Cancer cells undergoing epigenetic transition show short-term resistance and are transformed into cells with medium-term resistance by drug treatment

To elucidate the epigenetic mechanisms of drug resistance, epigenetically reprogrammed H460 cancer cells (R-H460) were established by the transient introduction of reprogramming factors. Then, the R-H460 cells were induced to differentiate by the withdrawal of stem cell media for various durations, which resulted in differentiated R-H460 cells (dR-H460). Notably, dR-H460 cells differentiated for 13 days (13dR-H460 cells) formed a significantly greater number of colonies showing drug resistance to both cisplatin and paclitaxel, whereas the dR-H460 cells differentiated for 40 days (40dR-H460 cells) lost drug resistance; this suggests that 13dR-cancer cells present short-term resistance (less than a month). Similarly, increased drug resistance to both cisplatin and paclitaxel was observed in another R-cancer cell model prepared from N87 cells. The resistant phenotype of the cisplatin-resistant (CR) colonies obtained through cisplatin treatment was maintained for 2–3 months after drug treatment, suggesting that drug treatment transforms cells with short-term resistance into cells with medium-term resistance. In single-cell analyses, heterogeneity was not found to increase in 13dR-H460 cells, suggesting that cancer cells with short-term resistance, rather than heterogeneous cells, may confer epigenetically driven drug resistance in our reprogrammed cancer model. The epigenetically driven short-term and medium-term drug resistance mechanisms could provide new cancer-fighting strategies involving the control of cancer cells during epigenetic transition.Subject terms: Tumour heterogeneity, Epigenetics     

富氧条件下乙炔选择催化还原NOx

Acetylene as a reducing agent of metal exchanged HY catalysts, for selective catalytic reduction of NO in the reaction system of 0.16% NO, 0 （C2H2-SCR） was investigated over a series 08% C2H2, and 9.95% O2 （volume percent） in He. 75% of NO conversion to N2 with hydrocarbon efficiency about 1.5 was achieved over a Ce-HY catalyst around 300 ℃. The NO removal level was comparable with that of selective catalytic reduction of NOx by C3H6 reported in literatures, although only one third of the reducing agent in carbon moles was used in the C2H2-SCR of NO. The protons in zeolite were crucial to the C2H2-SCR of NO, and the performance of HY in the reaction was significantly promoted by cerium incorporation into the zeolite. NO2 was proposed to be the intermediate of NO reduction to N2, and the oxidation of NO to NO2 was rate-determining step of the C2H2-SCR of NO over Ce-HY. The suggestion was well supported by the results of the NO oxidation with O2, and the C2H2 consumption under the conditions in the presence or absence of NO.     

New Stephaoxocane Alkaloids from Stephania longa

Three new stephaoxocane‐type alkaloids, stephalonganines A–C ( 1 – 3 ), together with the known eletefine ( 4 ), were isolated from the whole plant of Stephania longa. Their structures were fully characterized spectroscopically, and the absolute configurations of the new alkaloids were assigned by comparison of their circular‐dichroism (CD) data with those of 1,2‐dihydrostephaoxocanine ( 5 ), in combination with 2D‐NMR experiments.     

Selective Recognition of Calcium Ion through Liquid Membrane

The mole transport rate of alkaline earth metal ions through a bulk liquid membrane and a supported liquid membrane using a series of proton diionizable acyclic polyethers was measured. Among alkaline earth metal ions, the calcium ion was observed to be selectively transported in both single and competitive transport experiments. Potentiometric titration and solution calorimetric titration also gave calcium selectivity over other alkaline earth metal ions. Acyclic polyether bearing a diethylene glycol unit andn-tetradecyl lipophilic chain at the α position of carboxylic acid affords the best selectivity for the calcium ion in bulk and supported liquid membranes.     

Lipid-protein interactions in the membrane: studies with model peptides

We have used fluorescence quenching of tryptophan-containing trans-membrane peptides by bromine-containing phospholipids to study the specificity of peptide-lipid interactions. We have synthesized peptides Ac-K2GLm WLnK2A-amide where m = 7 and n = 9 (L16) and m = 10 and n = 12 (L22). Binding constants of L22 for dioleoylphosphatidylserine [di(C18 : 1)PS] or dioleoylphosphatidic acid [di(C18 : 1)PA] relative to dieoleoylphosphatidylcholine [di(C18 : 1)PC] were close to 1. However, for L16, whilst the bulk of the di(C18 : 1)PA molecules bound with a binding constant relative to di(C18 : 1)PC close to 1, a small number of di(C18 : 1)PA molecules bound much more strongly. Assuming just one high affinity binding site on L16 for anionic lipid, the affinity of the site for di(C18 : 1)PS was calculated to be ca. 8 times that for di (C18 : 1)PC. The relative binding constant was little affected by ionic strength and close contact between the anionic headgroup of di(C18 : 1)PS and a lysine residue on the peptide was suggested. The relative binding constant for di(C18 : 1)PS at this high affinity site was less than for di(C18 : 1)PA. Cholesterol interacts with L22 with an affinity about 0.7 of that of di(C18 : 1)PC. The structure of the peptide itself is important. The peptide Ac-KKGYL6WL8YKKA-amide (Y2L14) incorporated into bilayers of dinervonylphosphatidylcholine [di(C24 : 1)PC] whereas L16 did not incorporate into this lipid. It is suggested that thinning of a lipid bilayer around a peptide to give optimal hydrophobic matching is less energetically unfavourable when a Tyr residue is located in the lipid/water interfacial region.     

