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A new prenylated flavanonol, (2R,3R)-8-isopentenyl-5-methoxy-7,2′,4′-trihydroxyflavanonol (1) was isolated from the roots of Sophora flavescens. The structure was elucidated on the basis of spectroscopic data. Compound 1 exhibited moderate inhibition towards HeLa, HepG2, and HL-60 tumor cell lines at 14.3, 19.2, 31.5 μg/mL, respectively.

Background: Drug resistance is a major obstacle in chemotherapy for ovarian cancer, wherein the up regulation of drug-resistant genes plays an important role. The cytoplasmic polyadenylation element binding protein 4 (CPEB4) is an RNA binding protein that controls mRNA cytoplasmic polyadenylation and translation.Methods: The expression of CPEB4 in paclitaxel-resistant ovarian cancer cell lines and recurrent ovarian tumors relative to counterparts was determined by qRT-PCR, Western blotting and immunohistochemistry. The response to paclitaxel treatment was evaluated by cellular viability test and colony formation assay. RNA immunoprecipitation and poly(A) tail test were applied to examine the levels of RNA binding and cytoplasmic polyadenylation.Results: CPEB4 is elevated in paclitaxel-resistant ovarian cancer cells and recurrent ovarian tumors treated with paclitaxel-based chemotherapy. In addition, CPEB4 overexpression promotes paclitaxel resistance in ovarian cancer cells in vitro, and vice versa, CPEB4 knockdown restores paclitaxel sensitivity, indicating that CPEB4 confers paclitaxel resistance in ovarian cancer cells. Mechanistically, CPEB4 binds with the taxol (paclitaxel)-resistance-associated gene-3 (TRAG-3/CSAG2) mRNAs and induces its expression at a translational level. Moreover, CSAG2 expression is upregulated in paclitaxel-resistant ovarian carcinoma and cancer cell lines, and more importantly, siRNA-mediated CSAG2 knockdown overtly attenuates CPEB4-mediated paclitaxel resistance.Conclusion: This study suggests that the drug-resistant protein CSAG2 is translationally induced by CPEB4, which underlies CPEB4-promoted paclitaxel resistance in ovarian cancer in vitro. Thus, interfering CPEB4/CSAG2 axis might be of benefit to overcome paclitaxel-resistant ovarian cancer.

Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12-dimethylbenz(a)anthracene (DMBA)-treated mammary carcinogenesis in Sprague-Dawley (SD) rats and MCF-7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA-induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt-b5 and CYP450 ) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl-2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA-induced mammary cancer in SD animals and Michigan cancer foundation-7 mammary cancer cells.

The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models. MiR-137 was shown to control CRC cell proliferation, colony formation, migration and invasion and to control tumor growth and metastasis. We further confirmed the negative association between miR-137 and c-Met expression and thus validated this important oncogene as the target of miR-137 in CRC. In addition, we found a DNA methyl-CpG-binding protein, Mecp2, was up-regulated in ACS tissues via mRNA sequencing. Further experiment showed that miR-137 expression in CRC was subjected to epigenetic regulation mediated by Mecp2. We also confirmed c-Met expression can be up-regulated by silencing of miR-137 and suppressed by coexpression of Mecp2 and miR-137. These findings highlight the critical role of miR-137-c-Met nexus in CRC development and reveal Mecp2-regulated epigenetic silence causes the downregulation of miR-137 in colorectal adenoma and carcinoma.

Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.

Decorative chromium demand in the worldwide market is more than three times of hard chromium. But chromium plating processes has long been known to hazardous. The corrosion resistance of a nano-crystalline Sn-Co-X alloy intended as an alternative for decorative chromium has been studied. The corrosion resistance of Sn-Co-X are all better than trivalent chromium, hexavalent chromium, and it is more better than coarser gained Sn-Co alloy. The microstructures of Sn-Co-X alloy were analyzed by SEM, TEM, XPS and AES. The mechanism of its excellent corrosion resistance is described.

An experiment of a single direct methanol fuel cell (DMFC) was conducted at Fuel Cell laboratory of Tsinghua University, China in collaboration with University of Tsukuba, Japan. Influences of the anodic methanol solution's concentration, the cathodic air flow rate, and the cathodic oxygen gas flow rate on the single DMFC performance were investigated to optimize operating conditions of the fuel cell. The experimental results have shown that the single DMFC can reach the peak power density of 0.170 W/cm2 with the current of 0.515 A/cm2 under the condition of the concentration of methanol solution of 2M and the flow rate of oxygen gas of 80 mL/min.

