Curcumin Analogue A501 induces G2/M Arrest and Apoptosis in Non-small Cell Lung Cancer Cells

Xia, Yi-Qun,Wei, Xiao-Yan,Li, Wu-Lan,Kanchana, Karvannan,Xu, Chao-Chao,Chen, Da-Hui,Chou, Pei-Hong,Jin, Rong,Wu, Jian-Zhang,Liang, Guang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Curcumin and its analogues have been reported to exert anti-cancer activity against a variety of tumors. Here, we reported A501, a new curcumin analogue. The effect of A501 on cell viability was detected by MTT assay, the result showed that A501 had a better inhibiting effect on the four non-small cell lung cancer (NSCLC) cells than that of curcumin. Moreover, Colony forming experiment showed A501 significant restrained cell proliferation. Flow cytometry displayed A501 can cause G2/M arrest and induce apoptosis. Western blotting showed that A501 decreased the expression of cyclinB1, cdc-2, bcl-2, while increased the expression of p53, cleaved caspase-3 and bax. In conclusion, curcumin analogues A501 played antitumor activity by inhibiting cell proliferation and inducing apoptosis of NSCLC cells. And it was likely to be a promising starting point for the development of curcumin-based anticancer drugs.

Unprotonated Short-Chain Alkylamines Inhibit Staphylolytic Activity of Lysostaphin in a Wall Teichoic Acid-Dependent Manner

Wu, Xia,Kwon, Seok Joon,Kim, Domyoung,Zha, Jian,Mora-Pale, Mauricio,Dordick, Jonathan S. American Society for Microbiology 2018 Applied and environmental microbiology Vol.84 No.14

<P>Lysostaphin (Lst) is a potent bacteriolytic enzyme that kills <I>Staphylococcus aureus</I>, a common bacterial pathogen of humans and animals. With high activity against both planktonic cells and biofilms, Lst has the potential to be used in industrial products, such as commercial cleansers, for decontamination. However, Lst is inhibited in the presence of monoethanolamine (MEA), a chemical widely used in cleaning solutions and pharmaceuticals, and the underlying mechanism of inhibition remains unknown. In this study, we examined the cell binding and killing capabilities of Lst against <I>S. aureus</I> ATCC 6538 in buffered salt solution with MEA at different pH values (7.5 to 10.5) and discovered that only the unprotonated form of MEA inhibited Lst binding to the cell surface, leading to low Lst activity, despite retention of its secondary structure. This reduced enzyme activity could be largely recovered via a reduction in wall teichoic acid (WTA) biosynthesis through tunicamycin treatment, indicating that the suppression of Lst activity was dependent on the presence and amount of WTA. We propose that the decreased cell binding and killing capabilities of Lst are associated with the influence of uncharged MEA on the conformation of WTA. A similar effect was confirmed with other short-chain alkylamines. This study offers new insight into the impact of short-chain alkylamines on both Lst and WTA structure and function and provides guidance for the application of Lst in harsh environments.</P><P><B>IMPORTANCE</B> Lysostaphin (Lst) effectively and selectively kills <I>Staphylococcus aureus</I>, the bacterial culprit of many hospital- and community-acquired skin and respiratory infections and food poisoning. Lst has been investigated in animal models and clinical trials, industrial formulations, and environmental settings. Here, we studied the mechanistic basis of the inhibitory effect of alkylamines, such as monoethanolamine (MEA), a widely used chemical in commercial detergents, on Lst activity, for the potential incorporation of Lst in disinfectant solutions. We have found that protonated MEA has little influence on Lst activity, while unprotonated MEA prevents Lst from binding to <I>S. aureus</I> cells and hence dramatically decreases the enzyme's bacteriolytic efficacy. Following partial removal of the wall teichoic acid, an important component of the bacterial cell envelope, the inhibitory effect of unprotonated MEA on Lst is reduced. This phenomenon can be extended to other short-chain alkylamines. This mechanistic report of the impact of alkylamines on Lst functionality will help guide future applications of Lst in disinfection and decontamination of health-related commercial products.</P>

Partial Least Squares Based Gene Expression Analysis in EBV-Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders

