Implication of intracellular ROS formation, caspase-3 activation and Egr-1 induction in platycodon D-induced apoptosis of U937 human leukemia cells

Shin, D.Y.,Kim, G.Y.,Li, W.,Choi, B.T.,Kim, N.D.,Kang, H.S.,Choi, Y.H. Masson Pub. USA, Inc 2009 BIOMEDICINE AND PHARMACOTHERAPY Vol.63 No.2

Platycodon D is a major constituent of triterpene saponins found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. The results of previous studies have shown that this compound has in vitro growth-inhibitory activity in human cancer cells, however, the mechanism by which this action occurs is poorly understood. In this study, we examined the effects of platycodon D on the production of reactive oxygen species (ROS) and evaluated the association of these effects with apoptotic tumor cell death using a human leukemic U937 cell line. The results of this study demonstrate that platycodon D mediates ROS production, and that this mediation is followed by a decrease in mitochondrial membrane potential (MMP, ΔΨ<SUB>m</SUB>), activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Both the cytotoxic effects and apoptotic characteristics induced by platycodon D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 plays in the observed cytotoxic effect. Additionally, the transcription factor early growth response-1 (Egr-1) gene was transcriptionally activated and the levels of non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) protein were elevated in platycodon D-treated U937 cells. However, the quenching of ROS generation in response to treatment with a ROS scavenger, N-acetyl-l-cysteine, reversed the platycodon D-induced apoptosis effects via inhibition of Egr-1 activation, ROS production, MMP collapse, and the subsequent activation of caspase-3. Although further studies are needed to demonstrate that increased expression of Egr-1 by platycodon D leads directly to NAG-1 induction and subsequent apoptosis, our observations clearly indicate that ROS induced through Egr-1 activation are involved in the early molecular events involved in the platycodon D-induced apoptotic pathway.

Odorous VOC emission following land application of swine manure slurry

Parker, D.B.,Gilley, J.,Woodbury, B.,Kim, K.H.,Galvin, G.,Bartelt-Hunt, S.L.,Li, X.,Snow, D.D. Pergamon Press ; Elsevier [distribution] 2013 Atmospheric environment Vol.66 No.-

Swine manure is often applied to crop land as a fertilizer source. Odor emissions from land-applied swine manure may pose a nuisance to downwind populations if manure is not applied with sufficient forethought. A research project was conducted to assess the time decay of odorous volatile organic compound (VOC) emissions following land application of swine manure. Three land application methods were compared: surface application, incorporation 24 h after surface application, and injection. Emission rates were measured in field plots using a small wind tunnel and sorbent tubes. VOCs including eight volatile fatty acids, five aromatics, and two sulfur-containing compounds were quantified by gas chromatography-mass spectrometry. In most cases, a first order exponential decay model adequately described the flux versus time relationship for the 24 h period following land application, but the model sometimes overestimated flux in the 6-24 h range. The same model but with the time term squared adequately predicted flux over the entire 24 h period. Three compounds (4-methylphenol, skatole, and 4-ethylphenol) accounted for 93 percent of the summed odor activity value. First order decay constants (k) for these three compounds ranged from 0.157 to 0.996 h<SUP>-1</SUP>. When compared to surface application, injection of swine manure resulted in 80-95 percent lower flux for the most odorous aromatic compounds. These results show that VOC flux decreases rapidly following land application of swine manure, declining below levels of detection and near background levels after 4 to 8 h.

PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer

Lee, K-H,Park, J-W,Sung, H-S,Choi, Y-J,Kim, W H,Lee, H S,Chung, H-J,Shin, H-W,Cho, C-H,Kim, T-Y,Li, S-H,Youn, H-D,Kim, S J,Chun, Y-S Macmillan Publishers Limited 2015 Oncogene Vol.34 No.22

Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.

