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A polymer gel is a soft and wet material capable of undergoing large deformation. A deformed gel, in turn, changes its chemical potential, behaving as an energy transducer. Thus, a polymer gel shows a variety of stimuli-responsive actions, responding to external environmental changes. In this article unique electrical, thermal, and chemical responses of polymer gels are described. Recently observed frictional specificities of gels are also briefly introduced.

Luminescent labeling and magnetic separation are two important bio-techniques. Materials with the combined function of these two properties have many applications in biomedical science. The common strategy of producing such materials is to anchor magnetic nanoparticles and organic fluorophores to two types of molecules that can interact with each other. [1] Recently, several methods have been developed by using QDs and magnetic nanoparticles, [2] and encapsulating both particles in polymer microcapsules. [3] However, the development of bifunctional nanoparticles with higher structural stability and more specific binding is instantly desired. In this work, we propose a new strategy to fabricate bifunctional nanospheres (BFNs) with both fluorescence and magnetism, [4] and further to construct trifunctional nanospheres (TFNs), which show capacity of capture and separation of specific cancer cells.The BFNs were prepared by embedding fluorescent CdSe/ZnS QDs and magnetic nano-g-Fe 2 O 3 into hydrazinized styrene/acrylamide (H 2 N-St-AAm) copolymer nanospheres simultaneously. In order to ensure that both the QDs and magnetic nanoparticles are embedded, the particles must be small and well dispersed in an identical solvent. Therefore hydrophobic QDs and ferromagnetic nanoparticles were prepared. A new method for the preparation of nano-Fe 2 O 3 through a high-temperature decomposition route was then developed based on a reported method. [5] Xray diffraction (XRD) indicated that the crystal structure of the product was cubic g-Fe 2 O 3 (Figure 1 a) rather than Fe 3 O 4 . [5] It is because our experiments were carried out in air and in the absence of 1,2-hexadecanediol, which may reduce iron cations. Transmission electron microscopy (TEM) results indicate that the particles have an average particle size smaller than 20 nm with a narrow size distribution and are well dispersed (Figure 1 b).St-AAm copolymer nanospheres were synthesized from styrene and acrylamide by a modified method of emulsifierfree polymerization. [6] The size of the spheres can be changed from 50 to 500 nm by adjusting the concentration of raw materials and the dosage of the trigger. Scanning electron microscopy (SEM) images imply that the surface of the spheres is mesoporous, thus providing an entry route for nanoparticles ( Figure 2). As the scheme is emulsifier-free, the surface is relatively clean and convenient for conjugating with other molecules.The hydrophilic groups of the polymer tend to be located towards the outer surface of the nanospheres, while the hydrophobic moieties are found at the interior, leading to the formation of hydrophobic hollow cavities, since the nanospheres are synthesized in an aqueous solution. Both hydrophobic QDs (3-6 nm) and nano-g-Fe 2 O 3 (5-20 nm) were embedded in a weakly polar organic solvent. As shown in Figure 2, the particles are widely distributed inside the nanospheres with a relatively clean surface. It is notice-Figure 1. a) XRD pattern indexed onto a face-centred-cubic unit cell with a = 0.835 nm; b) TEM...

The aim of this study was to compare three methods of detection of apoptotic cells: (1) the method based on elution of low molecular weight DNA from the ethanol fixed cells followed by cell staining with DAPI (diamidino‐2–phenylindole) or propidium iodide as the DNA fluorochromes, (2) the method of in situ labeling of DNA strand breaks with biotinylated dUTP, utilizing exogenous terminal deoxyribonucleotide transferase, and (3) the method of analysis of DNA denaturation in situ using acridine orange to differentially stain denatured and doublestranded DNA sections following cell exposure to 0.1 M HCl. Cells of the human promyelocytic HL‐60 line, treated in vitro with the DNA topoisomerase I inhibitor camptothecin, which selectively triggers apoptosis of S‐phase cells, were chosen as a model. The method based on analysis of changes in DNA denaturability was the most sensitive in terms of detection of the earliest changes in chromatin of cells undergoing apoptosis; the increased sensitivity of DNA to denaturation in Sphase cells was measured as early as 100 min after addition of camptothecin. DNA cleavage, assayed either by the univariate measurement of DNA content following extraction of low molecular weight DNA, or by labeling DNA strand breaks with biotinylated dUTP, was detected in S‐phase cells after 120 min incubation with camptothecin. The percentage of apoptotic cells at the late stage of apoptosis, the kinetics of cell transition to apoptosis, and kinetics of the loss of S phase cells were all essentially similar when measured by any method. All three methods can be used to estimate the cell cycle phase specificity of apoptosis, although the method based on DNA strand labeling with biotinylated dUTP by terminal deoxynucleotidyl transferase has the advantage of making it possible to estimate the cell cycle distribution of both the apoptotic and unaffected cell populations. The latter method also appears to be the most specific in terms of detection of apoptosis. © 1994 Wiley‐Liss, Inc.

Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.

PurposeMacrophages play critical roles in inflammation and wound healing and can be divided into two subtypes: classically activated (M1) and alternatively activated (M2) macrophages. Macrophages also play important roles in regulating iron homeostasis, and intracellular iron accumulation induces M1‐type macrophage polarization which provides a potential approach to tumor immunotherapy through M2 tumor‐associated macrophage repolarization. However, the mechanisms underlying iron‐induced M1 polarization remain unclear.MethodsWestern blotting, qRT‐PCR, and flow cytometry were used to detect the polarization indexes in RAW 264.7 murine macrophages treated with iron, and Western bloting and qRT‐PCR were used to detect p21 expression. The compound 2,7‐dichlorofluorescein diacetate was used to measure reactive oxygen species (ROS) levels in macrophages after iron or N‐acetyl‐l‐cysteine (NAC) treatment. The p300/CREB‐binding protein (CBP) inhibitor C646 was used to inhibit p53 acetylation, and Western bloting, qRT‐PCR, and immunofluorescence were used to detect p53 expression and acetylation. BALB/c mice were subcutaneously injected with H22 hepatoma cells, and macrophage polarization status was investigated after tail intravenous injection of iron. Immunohistochemical staining was used to evaluate the protein expression of cluster of differentiation 86 (CD86) and EGF‐like module‐containing mucin‐like hormone receptor‐like 1 (F4/80) in the subcutaneous tumors.ResultsIron overload induced M1 polarization by increasing ROS production and inducing p53 acetylation in RAW cells, and reduction in ROS levels by NAC repressed M1 polarization and p53 acetylation. Inhibition of acetyl‐p53 by a p300/CBP inhibitor prevented M1 polarization and inhibited p21 expression. These results showed that high ROS levels induced by iron overload polarized macrophages to the M1 subtype by enhancing p300/CBP acetyltransferase activity and promoting p53 acetylation.

BackgroundFocal adhesion plays an essential role in tumour invasiveness and metastasis. Hippo component YAP has been widely reported to be involved in many aspects of tumour biology. However, its role in focal adhesion regulation in breast cancer remains unexplored.MethodsTissue microarray was used to evaluate YAP expression in clinical breast cancer specimens by immunohistochemical staining. Cell migration and invasion abilities were measured by Transwell assay. A cell adhesion assay was used to measure the ability of cell adhesion to gelatin. The focal adhesion was visualized through immunofluorescence. Phosphorylated FAK and other proteins were detected by Western blot analysis. Gene expression profiling was used to screen differently expressed genes, and gene ontology enrichment was performed using DAVID software. The gene mRNA levels were measured by quantitative real-time PCR. The activity of the THBS1-promoter was evaluated by dual luciferase assay. Chromatin immunoprecipitation (ChIP) was used to verify whether YAP could bind to the THBS1-promoter region. The prediction of potential protein-interaction was performed with the String program. The ChIP sequence data of TEAD was obtained from the ENCODE database and analysed via the ChIP-seek tool. The gene expression dataset (GSE30480) of purified tumour cells from primary breast tumour tissues and metastatic lymph nodes was used in the gene set enrichment analysis. Prognostic analysis of the TCGA dataset was performed by the SurvExpress program. Gene expression correlation of the TCGA dataset was analysed via R2: Genomics Analysis and Visualization Platform.ResultsOur study provides evidence that YAP acts as a promoter of focal adhesion and tumour invasiveness via regulating FAK phosphorylation in breast cancer. Further experiments reveal that YAP could induce FAK phosphorylation through a TEAD-dependent manner. Using gene expression profiling and bioinformatics analysis, we identify the FAK upstream gene, thrombospondin 1, as a direct transcriptional target of YAP-TEAD. Silencing THBS1 could reverse the YAP-induced FAK activation and focal adhesion.ConclusionOur results unveil a new signal axis, YAP/THBS1/FAK, in the modulation of cell adhesion and invasiveness, and provides new insights into the crosstalk between Hippo signalling and focal adhesion.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0850-z) contains supplementary material, which is available to authorized users.