Wu, Sa,Zhang, Xin,Li, Zhi-Ming,Shi, Yan-Xia,Huang, Jia-Jia,Xia, Yi,Yang, Hang,Jiang, Wen-Qi Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

Effect of Ag Concentration and Annealing on the Optical Properties of Ag Nanoparticle Composite Films

Xia Wu,Jing Li,Jia-Ni Yu,Liang-Yao Chen,Peng Zhou,Shenjin Wei 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.49 No.5I

Scattering Model for Electrical-Large Target Employing MLFMA and Radar Imaging Formation

Xia Wu,Yaqiu Jin 한국전자파학회JEES 2010 Journal of Electromagnetic Engineering and Science Vol.10 No.3

To numerically calculate electromagnetic scattering from the electrical-large three-dimensional(3D) objects, the highfrequency approaches have been usually applied, but the accuracy and feasibility of these geometrical and physical optics(GO-PO) approaches, to some extent, are remained to be improved. In this paper, a new framework is developed for calculation of the near-field scattering field of an electrical-large 3D target by using a multilevel fast multipole algorithm(MLFMA) and generation of radar images by using a fast back-projection(FBP) algorithm. The MPI(Message Passing Interface) parallel computing is carried out to multiply the calculation efficiency greatly. Finally, a simple example of perfectly electrical conducting(PEC) patch and a canonical case of Fighting Falcon F-16 are presented.

Dynamic analysis of high-speed railway train-bridge system after barge collision

Xia, Chaoyi,Ma, Qin,Song, Fudong,Wu, Xuan,Xia, He Techno-Press 2018 Structural Engineering and Mechanics, An Int'l Jou Vol.67 No.1

In this paper, a framework is proposed for dynamic analysis of train-bridge systems with a damaged pier after barge collision. In simulating the barge-pier collision, the concrete pier is considered to be nonlinear-inelastic, and the barge-bow is modeled as elastic-plastic. The changes of dynamic properties and deformation of the damaged pier, and the additional unevenness of the track induced by the change of deck profile, are analyzed. The dynamic analysis model for train-bridge coupling system with a damaged pier is established. Based on the framework, an illustrative case study is carried out with a $5{\times}32m$ simply-supported PC box-girder bridge and the ICE3 high-speed train, to investigate the dynamic response of the bridge with a damaged pier after barge collision and its influence on the running safety of high-speed train. The results show that after collision by the barge, the vibration properties of the pier and the deck profile of bridge are changed, forming an additional unevenness of the track, by which the dynamic responses of the bridge and the car-body accelerations of the train are increased, and the running safety of high-speed train is affected.

Flexible Peptide Linkers Enhance the Antimicrobial Activity of Surface-Immobilized Bacteriolytic Enzymes

Wu, Xia,Fraser, Keith,Zha, Jian,Dordick, Jonathan S. American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.43

<P>Chemical linkers are frequently used in enzyme immobilization to improve enzyme flexibility and activity, whereas peptide linkers, although ubiquitous in protein engineering, are much less explored in enzyme immobilization. Here, we report peptide-linker-assisted noncovalent immobilization of the bacteriolytic enzyme lysostaphin (Lst) to generate anti-<I>Staphylococcus aureus</I> surfaces. Lst was immobilized through affinity tags onto a silica surface (glass slides) and nickel nitrilotriacetic acid (NiNTA) agarose beads via silica-binding peptides (SiBPs) or a hexahistidine tag (His-tag) fused at the C-terminus of Lst, respectively. By inserting specific peptide linkers upstream of the SiBP or His-tag, the immobilized enzymes killed >99.5% of <I>S. aureus</I> ATCC 6538 cells (10<SUP>8</SUP> CFU/mL) within 3 h in buffer and could be reused multiple times without significant loss of activity. In contrast, immobilized Lst without a peptide linker was less active/stable. Molecular modeling of Lst-linker-affinity tag constructs illustrated that the presence of the peptide linkers enhanced the molecular flexibility of the proximal Lst binding domain, which interacts with the bacterial substrate, and such increased flexibility correlated with increased antimicrobial activity. We further show that Lst immobilized onto NiNTA beads retained the ability to kill ∼99% of a 10<SUP>8</SUP> CFU/mL microbial challenge even in the presence of 1% of a commercial anionic surfactant, C12-14 alcohol EO 3:1 sodium sulfate, when the Lst construct contained a decapeptide linker containing glycine, serine, and alanine residues. This linker-assisted immobilization strategy could be extended to an unrelated lytic enzyme, the endolysin PlyPH, to target <I>Bacillus anthracis</I> Sterne cells either in buffer or in the presence of anionic surfactants. Our approach, therefore, provides a facile route to the use of antimicrobial enzymes on surfaces.</P> [FIG OMISSION]</BR>