Fabrication of a three-dimensional bone marrow niche-like acute myeloid Leukemia disease model by an automated and controlled process using a robotic multicellular bioprinting system

Dana M. Alhattab,Ioannis Isaioglou,Salwa Alshehri,Zainab N. Khan,Hepi H. Susapto,Yanyan Li,Yara Marghani,Arwa A. Alghuneim,Rubén Díaz-Rúa,Sherin Abdelrahman,Shuroug AL-Bihani,Farid Ahmed,Raed I. Felim 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Acute myeloid leukemia (AML) is a hematological malignancy that remains a therapeutic challenge due to the high incidence of disease relapse. To better understand resistance mechanisms and identify novel therapies, robust preclinical models mimicking the bone marrow (BM) microenvironment are needed. This study aimed to achieve an automated fabrication process of a three-dimensional (3D) AML disease model that recapitulates the 3D spatial structure of the BM microenvironment and applies to drug screening and investigational studies. Methods To build this model, we investigated a unique class of tetramer peptides with an innate ability to selfassemble into stable hydrogel. An automated robotic bioprinting process was established to fabricate a 3D BM (niche-like) multicellular AML disease model comprised of leukemia cells and the BM’s stromal and endothelial cellular fractions. In addition, monoculture and dual-culture models were also fabricated. Leukemia cell compatibility, functionalities (in vitro and in vivo), and drug assessment studies using our model were performed. In addition, RNAseq and gene expression analysis using TaqMan arrays were also performed on 3D cultured stromal cells and primary leukemia cells. Results The selected peptide hydrogel formed a highly porous network of nanofibers with mechanical properties similar to the BM extracellular matrix. The robotic bioprinter and the novel quadruple coaxial nozzle enabled the automated fabrication of a 3D BM niche-like AML disease model with controlled deposition of multiple cell types into the model. This model supported the viability and growth of primary leukemic, endothelial, and stromal cells and recapitulated cell-cell and cell-ECM interactions. In addition, AML cells in our model possessed quiescent characteristics with improved chemoresistance attributes, resembling more the native conditions as indicated by our in vivo results. Moreover, the whole transcriptome data demonstrated the effect of 3D culture on enhancing BM niche cell characteristics. We identified molecular pathways upregulated in AML cells in our 3D model that might contribute to AML drug resistance and disease relapse. Conclusions Our results demonstrate the importance of developing 3D biomimicry models that closely recapitulate the in vivo conditions to gain deeper insights into drug resistance mechanisms and novel therapy development. These models can also improve personalized medicine by testing patient-specific treatments.

Boron adsorption mechanism of a hybrid gel derived from tetraethoxysilane and bis(trimethoxysilylpropyl)amine

Liu, H.,Qing, B.,Ye, X.,Guo, M.,Li, Q.,Wu, Z.,Lee, K.,Lee, D.,Lee, K. 한국물리학회 2009 Current Applied Physics Vol.9 No.4_SUP

An organic/inorganic hybrid gel was prepared with tetraethoxysilane (TEOS) and bis(trimethoxysilylpropyl)amine (TSPA) as precursors. The adsorption of boron on the hybrid gel in aqueous solutions was investigated comprehensively by varying the initial boron concentration, pH, ionic strength, and temperature. The equilibrium adsorption amount of boron increases with the increase in initial boron concentration and ionic strength, but decreases with the increase in temperature. The adsorption amount exhibits a maximum at initial pH of 4-10. Boron appears to be adsorbed in both H<SUB>3</SUB>BO<SUB>3</SUB> and B(OH)<SUB>4</SUB><SUP>-</SUP> forms through the hydrogen bonding, electrostatic and hydrophobic attractions.

