[The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells].

OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP+ cells was tested by colony-forming units assays (CFU). The cytotoxic effect was further detected by transplant assays ex vivo. Telomerase activity assay, C-circle assay were used to measure the effects of compound on the length mechanism of telomere, RT-PCR was used to detected the changes of telomere. RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP+ cells significantly, slightly arrests the cell cycle at G0/G1 phase, and significantly inhibits colony formation and prolong the progression in MLL-AF9 leukemia mice model. The expression showed that the compound could slow the disease progression in MLL-AF9 leukemia mice significantly. Mechanistically, Nilo 22 could reduce the length of telomere by inhibiting telomerase activity and alternative lengthening of telomere (ALT). CONCLUSION: Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.

Peperomin E Induces Promoter Hypomethylation of Metastatic-Suppressor Genes and Attenuates Metastasis in Poorly Differentiated Gastric Cancer.

BACKGROUND/AIMS: Peperomin E (PepE), a natural secolignan isolated from the whole plant of Peperomia dindygulensis, has been reported by ourselves and others to display potent anti-cancer effects in many types cancer cells, especially gastric cancer. However, the effects of PepE on the metastasis of poorly-differentiated gastric cancer cells and the underlying molecular mechanisms have not been well elucidated. METHODS: We evaluated PepE effects on gastric cancer cell invasion and migration in vitro via wound healing and transwell assays and those on growth and metastasis in vivo using an orthotopic xenograft NOD-SCID mouse model. DNA methyltransferase (DNMT) activity was determined using a colorimetric DNMT activity/inhibition assay kit. PepE binding kinetics to DNMTs were determined using the bio-layer interferometry binding assay. Gene and protein levels of DNMTs, AMPKα-Sp1 signaling molecules, and metastatic-suppressor genes in PepE-treated gastric cancer cells were determined using quantitative reverse transcription-PCR arrays and western blotting. The effect of PepE on Sp1 binding to the DNMT promoter was determined by electrophoretic mobility-shift assay. Global DNA methylation levels were determined using liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The methylation status of silenced metastatic-suppressor genes (MSGs) in gastric cancer cells was investigated by methylation-specific PCR. RESULTS: PepE can dose-dependently suppress invasion and migration of poorly-differentiated gastric cancer cells in vitro and in vivo with low toxicity against normal cells. Mechanistically, PepE not only covalently binds to the catalytic domain of DNMT1 and inhibits its activity (IC50 value 3.61 µM) but also down-regulates DNMT1, 3a, and 3b mRNA and protein expression in in gastric cancer cells, by disruption of the physical interaction of Sp1 with the DNMT1, 3a, and 3b promoter and mediation of the AMPKα-Sp1 signaling pathway. The dual inhibition activity of PepE toward DNMTs renders a relative global DNA hypomethylation, which induces MSG promoter hypomethylation (e.g., E-cadherin and TIMP3) and enhances their expression in gastric cancer cells. CONCLUSION: Collectively, our data indicated that PepE may represent a promising therapeutic lead compound for intervention in gastric cancer metastasis and may also exhibit potential as a DNA methylation inhibitor for use in epigenetic cancer therapy.

Doping-Enhanced Short-Range Order of Perovskite Nanocrystals for Near-Unity Violet Luminescence Quantum Yield.

All-inorganic perovskite nanocrystals (NCs) have emerged as a new generation of low-cost semiconducting luminescent system for optoelectronic applications. The room-temperature photoluminescence quantum yields (PLQYs) of these NCs in the green and red spectral range approach unity. However, their PLQYs in the violet are much lower, and an insightful understanding of such poor performance remains missing. We report a general strategy for the synthesis of all-inorganic violet-emitting perovskite NCs with near-unity PLQYs through engineering local order of the lattice by nickel ion doping. A broad range of experimental characterizations, including steady-state and time-resolved luminescence spectroscopy, X-ray absorption spectra, and magic angle spinning nuclear magnetic resonance spectra, reveal that the low PLQY in undoped NCs is associated with short-range disorder of the lattice induced by intrinsic defects such as halide vacancies and that Ni doping can substantially eliminate these defects and result in increased short-range order of the lattice. Density functional theory calculations reveal that Ni doping of perovskites causes an increase of defect formation energy and does not introduce deep trap states in the band gap, which is suggested to be the main reason for the improved local structural order and near-unity PLQY. Our ability to obtain violet-emitting perovskite NCs with near-perfect properties opens the door for a range of applications in violet-emitting perovskite-based devices such as light-emitting diodes, single-photon sources, lasers, and beyond.

