Specifically, we assess endothelial cell detachment due to flow, cell alignment due to flow, and cell adhesion from the flowing fluid. A high degree of cell retention was observed on surfaces containing integrin-binding ligands or a mixed population of integrin- and syndecan-binding ligands. However, the presence of both ligand types was necessary for the cells to align in the direction of flow. These results imply that integrin engagement is necessary for adhesion strength, but engagement of both receptor types aids in appropriate mechanotransduction. Additionally, it was found that surfaces functionalized with both ligand types were able to scavenge a larger number of cells from flow, and to do so at a faster rate, compared to surfaces functionalized with only integrin- or syndecan-binding ligands. These results show that interfaces functionalized with both integrin- and syndecan-binding ligands regulate a significant range of biophysical cell behaviors in response to shear stress.

Recent studies show that cancer cells are sometimes able to evade the host immunity in the tumor microenvironment. Cancer cells can express high levels of immune inhibitory signaling proteins. One of the most critical checkpoint pathways in this system is a tumor-induced immune suppression (immune checkpoint) mediated by the programmed cell death protein 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1). PD-1 is highly expressed by activated T cells, B cells, dendritic cells, and natural killer cells, whereas PD-L1 is expressed on several types of tumor cells. Many studies have shown that blocking the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. In this review, we highlight a brief overview of the molecular and biochemical events that are regulated by the PD-1 and PD-L1 interaction in various cancers.

Colorectal cancer (CRC) is one of the most leading cancer deaths throughout the world. MiR-200c has been shown to have a critical role in cancer initiation and progression. In this study, we investigated the miR-200c expression in CRC tissues and its effects on CRC cell lines which were mediated by polycomb complex protein (BMI1). Quantitative reverse transcription polymerase chain reaction (QRT-PCR) and immunohistochemistry were used to detect miR-200c and BMI1 expression in tumor tissues from 38 patients with CRC and 38 normal colon tissues. HCT-116 and SW-48 cells were transfected by locked nucleic acid (LNA)-anti-miR-200c. Western blot analysis and real-time PCR were applied to determine the BMI1 protein and microRNA (miRNA) levels. The apoptosis was analyzed via annexin/propidium iodide staining, and cell invasion was evaluated by transwell assay. MiR-200c was markedly downregulated in CRC tissues, whereas the protein expression of BMI1 in CRC tissues was upregulated compared with normal colon tissues. In the colon cancer cell lines, transfection of LNA-anti-miR-200c increased BMI1 gene and protein expression as well as the cell invasion. Downregulation of miR-200c by LNA decreased the apoptotic cells. The results from this study revealed that miR-200c may have antitumor effects through inhibition of BMI1 expression.

Colorectal cancer (CRC) is one of the most lethal and rampant human malignancies in the world. Zerumbone, a sesquiterpene isolated from subtropical ginger, has been found to exhibit an antitumor effect in various cancer types. However, the effect of Zerumbone on the biological properties of CRC, including epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) has not been fully elucidated. Here, we investigated the inhibitory action of Zerumbone on the EMT process, CSC markers, and the β-catenin signaling pathway in the presence or absence of miR-200c. The effect of Zerumbone on HCT-116 and SW-48 cells viability was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of Zerumbone on EMT-related genes, CSCs markers, cell migration, invasion, sphere-forming, and β-catenin signaling pathway were explored. To evaluate the role of miR-200c in anticancer effects by Zerumbone, miR-200c was downregulated by LNA-anti-miR-200c. Zerumbone significantly inhibited cell viability, migration, invasion, and sphere-forming potential in HCT-116 and SW-48 cell lines. Zerumbone significantly suppressed the EMT and CSC properties as well as downregulated the β-catenin. Silencing of miR200c reduced the inhibitory effects of Zerumbone on EMT and CSCs in CRC cells. These data indicated that Zerumbone may be a promising candidate for reducing the risk of CRC progression by suppressing the β-catenin pathway via miR-200c. © 2018 Wiley Periodicals, Inc.

