Zhiguo Zheng

The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer.

Primary and acquired drug resistance is one of the main obstacles encountered in high-grade serous ovarian cancer (HGSC) chemotherapy. Cisplatin induces DNA damage through cross-linking and long integrated non-coding RNAs (lincRNAs) play an important role in chemical induced DNA-damage response, which suggests that lincRNAs may be also associated with cisplatin resistance. However, the mechanism of long integrated non-coding RNAs (lincRNAs) acting on cisplatin resistance is not well understood. Here, we showed that expression of lin-RECK-3, H19, LUCAT1, LINC00961, and linc-CARS2-2 was enhanced in cisplatin-resistant A2780-DR cells, while transcriptome sequencing showed decreased Linc-TNFRSF19-1 and LINC00515 expression. Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19-knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance.

Corrigendum: Lysine Acetylation and Succinylation in HeLa Cells and their Essential Roles in Response to UV-induced Stress

This corrects the article DOI: 10.1038/srep30212.

Curcumol Promotes Vascular Endothelial Growth Factor (VEGF)-Mediated Diabetic Wound Healing in Streptozotocin-Induced Hyperglycemic Rats

Background Wound healing in chronic diabetic mellitus is mainly associated with the management of angiogenesis. The angiogenic mechanism of vascular endothelial growth factor (VEGF) has been widely studied in the context of diabetic ulcers. The aim of this study was to investigate the wound-healing potential of curcumol in streptozotocin-induced diabetic rats. Material/Methods Sixty male SD (Sprague Dawley) rats were purchased and randomly assigned into four groups: a control group and a model group treated with blank ointment, a high-dose curcumol group, and a low-dose curcumol group. The number of animals in each group was 15. Diabetes was induced by an intraperitoneal injection of streptozotocin. Two cutaneous wounds were incised at the dorsal region of all the experimental animals. Wound healing was assessed for all animal groups by observing the rate of wound closure. The expression of VEGF at the wound sites was studied by immunohistochemical staining to evaluate the vascular endothelial cell reaction. VEGF protein and related mRNA levels were analyzed by Western blotting and RT-PCR (reverse transcription-polymerase chain reaction). Results Curcumol treatment significantly increased the rates of wound closure in treated animals, and hence wound healing was drastically enhanced for treatment groups compared to control groups. Histological observations and related mRNA and protein levels showed a higher VEGF expression in the treatment groups. Conclusions Our analyses clearly suggested that the observed enhancement in wound healing as a result of curcumol administration was attributable to VEGF-mediated angiogenesis.

Extracellular Proteome Changes of Deinococcus radiodurans Under γ-Irradiation Stress Conditions

To analysis the change of Deinococcus radiodurans extracellular proteins recovering from γ-irradiation, we examined extracellular proteome changes using two-dimensional polyacrylamide gel electrophoresis. Twenty-six spots on the gel of irradiated sample were showed significant changes compared with spots on the control gel. Using peptide mass fingerprinting via matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), 21 different proteins could be distinguished. Among the identified proteins, seven are classified in transport and metabolism, and one is involved in intracellular trafficking and secretion. The other proteins are known to several functions in the cytosol. Most of the proteins have not previously been reported to be relevant to radioresistance. These results imply that the transmembrane transportation is involved in and contributes to the radioresistance in this organism.

Thin film polarization colour-selective beamsplitter

Abstract A thin film polarization-selective beamsplitter system used for a liquid-crystal light-valve image projector has been presented. The system involves three beamsplitters which serve as either a polarizer/analyzer or a separator/synthesizer for the three primary colours. These filters have been realized with multilayer optical coatings. The design, manufacture and performance measurement of the filters have been described.

Overexpression of SMARCA2 or CAMK2D is associated with cisplatin resistance in human epithelial ovarian cancer

Ovarian cancer is one of the most lethal types of gynecological cancer. Drug resistance is a major underlying cause of treatment failure, which has lead to continued poor mortality and morbidity rates in patients. In the present study, highly sensitive transcriptome sequencing was performed to systematically identify differentially expressed mRNAs in cisplatin-sensitive (A2780) and -resistant (A2780-DR) cells. Calcium/calmodulin dependent protein kinase IIδ (CAMK2D) and SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily A member 2 (SMARCA2) were identified as exhibiting increased expression in cisplatin-resistant cells. Overexpression of either SMARCA2 or CAMK2D led to a significant increase in the survival rates of A2780 and SKVO3 cells following cisplatin treatment. To further verify the contribution of these two genes in the development of drug resistance, the RNA levels in tissues with different recurrence-free survival (RFS) rates were compared. An increased mRNA level of CAMK2D was detected in samples with shorter RFS rates. An apoptosis assay revealed that overexpression of SMARCA2 or CAMK2D increased the resistance of ovarian cancer cells to cisplatin, as indicated by the decreased apoptotic cell populations. The levels of these two genes also affected the cell cycle and apoptosis-associated protein expression. Quantitative proteomic analyses revealed that overexpression of SMARCA2 or CAMK2D influences multiple metabolism and cancer-associated signaling pathways, which are critical for responses to cisplatin treatment and drug resistance development.