Ion-Exchangeable Microporous Polyoxometalate Compounds with Off-Center Dopants Exhibiting Unconventional Luminescence.

The synthesis of luminescent polyoxometalates (POMs) typically relies on the assembly of POM ligands with rare earth or transition metals, placing significant constraints on the composition, structure, and hence the luminescence properties of the resultant systems. Herein, we show that the ion-exchange strategy can be used for the synthesis of novel POM-based luminescent materials. We demonstrate that introducing bismuth ions into an ion-exchangeable, microporous POM compound yields an unconventional system luminescing in the near-infrared region. Experimental characterization, coupled with quantum chemical calculations, confirms that bismuth ions site-specifically occupy an off-center site in the lattice, and have an asymmetric coordination geometry unattainable by other means, thus giving rise to peculiar emission. Our findings offer an effective strategy for the synthesis of POM-based luminescent materials, and the design concept may potentially be adapted to the creation of POM-based systems with other functionalities.

Evaluation of magnetic particles modified with a hydrophobic charge-induction ligand for antibody capture.

Magnetic particles modified with 5-amino-benzimidazole (ABI), a ligand for hydrophobic charge-induction chromatography, were prepared and used for antibody capture. In this study, with IgG as the model target, and bovine serum albumin (BSA) as the model impurity, the separation mechanism and process of IgG was investigated. The adsorption isotherms of IgG and BSA were measured, and the effects of pH were investigated in the range of pH 4.0-8.0. The maximum adsorption capacity of IgG on the particles was 180mg/ml at pH 7.0, while low adsorption capacity of BSA (64mg/ml) was found at pH 7.0, resulting in good selectivity. The protein-ligand interactions were elucidated by adding NaCl and glycerol. The results indicated the hydrophobic interactions were the main forces for IgG-ligand association. Moreover, the batch uptake and desorption experiments demonstrated the fast adsorption and desorption processes for IgG separation. The purity of IgG separated from mimetic serum could reach 98.6%, and the purity of monoclonal antibody (mAb) from a cell culture supernatant was 97.1%. Magnetic particles with hydrophobic charge-induction ligands showed a robust performance and could purify antibody directly from the complicated feedstock without clarification, which would improve the efficiency of antibody purification.

Measurement of dissolved reactive phosphorus in water with polyquaternary ammonium salt as a binding agent in diffusive gradients in thin-films technique.

Diffusive gradients in thin-films (DGT) sampler with a polyquaternary ammonium salt (PQAS) aqueous solution as a binding phase and a dialysis membrane as a diffusive phase (PQAS DGT) was developed for the measurement of dissolved reactive phosphorus (DRP) in water. The performance of PQAS DGT was not dependent upon pH 3-10 and ionic strength from 1 × 10(-4) to 1 mol L(-1). The effective binding capacity of PQAS DGT containing 2.0 mL of 0.050 mol L(-1) PQAS solution was estimated as 9.9 µg cm(-2). The measurement of DRP in a synthetic solution by PQAS DGT over a 48 h deployment period demonstrated high consistency with the concentration of DRP in the synthetic solution measured directly by the ammonium molybdate spectrophotometric method. Field deployments of PQAS DGT samplers allowed for accurate measurement of the DRP concentration in situ. The advantages of PQAS DGT include no requirement of the elution steps and direct concentration measurements of the binding phase.

Selective sampling and measurement of Cr (VI) in water with polyquaternary ammonium salt as a binding agent in diffusive gradients in thin-films technique.

