Structure-based Discovery of Novel CK2α-Binding Cyclic Peptides with Anti-cancer Activity.

Protein kinase CK2 is considered as an emerging target in cancer therapy, and recent efforts have been made to develop its ATP-competitive inhibitors, but achieving selectivity with respect to related kinases remains challenging because of the highly conserved ATP-binding pocket of kinases. Non-ATP competitive inhibitors might solve this challenge; one such strategy is to identify compounds that target the CK2α/CK2β interface as CK2 holoenzyme antagonists. Here we improved the binding affinity to CK2α and cell-based anti-cancer activity of a CK2β-derived cyclic peptide (Pc) by combining structure-based computational design with experimental evaluation.

Rational Design of Coumarin Derivatives as CK2 Inhibitors by Improving the Interaction with the Hinge Region.

Design of novel coumarin derivatives as CK2 inhibitors were attempted by targeting the interaction with the hinge region. A set of substituents capable of forming a hydrogen bond or halogen bond with the hinge region were screened in silico, and trifluoromethyl emerges as a promising motif by forming favorable electrostatic interaction and a presumable halogen bond with the hinge region. As proof of concept, three trifluoromethyl derivatives of coumarin were synthesized and tested in vitro.

Experimental and Theoretical Investigation of Effects of Ethanol and Acetic Acid on Carcinogenic NDMA Formation in Simulated Gastric Fluid.

N-nitrosodimethylamine (NDMA), as a representative of endogenously formed N-nitroso compounds (NOCs), has become the focus of considerable research interest due to its unusually high carcinogenicity. In this study, effects of ethanol and acetic acid on the formation of NDMA from dimethylamine (DMA) and nitrite in simulated gastric fluid (SGF) were investigated. Experimental results showed that ethanol in the concentrations of 1-8% (v/v) and acetic acid in the concentrations of 0.

Iron(II) porphyrins induced conversion of nitrite into nitric oxide: A computational study.

Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed.

Infection and integration of high-risk human papillomavirus in HPV-associated cancer cells.

High-risk human papillomaviruses (HPV) have been associated with many human cancers in clinical studies. Integration of HPV into the human genome is a suspected etiological factor in the induction of some HPV-associated cancers. The characteristics of HPV integration in certain HPV-integrated cancer cells remain unclear.

Integrated HPV genomes tend to integrate in gene desert areas in the CaSki, HeLa, and SiHa cervical cancer cell lines.

Aims: The integration preferences of human papillomavirus (HPV) have been intensively studied and contested over recent years. To disclose the integration preferences of high-risk HPV in cervical cancer, HPV transcriptional sites and features in different cervical cancer cell lines were identified.

Main Methods: In this study, three cervical cancer cell lines (CaSki, HeLa, and SiHa) were subjected for HPV genome status determination by amplification of papillomavirus oncogene transcripts (APOT) assay.

Determination of lead, cadmium, copper, and nickel in the tonghui river of beijing, china, by cloud point extraction-high resolution continuum source graphite furnace atomic absorption spectrometry.

Heavy metal contamination of water has become an important problem in recent years. Most hazardous heavy metals exist in environmental water in trace or ultra-trace amounts, which requires establishing highly sensitive analytical methods. In this research, quantitative analyses were performed using high-resolution continuum source graphite furnace atomic absorption spectrometry combined with cloud point extraction (CPE) to determine Pb, Cd, Cu, and Ni levels in environmental surface water.

Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap.

Objective: Skin damage induced by ischemia/reperfusion (I/R) is a multifactorial process that often occurs in plastic surgery. The mechanisms of I/R injury include hypoxia, inflammation, and oxidative damage. Hydrogen gas has been reported to alleviate cerebral I/R injury by acting as a free radical scavenger.

[Comparison of prediction performance of PAHs carcinogenicity between a BALB/c-E6E7 cell transformation assay and a BALB/c 3T3 cell transformation assay].

Objective: To predict the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs) by cell transformation assay using BALB/c 3T3 cells and HPV16-E6E7-transfected BALB/c 3T3 cells (BALB/c-E6E7 cells).

Methods: The cell transformation assays induced by PAHs using BALB-E6E7 cells and BALB/c 3T3 cells.

Results: The initiating and promoting activities of PAHs examined in a BALB-E6E7 cell transformation assay were similar to in a BALB/c 3T3 cell transformation assay, which was up to the standard of agents classified by the IARC.

[Determination of trace lead in environmental water by cloud point extraction-high resolution continuum source graphite furnace atomic absorption spectrometry].

Comparison investigations were performed for the enrichment method of lead in environmental waters, including coprecipitation, ion exchange and cloud point extraction (CPE). CPE was selected as the optimal enrichment method because of its less consumption of water sample, higher enrichment factor and simpler procedure than the other enrichment methods. Pb contents in the water samples from Tonghui River in Beijing were determined by high resolution continuum source graphite furnace atomic absorption spectrometry coupled with CPE enrichment.

[Determination of Pb, Cd and Cr in food by high resolution continuum source graphite furnace atomic absorption spectrometry].

The contents of lead, cadmium and chromium were determined for 22 kinds of foods including cereals, vegetables, beverage, sea foods and dairy products by using high resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GFAAS). The methods for sample preparation, digestion, and quantitative analysis were established, by which satisfying analytical precision (RSD = 1.3%-4.

[Progress in study of biomolecular damages by Raman spectroscopy].

Raman spectroscopy is an analytical techniques based on Raman scattering, which gives information of molecular vibration and rotation. Raman spectroscopy has been widely employed in the investigations of the structure of biomolacules, because it has many advantages over the common chemical analysis. Raman spectroscopy is non-destructive to the samples.

[Rapid detection of 6-benzylaminopurine residues in sprout beans by surface-enhanced raman spectroscopy].