To investigate the influence of Estradial (E(2)) at physiological concentration on mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α(HIF-α1) in bovine retinal vascular endothelial cells (BRECs) under different oxygen conditions.The mRNA expression of VEGF, HIF-1α in BRECs was studied by quantitative reverse-transcription PCR (qRT-PCR), and protein levels were assayed by Western Blot. Different concentrations of E(2) (10(-12), 10(-10), 10(-8) mol/l) and estrogen receptor antagonist Tamoxifen (10(-7) mol/l) were added into the cell culture medium of different groups, while the phosphate-buffered saline (PBS) was added in the control group instead. Culture conditions were set to be under normoxia and hypoxia. The results of each group were detected after 8 hours and 24 hours.(1) Under hypoxia, gene expression of VEGF, HIF-1α in BRECs increased more than that of the control group (P 0.05). There is evident positive correlation between the mRNA and protein levels of VEGF and HIF-1α (r = 0.82). (2) Treated with 10(-8) mol/l E(2,) the expression of VEGF mRNA was increased in a time-dependent manner (P 0.05). Treated with the indicated to concentrations of E(2) (10(-12 ∼ -8) mol/l) under normoxia for twenty-four hours, the mRNA expression of VEGF in BRECs was increased in a dose-dependent manner (P 0.05), whereas E(2) did not influence the mRNA expression of HIF-1α (P 0.05). (3) Under hypoxia , E(2) reduced the mRNA and protein levels of HIF-1α and VEGF in a concentration-dependent manner (P 0.05), and the decrease developed in a time-dependent manner (P 0.05). (4) An overdose of tamoxifen (10(-7) mol/l) reversed the effect of E(2) (10(-8) mol/l) (P 0.05).E(2) increases the gene expression of VEGF in BRECs under normoxia, whereas E(2) reduces the gene expression of VEGF in BRECs through HIF-1α under hypoxic conditions in a dose-dependent and time-dependent manner. The contrasting effect of E(2) on mRNA expression of VEGF may play a prophylactic role in retinopathy of prematurity (ROP).

Chronic cerebral hypoperfusion (CCH) has been commonly associated with Alzheimer's disease and other types of dementia, but therapies that can improve cerebral blood flow displayed little effect on impaired cognition. Epigenetic intervention with histone deacetylase inhibitors, such as sodium butyrate (SB), on the other hand has been shown to improve cognition in several animal models of dementia. To investigate the effect of SB on cognitive impairment induced by CCH in rats, adult male SD rats were given intraperitoneal injections of SB at a daily dose of 840mg/kg for 4weeks, from the 29th day after permanent occlusion of bilateral common carotid arteries (2VO). Learning and memory were assessed by Morris water maze and novel object recognition. Following behavioral tests, western blotting of histone acetylation, of transcription factors, of neuronal/synaptic proteins, were performed using rat hippocampus and cortex. The data showed that SB treatment alleviated hippocampal dependent spatial learning disability in 2VO rats, and altered HDAC1/2 mRNA level, histone H4 acetylation and Nrf2 transcriptional activation in rat hippocampus. Accordingly, cognition-protective effect of SB appeared to be partially mediated by enhancing histone acetylation and hence by facilitating the transcription of Nrf2 downstream genes in the hippocampus. Thus, SB might be considered for putative treatment for CCH-related cognitive impairment.

An Indonesian low-rank coal, Adaro, was hydrothermally treated at 200-350°C in an autoclave. The raw and treated coals have been subjected to several analyses which include hygroscopicity, the content of oxygenic functional groups, FTIR spectrum, and specific surface area. When the coal is hydrothermally treated, the hygroscopicity of coal remarkably decreases. The content of carboxyl group in coal greatly decreases as the heat treatment temperature (HTT) is raised. From FTIR analysis, the methyl/methylene ratio in coal somewhat increases, especially when the coal is treated at 350°C; while the aromaticity of coal is enhanced a little. Due to the hydrothermal treatment, the ignition temperature (T i ) shifts to a high temperature; whereas the temperature, at which the maximum combustion rate occurs (T m ), is not so changed. The change in the properties of coal and the combustion characteristics is discussed.