A diffusive gradients in thin films (DGT) device with polyquaternary ammonium salt (PQAS) as a novel binding agent (PQAS DGT) combined with graphite furnace atomic absorption spectrometry (GFAAS) was developed for the selective sampling and measurement of Cr (VI) in water. The performance of PQAS DGT was independent of pH 3-12 and ionic strength from 1 × 10(-3) to 1 molL(-1). DGT validation experiments showed that Cr (VI) was measured accurately as well as selectively by PQAS DGT, whereas Cr (III) was not determined quantitatively. Compared with diphenylcarbazide spectrophotometric method (DPC), the measurement of Cr (VI) with PQAS DGT was agreement with that of DPC method in the industrial wastewater. PQAS-DGT device had been successfully deployed in local freshwater. The concentrations of Cr (VI) determined by PQAS DGT coupled with GFAAS in Nuer River, Ling River and North Lake were 0.73 ± 0.09 µg L(-1), 0.50 ± 0.07 µg L(-1) and 0.61 ± 0.07 µg L(-1), respectively. The results indicate that PQAS DGT device can be used for the selective sampling and measurement Cr (VI) in water and its detection limit is lower than that of DPC method.

[Epidemiological survey of asthma in children aged 0-14 years in the Futian District of Shenzhen, China between 2010 and 2011].

OBJECTIVE: To investigate the prevalence rate and risk factors for asthma in children from the Futian District of Shenzhen, China who were aged from 0-14 years between 2010 and 2011, and to provide scientific evidence for the prevention and treatment of childhood asthma. METHODS: A multistage stratified cluster sampling survey of 7168 children aged 0-14 years from the Futian District of Shenzhen was conducted using the Third National Childhood Asthma Epidemiological Questionnaire 2010, to investigate the prevalence rate of childhood asthma. A case-control study (1∶1) and logistic regression analysis were used to investigate the risk factors for childhood asthma. RESULTS: Of the 7168 children surveyed, 169 were diagnosed with asthma, with a total prevalence rate of 2.36%. The prevalence rate was higher in males than in females (3.06% vs 1.55%, P<0.01). Of the 169 cases, 115 (68.1%) had their first asthma attack before the age of 3 years, 95 (56.2%) had moderate attacks, 159 (94.1%) had sudden attacks, 86 (50.9%) suffered from asthma during periods of seasonal change, 97 (57.4%) had attacks before going to bed, 157 (92.9%) suffered from asthma caused by respiratory infection, and 159 (94.1%) had sneezing as the sign of oncoming attack. The case-control study (including the 169 asthma cases and 169 healthy children) and logistic regression analysis both showed that the independent risk factors for asthma in children were a personal history of drug allergy (OR=3.431, 95%CI: 1.240-9.496, P=0.018), a history of food allergy (OR=4.043, 95%CI: 1.669-9.795, P= 0.002), allergic rhinitis (OR=9.686, 95%CI: 5.137-18.263, P<0.001), and a family history of allergy (OR=4.059, 95%CI: 2.054-8.018, P<0.001). CONCLUSIONS: The prevalence rate of asthma was 2.36% in children aged 0-14 years in the Futian District of Shenzhen between 2010 and 2011. The prevalence rate had not increased when compared with the rate in this region 10 years earlier (2.39%). The prevalence rate of childhood asthma is higher in males than in females. Personal history of drug allergy, food allergy, allergic rhinitis and a family history of allergy are the independent risk factors for childhood asthma in this region.

[The interactions between the circadian clock and aging].

It is well known that almost all organisms ranging from single cell creatures to human beings exhibit circadian rhythms in physiology and behavior under the control of the internal circadian clock. The internal circadian clock is composed of a master clock which is localized in the suprachiasmatic nucleus and the peripheral clocks located in peripheral tissues such as the liver and heart. Along with aging, the circadian rhythm alters in many aspects, including the amplitude, free-running period and the expression phase. On the other hand, the circadian clock also influences the process of aging. The disorganized circadian rhythm accelerates the aging process. This article briefly reviews the recent progress in the interactions between the circadian clock and aging, and provides evidence to further understand the mechanism of aging and the impact of aging on the organisms.

[Separation and determination of selenium polysaccharide in enriched-Se cordyceps militaris].

In the present paper, the water soluble selenium polysaccharide was extracted, and isolated and purified preliminarily. The traditional method was used to extract selenium polysaccharide, which was extracted by water and sank by ethanol. The work also focused on the determination of the experiment conditions, optimizing the experiment conditions such as proportion of extract solution, extract temperature, extract times, proportion of ethanol, and standing time. The recovery of selenium polysaccharide under these conditions is 5.76%. Polysaccharide content in the powder is 46.6%, and selenium content is 92.3 mg x kg(-1).