Characteristics of alkali-resistant Ni/MgAl₂O₄ catalyst for direct internal reforming molten carbonate fuel cell

Park, D.S.,Li, Z.,Devianto, H.,Lee, H.I. Pergamon Press ; Elsevier Science Ltd 2010 INTERNATIONAL JOURNAL OF HYDROGEN ENERGY - Vol.35 No.11

Direct internal reforming - molten carbonate fuel cell (DIR-MCFC) has advantages of higher efficiency and smaller size. However, deactivation of the catalyst by alkali carbonate electrolytes poses a significant problem in MCFC. To solve this problem, Ni/MgO and Ni/MgAl<SUB>2</SUB>O<SUB>4</SUB> catalysts were compulsively mixed with a eutectic mixture of Li<SUB>2</SUB>CO<SUB>3</SUB> and Na<SUB>2</SUB>CO<SUB>3</SUB> prior to a methane steam reforming activity test. Activity of Ni/MgO rapidly decreased, while that of Ni/MgAl<SUB>2</SUB>O<SUB>4</SUB> remained steady due to good alkali resistance. To analyze the effects of alkali addition, N<SUB>2</SUB> adsorption-desorption, X-ray diffraction, temperature-programmed reduction and oxidation, scanning electron microscopy, and X-ray photoelectron spectroscopy experiments were carried out. Both Ni/MgO and Ni/MgAl<SUB>2</SUB>O<SUB>4</SUB> showed sintering of Ni and blocking of pores, which reduced the catalytic activity. However, Ni/MgAl<SUB>2</SUB>O<SUB>4</SUB> showed other positive effects such as stronger metal-support interaction and increased dissociative adsorption.

Microstructural Stability and Creep Performance of a Novel Low-Cost Single Crystal Superalloy

Z. H. Tan,X. G. Wang,Y. L. Du,Y. M. Li,Y. H. Yang,J. L. Liu,J. D. Liu,J. G. Li,Y. Z. Zhou,X. F. Sun 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.7

The increasing pursuit of advanced aero-engines with lower ratio between the cost and performance has greatly promotedthe demanding of single crystal superalloys characterized by low cost and outstanding temperature capability. In this study,a novel low-cost single crystal superalloy was designed and the creep tests as well as micro-characterization were carried outon the experimental alloy. The results illustrated that the novel single crystal alloy exhibited an ideal microstructural stabilitywithout precipitating TCP phases, after long-term thermal exposure at the ultimate service temperature of third generationsingle crystal superalloys. Moreover, the experimental alloy with only 3 wt% Re addition demonstrated remarkable creepresistance and maintained a very low minimum creep rate at 1100 °C/137 MPa and 1120 °C/137 MPa, while the accumulationand coalescence of micro-pores had eventually led to the alloy fracture. Apart from that, the compact interfacial dislocationnetworks the 2nd γ′ phase were observed after high-temperature creep rupture, and the typical a < 010 > superdislocationswith relatively poor mobility was found at 1120 °C. At 760 °C/800 MPa, both the minimum creep velocity and entire creepstain was increased evidently, however, the ultimate creep rupture life of the alloy had still reached 200 h. The correspondingdeformation mechanism was identified as the combination of superdislocation pairs shearing and a/3 < 121 > partial dislocationcutting the γ′ phase with a SISF being generated. In general, the novel single crystal alloy characterized by remarkablemechanical properties and cost reduction possesses a great potential for future application in the advanced aircraft engines.

Empirical Selection of Informative Microsatellite Markers within Co-ancestry Pig Populations Is Required for Improving the Individual Assignment Efficiency

Lia, Y.H.,Chu, H.P.,Jiang, Y.N.,Lin, C.Y.,Li, S.H.,Li, K.T.,Weng, G.J.,Cheng, C.C.,Lu, D.J.,Ju, Y.T. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.5