Azido- or hydroxyl-capped half-cubanes containing Cp*Rh fragments: [Cp*3Rh3(mu-X)3(mu3-X)]2+ (X-=OH- or N3-)

Treatment of [Cp*Rh(H(2)O)(3)](OTf)(2) (1) with Me(3)SiNH-t-Bu in acetone gave a hydroxyl-capped half-cubane [Cp*(3)Rh(3)(mu-OH)(3)(mu(3)-OH)](OTf)(3)(t-BuNH(3)) (2). Slow diffusion of Me(3)SiN(3) in diethyl ether into compound in acetone produced an azido-capped half-cubane [Cp*(3)Rh(3)(mu-N(3))(3)(mu(3)-N(3))](OTf)(2) (3). On the other hand, treating 1 with Me(3)SiN(3) in acetone gave an azido-bridged, dinuclear rhodium(III) complex [Cp*Rh(mu-N(3))(OH(2))](2)(OTf)(2) (4). Complexes 2 and 3 represent the first azido- or hydroxyl-capped, incomplete cubane-type Rh clusters. Under appropriate conditions, complexes 2 and 3 could be converted to complex 4. The structures of all products were determined by X-ray diffraction.     

The Effect of Vibrational Excitation of Molecules on Plasmachemical Reactions Involving Methane and Nitrogen

An experimental study of plasmachemical reaction involving CH₄ and N₂ molecules in rf discharge was studied in order to know the effect of vibrational excitation of N₂ molecules. When the relative nitrogen concentration was greater than 0.8, the main product of CH₄ decomposition was HCN, and the rate of methane decomposition at this condition was faster than that one in pure methane. These results could be confirmed through the mass spectroscopic method. The reason for these results is the vibrational energy of N₂ excited by rf discharge. The chain reaction mechanisms of producing HCN by vibrational excitation of N₂ were examined closely through numerical simulation. The rate-controlling step was the dissociation reaction of excited nitrogen molecule to the atomic nitrogen, so the process of HCN synthesis was limited by the value of reaction constant, k^N.     

Direct determination of estriol 3- and 16-glucuronides in pregnancy urine by column-switching liquid chromatography with electrospray tandem mass spectrometry

Using column-switching liquid chromatography/tandem mass spectrometry (LC-MS/MS), we developed an improved analytical method of urinary estriol glucuronides. This new method is derived predominantly from maternal and fetal precursors in pregnancy. We used in the following procedure: first, we filtered urine samples with a membrane filter. Next, we directly injected the 50 microL aliquot of urine samples onto a pre-column. Then, after activating the column-switching valve, we backflushed the loaded samples onto the C(18) analytical column. Urine samples can be assayed within 20 min without any sample preparation steps. We monitored separated estriol glucuronides by negative electrospray ionization (ESI) and selected-reaction monitoring (SRM). The calibration range of estriol-3-glucuronide (E3-3G) and estriol-16-glucuronide (E3-16G) was 0.1-20 microg/mL and the linearity of the method was 0.9984 for E3-3G and 0.9987 for E3-16G. The limits of detection at a signal-to-noise (S/N) ratio of 3 were 10 ng/mL (E3-3G) and 5 ng/mL (E3-16G). The analytical recovery was over 85% and, in general, inter-day and intra-day variability for precision and accuracy were less than 10%. When applied to a pregnancy urine sample to biomedical monitoring of the function of the maternal/fetal unit, the proposed method allowed rapid and sensitive screening for the detection of E3-3G and E3-16G.     

Reversed-phase liquid chromatographic method for the analysis of aminoglycoside antibiotics using pre-column derivatization with phenylisocyanate

A pre-column derivatization liquid chromatographic method has been developed for the analysis of aminoglycoside antibiotics using phenylisocyanate as a derivatization reagent. Derivatives including kanamycin, neomycin and gentamicin were formed by reaction of the analytes with phenylisocyanate in the presence of triethylamine. Phenylisocyanato groups were attached to corresponding amino groups of aminoglycoside and their molecular mass was confirmed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The experimental conditions for derivatization and separation of aminoglycoside derivatives were optimized and validated. A simple liquid chromatographic method for the determination of aminoglycoside antibiotics was demonstrated.     

A facile electrochemical synthesis of caffeic acid derivatives in the presence of acetylacetone or methyl acetoacetate in aqueous medium

The anodic oxidation of caffeic acid in the presence of acetylacetone or methyl acetoacetate in aqueous solution has been studied by cyclic voltammetry and controlled-potential electrolysis techniques. The result showed that caffeic acid was oxidized to the corresponding o-benzoquinone, which underwent further Michael-addition with acetylacetone or methyl acetoacetate to produce caffeic acid derivative 3,4-dihydroxy-6-(1-acetylacetone)-yl cinnamic acid 4a or 3,4-dihydroxy-6-(1-acetyl-methylacetate)-yl cinnamic acid 4b.