New method for rapid and quantitative analysis of 6-benzylaminopurine (6-BA) residues in sprout beans was studied by using FAST-SPE and portable surface-enhanced Raman spectroscopy (SERS). With homemade sprout bean samples as blank control, 6-BA solutions extracted from inserted-treatment samples showed typical characteristic Raman peaks at 1002 cm(-1) tested by SERS, and normalized 1002 cm(-1) intensities had a good linear relationship with gradient concentrations of 6-BA insert-standard solutions. The high concentration linear range was 0.

Reactions of amine and peroxynitrite: evidence for hydroxylation as predominant reaction and new insight into the modulation of CO2.

Peroxynitrite is related to numerous diseases including cardiovascular diseases, inflammation, and cancer. In order to expand the understanding for the toxicology of peroxynitrite in biological system, the reactions of amine (morpholine as a probe) with peroxynitrite and the modulation of CO2 were investigated by using DFT methods. The results strongly indicate that the hydroxylation of amine by peroxynitrous acid ONOOH, which was previously overlooked by most studies, is predominant relative to the widely reported nitration and nitrosation in the absence of CO2.

[Determination of aluminum in wheat flour food by microwave digestion-high resolution continuum source graphite furnace atomic absorption spectrometry].

The contents of aluminum (Al) in four kinds of wheat flour food (noodle, dumpling wrapper, twisted cruller and soda biscuit) were determined by high resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GFAAS) combined with microwave digestion. The samples were completely digested by the mixture of HNO3 and H2O2 in closed polytetrafluoroethylene (PTFE) vessels. The conditions for microwave digestion, pyrolysis temperature and atomization temperature were optimized.

[Progress in study of biomacromolecular damages by infrared spectroscopy].

Infrared spectroscopy (IR) is employed as an important tool in the investigation of biological macromolecules because of its high sensitivity and nondestructivity to samples. When proteins, lipids or nucleic acids are damaged, the position, shape and intensity of their IR characteristic absorption peaks will be significantly changed. This provides evidences for the determination of the damages of biomolecules, which further shed light on the clarification of the occurrence, development and early prevention of some diseases.

Carbon dioxide in the nitrosation of amine: catalyst or inhibitor?

Nitrosamines are a class of carcinogenic, mutagenic, and teratogenic compounds generally produced from the nitrosation of amine. This paper investigates the mechanism for the formation of nitrosodimethylamine (NDMA) from the nitrosation of dimethylamine (DMA) by four common nitrosating agents (NO(2)(-), ONOO(-), N(2)O(3), and ONCl) in the absence and presence of CO(2) using the DFT method. New insights are provided into the mechanism, emphasizing that the interactions of CO(2) with amine and nitrosating agents are both potentially important in influencing the role of CO(2) (catalyst or inhibitor).

[Pretreatment methods of urine proteomics in children with primary nephrotic syndrome].

Objective: To optimize a pretreatment method of urine proteomics in children with primary nephrotic syndrome.

Methods: Urine from children with primary nephrotic syndrome was treated in different pH and isolated by cold acetone precipitation for different durations. Then the amounts and kinds of proteins were compared by quantify, SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional electrophoresis (2-DE) in order to optimize a way to deal with urine protein.

[Experimental research on anti-respiratory syncytial virus effect in vitro of earthworm coelomic fluid].

Objective: To explore the antivirus function in vitro of earthworm coelomic fluid (ECF) by researching its effect on inhibiting respiratory syncytial virus (RSV).

Methods: By the method of Hep-2 cell culture and using ribavirin as a positive control, the anti-RSV effect of ECF was investigated by observing cytopathic effect (CPE) with MTT colorimetric assay.

Results: In Hep-2 cells, the CC50 of ECF and ribavirin were 3.

Convenient ultrasound-mediated synthesis of 1,4-diazabutadienes under solvent-free conditions.

An ultrasound-assisted preparation of 1,4-diazabutadienes via smooth condensation of diketones with amines under solvent-free conditions is described. The generality of this method was examined by the synthesized N,N'-diaryl- and N,N'-dialkyl-1,4-diazabutadiene derivatives. In addition to experimental simplicity, the main advantages of the procedure are mild conditions, short reaction time (2-15 min) and high yields (71-98%).

Preparation of 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid catalyzed by iron(III)porphyrins with (diacetoxyiodo)benzene.

Using iron(III)porphyrins in combination with (diacetoxyiodo)benzene allows for the conversion of 2,9-bis(bromomethyl)-4,7-diphenyl-1,10-phenanthroline into 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid. This method provides a cost-effective and environmentally-friendly oxidation procedure using less toxic PhI(OAc)2 and biologically relevant iron(III)porphyrins. The catalytic activity of five kinds of iron-metallated functional porphyrins were investigated using different oxidants, including air, H2O2, PhI(OAc)2, PhIO and NaClO.

Anodic oxidation of catechols in the presence of alpha-oxoketene N,N-acetals with a tetrahydropyrimidine ring: selective alpha-arylation reaction.

The electrochemical oxidation of catechols leads to the formation of o-benzoquinones. This property has been applied to effectively synthesize alpha-arylated products of alpha-oxoketene N,N-acetals with a tetrahydropyrimidine ring.

[An improved BALB/c 3T3 cell transformation assay and its application in the cocarcinogenesis study].

Objective: To improve the protocol of BALB/c 3T3 cell transformation assay, and apply it to the cocarcinogenesis study.

Method: Appropriate serum concentration, culture media and method of administration were selected by testing their effects on the growth and transformation of BALB/c 3T3 cells. The co-carcinogenic activity between diethylnitrosamine (DEN) and microcystin-LR (MC-LR) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined using the improved cell transformation assay.