Vitamin B6 Deficiency, Genome Instability and Cancer

Wu, Xia-Yu,Lu, Lin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Vitamin B6 functions as a coenzyme in >140 enzymatic reactions involved in the metabolism of amino acids, carbohydrates, neurotransmitters, and lipids. It comprises a group of three related 3-hydroxy-2-methyl-pyrimidine derivatives: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and their phosphorylated derivatives [pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP)], In the folate metabolism pathway, PLP is a cofactor for the mitochondrial and cytoplasmic isozymes of serine hydroxymethyltransferase (SHMT2 and SHMT1), the P-protein of the glycine cleavage system, cystathionine ${\beta}$-synthase (CBS) and ${\gamma}$-cystathionase, and betaine hydroxymethyltransferase (BHMT), all of which contribute to homocysteine metabolism either through folate-mediated one-carbon metabolism or the transsulfuration pathway. Folate cofactors carry and chemically activate single carbons for the synthesis of purines, thymidylate and methionine. So the evidence indicates that vitamin B6 plays an important role in maintenance of the genome, epigenetic stability and homocysteine metabolism. This article focuses on studies of strand breaks, micronuclei, or chromosomal aberrations regarding protective effects of vitamin B6, and probes whether it is folate-mediated one-carbon metabolism or the transsulfuration pathway for vitamin B6 which plays critical roles in prevention of cancer and cardiovascular disease.

vfr, A Global Regulatory Gene, is Required for Pyrrolnitrin but not for Phenazine-1-carboxylic Acid Biosynthesis in Pseudomonas chlororaphis G05

Xia Wu,Xiaoyan Chi,Yanhua Wang,Kailu Zhang,Le Kai,Qiuning He,Jinxiu Tang,Kewen Wang,Longshuo Sun,Xiuying Hao,Weihai Xie,Yihe Ge 한국식물병리학회 2019 Plant Pathology Journal Vol.35 No.4

In our previous study, pyrrolnitrin produced in Pseudomonas chlororaphis G05 plays more critical role in suppression of mycelial growth of some fungal pathogens that cause plant diseases in agriculture. Although some regulators for pyrrolnitrin biosynthesis were identified, the pyrrolnitrin regulation pathway was not fully constructed. During our screening novel regulator candidates, we obtained a white conjugant G05W02 while transposon mutagenesis was carried out between a fusion mutant G05ΔphzΔprn::lacZ and E. coli S17- 1 (pUT/mini-Tn5Kan). By cloning and sequencing of the transposon-flanking DNA fragment, we found that a vfr gene in the conjugant G05W02 was disrupted with mini-Tn5Kan. In one other previous study on P. fluorescens, however, it was reported that the deletion of the vfr caused increased production of pyrrolnitrin and other antifungal metabolites. To confirm its regulatory function, we constructed the vfr-knockout mutant G05Δvfr and G05ΔphzΔprn::lacZΔvfr. By quantifying β-galactosidase activities, we found that deletion of the vfr decreased the prn operon expression dramatically. Meanwhile, by quantifying pyrrolnitrin production in the mutant G05Δvfr, we found that deficiency of the Vfr caused decreased pyrrolnitrin production. However, production of phenazine-1-carboxylic acid was same to that in the wild-type strain G05. Taken together, Vfr is required for pyrrolnitrin but not for phenazine-1-carboxylic acid biosynthesis in P. chlororaphis G05.

Interactions Between MTHFR C677T - A1298C Variants and Folic Acid Deficiency Affect Breast Cancer Risk in a Chinese Population

Wu, Xia-Yu,Ni, Juan,Xu, Wei-Jiang,Zhou, Tao,Wang, Xu Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.