The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is distantly related to Asian and European pig breeds. It has been inbred to generate two breeds and crossed with Landrace and Duroc to produce two hybrids for laboratory use. Selecting sets of informative genetic markers to track the genetic qualities of laboratory animals and stud stock is an important function of genetic databases. For more than two decades, Lanyu derived breeds of common ancestry and crossbreeds have been used to examine the effectiveness of genetic marker selection and optimal approaches for individual assignment. In this paper, these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire, Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation Station Black pig are studied to build a genetic reference database. Nineteen microsatellite markers (loci) provide information on genetic variation and differentiation among studied breeds. High differentiation index ($F_{ST}$) and Cavalli-Sforza chord distances give genetic differentiation among breeds, including Lanyu's inbred populations. Inbreeding values ($F_{IS}$) show that Lanyu and its derived inbred breeds have significant loss of heterozygosity. Individual assignment testing of 352 animals was done with different numbers of microsatellite markers in this study. The testing assigned 99% of the animals successfully into their correct reference populations based on 9 to 14 markers ranking D-scores, allelic number, expected heterozygosity ($H_E$) or $F_{ST}$, respectively. All miss-assigned individuals came from close lineage Lanyu breeds. To improve individual assignment among close lineage breeds, microsatellite markers selected from Lanyu populations with high polymorphic, heterozygosity, $F_{ST}$ and D-scores were used. Only 6 to 8 markers ranking $H_E$, $F_{ST}$ or allelic number were required to obtain 99% assignment accuracy. This result suggests empirical examination of assignment-error rates is required if discernible levels of co-ancestry exist. In the reference group, optimum assignment accuracy was achievable achieved through a combination of different markers by ranking the heterozygosity, $F_{ST}$ and allelic number of close lineage populations.

A facile sol-gel method for synthesis of porous Nd-doped TiO₂ monolith with enhanced photocatalytic activity under UV-Vis irradiation

Du, J.,Chen, H.,Yang, H.,Sang, R.,Qian, Y.,Li, Y.,Zhu, G.,Mao, Y.,He, W.,Kang, D.J. Elsevier 2013 Microporous and mesoporous materials Vol.182 No.-

A porous Nd-doped TiO<SUB>2</SUB> monolith was successfully synthesized with polystyrene spheres as a template using a sol-gel method followed by calcination at high temperature. The porous Nd-doped TiO<SUB>2</SUB> monolith was characterized by X-ray diffractometry, scanning electron microscopy and Brunauer-Emmett-Teller measurements. Nd doping can increase the TiO<SUB>2</SUB> surface area by hindering the growth of large TiO<SUB>2</SUB> particles, and suppressing the recombination of photo-produced hole/electron (h<SUP>+</SUP>/e<SUP>-</SUP>) pairs. Moreover, its porous structure can provide a large surface area, facilitating enhanced adsorption and fast transfer of pollutants. To evaluate the photocatalytic activity of the porous Nd-doped TiO<SUB>2</SUB> monolith, the photo-degradation for methyl orange was investigated under UV-Vis irradiation. The porous 0.5% Nd-doped TiO<SUB>2</SUB> monolith showed better behavior than the other as-prepared samples and Degussa P25 due to its narrow band gap, high efficiency for h<SUP>+</SUP>/e<SUP>-</SUP> pair separation, and large surface area. The synergistic combination of Nd doping and the porous structure is a promising material design strategy for use in the degradation of organic pollutants.

China Spallation Neutron Source: Accelerator Design Iterations and R&D Status

J. Wei,C.-D. Deng,C.-H. Wang,C.-T. Shi,H. Sun,H.-F. Ouyang,H.-M. Qu,H.-Y. Dong,J. Li,J. Zhang,J.-S. Cao,J.-Y. Tang,L. Dong,L.-L. Wang,Q. Qin,Q.-B. Wang,S. Wang,S.-N. Fu,S.-X Fang,T. -G. Xu,W. Kang,Y.- 한국물리학회 2007 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.50 No.I

The China Spallation Neutron Source (CSNS) is a high-power, accelerator-based project currently under preparation. The accelerator complex consists of an H$^-$ ion source, an H$^-$ linac, a rapid-cycling proton synchrotron, and the transport lines. During the past year, the design of most accelerator systems went through major iterations, and initial research and developments was started on the prototyping of several key components.