Aberrant methylation and downregulation of sall3 in human hepatocellular carcinoma

AIM: To investigated whether sall3 transcription was regulated by promoter CpG island hypermethylation in hepatocellular carcinoma (HCC). METHODS: The cell lines Huh7, HepG2, SK-HEP1, SM-MC7721, Bel7402, QGY7703 and a cohort of 38 HCC tissue specimens and corresponding nontumorous tissues were subjected to analysis for sall3 promoter CpG island methylation and mRNA transcription. sall3 promoter CpG island methylation levels were determined using the MassARRAY platform and mRNA transcription levels of the gene were detected by quantitative realtime polymerase chain reaction.RESULTS: The levels of sall3 mRNA were decreased by more than twofold in 33 of 38 tumor tissues compared to adjacent noncancerous tissues. Among these 33 tumor tissues with lower levels of sall3 mRNA, 24 showed higher levels of methylation. Based on these results, we hypothesized that the decrease in sall3 mRNA transcription level was likely due to promoter CpG island hypermethylation. Changes in sall3 mRNA transcription and promoter CpG island methylation were determined in the above six cell lines after treatment with 0, 0.1, 0.5 and 2.5 mmol 5-aza-2-deoxycytidine, a demethylating agent. Promoter CpG island methylation levels de- creased in a dose-dependent manner in all six cell lines, while the mRNA transcription level increased dose-dependently in Huh7, HepG2, SK-HEP1 and SMMC7721 cells and irregularly in Bel7402 and QGY7703 cells. CONCLUSION: These results indicated that promoter CpG island hypermethylation contributes to the downregulation of sall3 mRNA transcription in HCC.

Targeting self-enhanced ROS-responsive artesunatum prodrug nanoassembly potentiates gemcitabine activity by down-regulating CDA expression in cervical cancer

Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs(systemic distribution and side effects).It's noted the conversion of gemcitabine(GEM)to inactive ingredients under the action of cytidine deaminase(CDA)during metabolism in vivo limits its clinical effect.A high level of reactive oxygen species(ROS)results in a high level of oxidative stress in tumor cells,which changes the expression of CDA and optimizes the metabolism of GEM in vivo and overcome drug resistance.In this study,the ROS responsive and ROS self-supplied prodrug of artemisia(ART)-thioacetal bond(TK)-GEM was synthesized and self-vectors based on ART-TK-GEM(TK@FA NPs)was prepared by using nano precipitation.ROS responsive characteristics ensure specific release of prodrugs in tumor cells with high level of ROS thereby reducing side effects on normal cells and tissues.The endogenous ROS and newly generated ROS by ART can reduce the expression of CDA and optimizes the metabolism of GEM,and the accumulated ROS can also induce apoptosis of tumor cells,realizing synergistic anti-tumor effect of chemical drugs and traditional Chinese medicines.This paper proposes a simple method by using clinically approved drugs to improve the insufficient effect of existing chemotherapy and overcome resistance,which has potential to appropriately shorten the drug development cycle and accelerate the clinical investigation of drugs.

MILP Optimization Model for Assessing the Participation of Distributed Residential PV-battery Systems in Ancillary Services Market

A novel non-linear stochastic method based on a Mixed-Integer Linear Programming(MILP)optimization model is proposed to optimally manage a high number of photovoltaic(PV)-battery systems for the provision of up and down regulation in the ancillary services market.This method,considers both the technical constraints of the power system,and those of the equipment used by all the prosumers.This allows an aggregator of many residential prosumers endowed with photovoltaic(PV)-battery systems to evaluate the baseline of the aggregate by minimizing the costs related to the electrical energy absorbed from the grid and then to assess the up and down flexibility curves with relative offer prices.As confirmed by simulation results carried out considering different realistic case studies,the method can effectively be used by an aggregator to evaluate the economic impact of its participation in the ancillary services market,both for the aggregator and for its prosumers.