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Human hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific sulfapyridine HPMA (HPMA: N-(2-hydroxypropyl methacrylamide)) copolymer (sulfapyridine: SPD) conjugates, nonspecific HPMA copolymer conjugates, and DTPA are described in this study. The poly (HPMA)-SPD-DTPA (DTPA: diethylenetriaminepentaacetic acid), poly(HPMA)-DTPA, and DTPA conjugates were radiolabeled with the radionuclide 99mTc and tested for uptake by cultured H22 cells. The cellular accumulation of poly(HPMA)-SPD-DTPA-99mTc complex was found to be time-dependent. The poly(HPMA)-SPD-DTPA-99mTc tracer exhibited rapid uptake kinetics in cell culture with a t1/2 of ~5 min. The uptake of poly(HPMA)-SPD-DTPA-99mTc was significantly higher than'that of poly(HPMA)-DTPA- 99mTc, indicat-ing that the uptake of the poly(HPMA)-SPD-DTPA-99mT was active binding. The uptake of poly(HPMA)-DTPA-99mTc was significantly higher than that of DTPA- 99mTc, suggesting that the uptake of the poly(HPMA)-DTPA-99mT was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p< 0.001) tumor localization for poly(HPMA)-SPD-DTPA-99mTc (4.98±0.48%ID/g [per-centage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-99mTc (2.69 ±0.15% ID/g) and DTPA-99mTc (0.83±0.03%ID/g). Moreover, higher T/B for poly (HPMA)-SPD-DTPA-99mTc indicated reduced extravazation of the targeted polymeric conjugates in normal tissues. Specific molecular targeting and nonspecific vascular permeability are both significant in the relative tumor localization of poly(HPMA)-SPD-DTPA- 99mTc. Extravascular leak in nonspecific organs appears to be a major factor in reducing the T/B for the sulfapyridine molecules. Thus, the poly(HPMA)-SPD-DTPA is expected to be used as the potential macromolecular targeting carrier for hepatoma carcinoma in mice. [ABSTRACT FROM AUTHOR]

To develop a theranostic agent for diagnostic imaging and treatment of hepatocellular carcinoma (HCC), poly(HPMA)-APMA-DTPA-99mTc (HPMA: N-(2-hydroxypropyl methacrylamide; APMA: N-(3-aminopropyl)methacrylamide; DTPA: diethylenetriaminepentaacetic acid) and DTPA-99mTc were synthesized and characterized, and their HCC targeting was tested by in vitro cellular uptake and in vivo tumor imaging in this study. Radioactivity of HCC cells incubated with poly(HPMA)-APMA-DTPA-99mTc was significant higher (16.40%) than that of the cells incubated with DTPA-99mTc (2.98%). Scintigraphic images of HCC in mice obtained at 8 h after injection of poly(HPMA)-APMA-DTPA-99mTc showed increased radioactivity compared with that in mice injected with DTPA-99mTc. The results of postmortem tissue radioactivity assay demonstrated higher radioactivity of HCC tumor tissues (2.69 ± 0.15% ID/g) from the tumor-bearing mice injected with poly(HPMA)-APMA-DTPA-99mTc compared with that of HCC tumor tissues in the tumor-bearing mice injected with DTPA-99mTc (0.83 ± 0.03 %ID/g), ( P <0.001). These results first directly confirm the significant passive hepatocellular tumor targeting of HPMA copolymer. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 [ABSTRACT FROM AUTHOR]

A basic ionic liquid, 1-butyl-3-methyl imidazolium hydroxide ([bmim]OH), efficiently promotes a one-pot, three-component condensation of aromatic aldehydes, malononitrile or ethyl cyanoacetate, and 2-hydroxy-1,4-naphthoquinone to produce 4-aryl-5,10-dihydro-4 H-benzo[ g]chromene-5,10-dione derivatives in high yields at room temperature. This reaction does not involve any hazardous organic solvent and toxic catalyst. The ionic liquid is recovered and recycled for subsequent reactions. Moreover, this protocol has the advantages of easy work-up, short reaction time, high yields, and environmentally benign procedure compared with the reported methods. J. Heterocyclic Chem., (2011). [ABSTRACT FROM AUTHOR]

Hydrogels are widely used in drug delivery systems and outperform traditional biomaterials. However, it is still a challenge to develop targeted antitumor function in hydrogels with good stability and strong mechanical properties for drug carriers. Herein, we constructed novel composite polysaccharide drug-loaded hydrogels (FA–ASA–FG/MTX) from fenugreek gum (FG) and sodium alginate conjugated with folate (FA–ASA). The interpenetrating entanglement between FG and sodium alginate could improve the mechanical properties of the composite hydrogels. Additionally, the introduction of folate endowed the hydrogels with tumor-targeting properties. The composite hydrogels were determined to have a porous structure, water absorption, good stability and a sustained release effect by the determination of load ratio, rheological characterization, swelling behavior and drug release rate. Notably, the inhibition rate of the composite hydrogels against tumors was evaluated on HepG2 cells in vitro, which confirmed the targeting function of FA–ASA–FG/MTX with dose- and time-dependent behavior. Our results indicated that the composite hydrogels were a promising targeted anti-tumor agent and represented potential advances in the field of tumor-targeted drug delivery. [ABSTRACT FROM AUTHOR]

Porcine-induced pluripotent stem cells (piPSCs) are of great significance to animal breeding and human medicine; however, an important problem is that the maintenance of piPSCs mainly depends on exogenous expression of pluripotent transcription factors (TFs), and germline transmission-competent piPSCs have not yet been successfully established. In this study, we explore the defect of epigenetic reprogramming during piPSCs formation, including chromatin accessibility, DNA methylation, and imprinted gene expression, with high-throughput sequencing (ATAC-seq, WGBS, RNA-seq, and Re-seq) methods. We found the somatic features were successfully silenced by connecting closed chromatin loci with downregulated genes, while DNA methylation has limited effects on somatic silence. However, the incomplete chromatin remodeling and DNA demethylation in pluripotency genes hinder pluripotent activation, resulting in the low expression of endogenous pluripotency genes. In addition, the expression of potential imprinted genes was abnormal, and many allelic-biased expressed genes in porcine embryonic fibroblasts (PEFs) were erased, accompanied by establishment of new allelic-biased expressed genes in piPSCs. This study reveals the aberrant epigenetic reprogramming during dox-dependent piPSCs formation, which lays the foundation for research of porcine-iPSC reprogramming and genome imprinting. [ABSTRACT FROM AUTHOR]

Xanthohumol (XN) is the major prenylated chalcone of the female inflorescences (cone) of the hop plant (Humulus lupulus). It is also a constituent of beer, the major dietary source of prenylated flavonoids. It has shown strong antitumorigenic activity towards various types of cancer cells. In the present study, we show the impact on human hepatocarcinoma cell line HepG2 cell and potential adverse effects on rat primary hepatocytes. Cell growth/viability assay (MTT) demonstrated that HepG2 cells are highly sensitive to XN at a concentration range of 25-100 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of Annexin Ⅴ-FITC, we show that XN at a concentration of 25 μM induced apoptosis in HepG2. Further evidence that XN kills HepG2 by inducing apoptosis was provided by the impact of XN on the cleavage of PARP-1 and caspases-3. In contrast, XN concentrations up to 100 μM did not affect viability of primary rat hepatocytes in vitro, meanwhile, XN did not induce the apoptosis of primary rat hepatocytes in vitro. In summary, our data provide a rationale for clinical evaluation of XN for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]