Objective: colorectal cancer (CRC) is one of the most common malignancies, associated with high rates of relapse. A notable challenge in treatment is low response rate to current therapies for advanced CRC. The miR-200c plays an essential role in tumor suppression by inhibiting epithelial–mesenchymal transition (EMT). Resveratrol, a natural compound found in red wine, reveals anti-cancer properties in several types of cancers such as CRC. The aim of current study was to evaluate the effects of resveratrol on proliferation, apoptosis, and invasion of HCT-116 cells and also expression of EMT-related genes in presences or absence of miR-200c. Methods: the effect of resveratrol on viability was examined by MTT assay. LNA-anti-miR-200c transfection of HCT-116 cells was carried out in a time dependent manner. Then, the expression of miR-200c and EMT-related genes were quantified by qRT-PCR. Further, expression of EMT-related proteins, apoptosis, and invasion were analyzed by Western blot, Annexin V/PI staining and scratch test, respectively. Results: resveratrol could significantly inhibit viability of HCT-116 cells. LNA-anti-miR-200c suppressed the endogenous miR-200c in transfected cells compared with the control. qRT-PCR and Western blot analysis of LNA-anti-miR-200c transfected cells revealed a considerable increase in vimentin and ZEB-1 expression, with a concomitant reduction in E-cadherin expression level. Migration of HCT-116 cells increased, and apoptosis significantly reduced in transfected cells. While, resveratrol could entirely reverse these changes by modulation of miR-200c expression. Conclusion: our findings revealed a major role of resveratrol in apoptosis, invasion, and switching of EMT to MET phenotype through upregulation of miR-200c in CRC. J. Cell. Biochem. 118: 1547–1555, 2017. © 2016 Wiley Periodicals, Inc.

We have developed green, efficient and powerful protocols for the preparation of 2,4,6-triarylpyridines and 1,8-dioxodecahydroacridines in the presence of Fe3O4@TiO2@O2PO2(CH2)2NHSO3H as a sulfonic acid-functionalized titana-coated magnetic nanoparticle catalyst under mild and solvent-free reaction conditions. These protocols furnished the desired products in short reaction times with good to high yields (20–40 min and 80–86% in the case of 2,4,6-triarylpyridines; 15–90 min and 80–93% in the case of 1,8-dioxodecahydroacridines). The final step of the mechanistic route in the synthesis of 2,4,6-triarylpyridines proceeds via an anomeric-based oxidation. Also, the nanomagnetic core–shell catalyst can be recycled and reused in both cases of the scrutinized one-pot multicomponent reactions with high turnover number and turnover frequency.

PURPOSE This study investigated whether the tubular occluding effect of oxalate desensitizer (OX) during adhesive cementation (three resin cements) influenced fracture resistance of teeth restored with adhesive inlays. MATERIALS AND METHODS Ninety intact maxillary premolars were randomly divided into 9 groups of 10 each. The two control groups were Gr 1, intact teeth and Gr 2, mesio-occlusodistal preparation only. In six experimental groups, the composite inlays were cemented with ED Primer II/Panavia F 2.0, Excite DSC/Variolink II, and One-Step Plus/Duolink according to manufacturers' instructions (Groups 3, 5, and 7, respectively) or with OX during cementation (Groups 4, 6, and 8, respectively). In Group 9, inlays were cemented with a resin cement without adhesive system. After thermocycling, fracture strength was tested. The data were analyzed using two-way and one-way ANOVA and LSD post hoc tests (α = 0.05). RESULTS Fracture resistance of the six groups were significantly affected by OX (p = 0.002) but not by the resin cement type (p > 0.05). The interaction of the two factors was statistically significant (p = 0.052). A statistically significant difference between all groups was found (p < 0.001). The mean fracture resistances (N) were: Gr1 = 1168 ± 157,(a) Gr2 = 360 ± 110,(d) Gr3 = 1026 ± 188,(b) Gr4 = 887 ± 143,(c) Gr5 = 1007 ± 132,(b) Gr6 = 810 ± 164,(c) Gr7 = 1033 ± 218,(a) Gr8 = 955 ± 147,(ab) Gr9 = 780 ± 86(c) (groups with the same superscript letter indicate statistical similarity). CONCLUSIONS Combining an OX with three resin cements had a significant negative effect on the fracture resistance of premolars restored with composite inlay cemented with Panavia F2.0 and Variolink II, but it had no significant effect when cemented with Duolink.

An efficient synthesis of quinoline derivatives is described via the reaction between ethyl chloropyruvate or alkyl 4-chloroacetoacetate and activated acetylenic compounds in the presence of nucleophilic form of isatin in water as the solvent. Nucleophilic form of isatin is produced from the reaction of isatin and triethylamin.

Quinoline derivatives (IV), (VI) are efficiently obtained in a one-pot three-component reaction of alkyl 4-chloroacetate or ethyl chloropyruvate and activated acetylenic compounds in the presence of the nucleophilic form of isatin in water.