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Sample records for cycle inducing compounds

  1. Compound cycle engine program

    NASA Technical Reports Server (NTRS)

    Bobula, G. A.; Wintucky, W. T.; Castor, J. G.

    1986-01-01

    The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the lightweight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burned for a typical 2 hr (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. A program to establish the technology base for a Compound Cycle Engine is presented. The goal of this program is to research and develop those technologies which are barriers to demonstrating a multicylinder diesel core in the early 1990's. The major activity underway is a three-phased contract with the Garrett Turbine Engine Company to perform: (1) a light helicopter feasibility study, (2) component technology development, and (3) lubricant and material research and development. Other related activities are also presented.

  2. Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor

    SciTech Connect

    Fujii, Seiko; Okinaga, Toshinori; Ariyoshi, Wataru; Takahashi, Osamu; Iwanaga, Kenjiro; Nishino, Norikazu; Tominaga, Kazuhiro; Nishihara, Tatsuji

    2013-05-10

    Highlights: •Novel histone deacetylase inhibitor Ky-2, remarkably inhibits myeloma cell growth. •Ky-2 demonstrates no cytotoxicity against normal lymphocytic cells. •Ky-2 induces cell cycle arrest through the cell cycle-associated proteins. •Ky-2 induces Bcl-2-inhibitable apoptosis through a caspase-dependent cascade. -- Abstract: Objectives: Histone deacetylase (HDAC) inhibitors are new therapeutic agents, used to treat various types of malignant cancers. In the present study, we investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth of mouse myeloma cells. Materials and methods: Myeloma cells, HS-72, P3U1, and mouse normal cells were used in this study. Effect of HDAC inhibitors on cell viability was determined by WST-assay and trypan blue assay. Cell cycle was analyzed using flow cytometer. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis. Hoechst’s staining was used to detect apoptotic cells. Results: Our findings showed that Ky-2 decreased the levels of HDACs, while it enhanced acetylation of histone H3. Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2 had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase cell cycle arrest and accumulation of a sub-G1 phase population, while Western blotting analysis revealed that expressions of the cell cycle-associated proteins were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to induce apoptosis in bcl-2 overexpressing myeloma cells. Conclusion: These findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and Bcl-2-inhibitable mechanism in myeloma cells.

  3. Novel dichlorophenyl urea compounds inhibit proliferation of human leukemia HL-60 cells by inducing cell cycle arrest, differentiation and apoptosis.

    PubMed

    Figarola, James L; Weng, Yehua; Lincoln, Christopher; Horne, David; Rahbar, Samuel

    2012-08-01

    Two novel dichlorophenyl urea compounds, SR4 and SR9, were synthesized in our laboratory and evaluated for anti-cancer activities. Specifically, we investigated the antiproliferative properties of these new compounds on promyelocytic HL-60 leukemia cells by analyzing their effects on cell differentiation, cell cycle progression and apoptosis. SR4 and SR9 were both cytotoxic to HL-60 cells in a dose-and time-dependent manner, with IC(50) of 1.2 μM and 2.2 μM, respectively, after 72 h treatment. Both compounds strongly suppressed growth of HL-60 cells by promoting cell cycle arrest at the G0/G1 transition, with concomitant decrease in protein levels of cyclins D1 and E2 and cyclin-dependent kinases (CDK 2 and CDK 4), and increased protein expression of CDK inhibitors p21(WAF1/Cip1) and p27(Kip1). In addition, either compounds induce cell differentiation as detected by increased NBT staining and expression of CD11b and CD14. Treatment with SR compounds also promoted mitochondrial-dependent apoptosis as confirmed by Annexin V-FITC double staining, DNA fragmentation, increased expression of caspase 3, 7 and 9, cytochrome c release, PARP degradation, and collapse in mitochondrial membrane potential (ΔΨ(MT)). Collectively, these results provide evidence that SR4 and SR9 have the potential for the treatment of human leukemia and merit further investigation as therapeutic agents against other types of cancer. PMID:21728022

  4. Technology developments for a compound cycle engine

    NASA Technical Reports Server (NTRS)

    Bobula, George A.; Wintucky, William T.; Castor, J. G.

    1988-01-01

    The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the light weight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burned for a typical 2 hour (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. Results of recent activities in a program to establish the technology base for a CCE are presented. The objective of this program is to research and develop those critical technologies which are necessary for the demonstration of a multicylinder diesel core in the early 1990s. A major accomplishment was the initial screening and identification of a lubricant which has potential for meeting the material wear rate limits of the application. An in-situ wear measurement system also was developed to provide accurate, readily obtainable, real time measurements of ring and liner wear. Wear data, from early single cylinder engine tests, are presented to show correlation of the in-situ measurements and the system's utility in determining parametric wear trends. A plan to demonstrate a compound cycle engine by the mid 1990s is included.

  5. Compound cycle engine for helicopter application

    NASA Technical Reports Server (NTRS)

    Castor, Jere G.

    1986-01-01

    The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded, ultra-high power density, light-weight diesel engine. The turbomachinery is similar to a moderate pressure ratio, free power turbine engine and the diesel core is high speed and a low compression ratio. This engine is considered a potential candidate for future military light helicopter applications. This executive summary presents cycle thermodynamic (SFC) and engine weight analyses performed to establish general engine operating parameters and configuration. An extensive performance and weight analysis based on a typical two hour helicopter (+30 minute reserve) mission determined final conceptual engine design. With this mission, CCE performance was compared to that of a T-800 class gas turbine engine. The CCE had a 31% lower-fuel consumption and resulted in a 16% reduction in engine plus fuel and fuel tank weight. Design SFC of the CCE is 0.33 lb-HP-HR and installed wet weight is 0.43 lbs/HP. The major technology development areas required for the CCE are identified and briefly discussed.

  6. Compound cycle engine for helicopter application

    NASA Technical Reports Server (NTRS)

    Castor, Jere; Martin, John; Bradley, Curtiss

    1987-01-01

    The compound cycle engine (CCE) is a highly turbocharged, power-compounded, ultra-high-power-density, lightweight diesel engine. The turbomachinery is similar to a moderate-pressure-ratio, free-power-turbine gas turbine engine and the diesel core is high speed and a low compression ratio. This engine is considered a potential candidate for future military helicopter applications. Cycle thermodynamic specific fuel consumption (SFC) and engine weight analyses performed to establish general engine operating parameters and configurations are presented. An extensive performance and weight analysis based on a typical 2-hour helicopter (+30 minute reserve) mission determined final conceptual engine design. With this mission, CCE performance was compared to that of a contemporary gas turbine engine. The CCE had a 31 percent lower-fuel consumption and resulted in a 16 percent reduction in engine plus fuel and fuel tank weight. Design SFC of the CCE is 0.33 lb/hp-hr and installed wet weight is 0.43 lb/hp. The major technology development areas required for the CCE are identified and briefly discussed.

  7. Sparstolonin B, a Novel Plant Derived Compound, Arrests Cell Cycle and Induces Apoptosis in N-Myc Amplified and N-Myc Nonamplified Neuroblastoma Cells

    PubMed Central

    Kumar, Ambrish; Fan, Daping; DiPette, Donald J.; Singh, Ugra S.

    2014-01-01

    Neuroblastoma is one of the most common solid tumors and accounts for ∼15% of all the cancer related deaths in the children. Despite the standard therapy for advanced disease including chemotherapy, surgery, and radiation, the mortality rate remains high for these patients. Hence, novel therapeutic agents are desperately needed. Here we examined the anticancer activity of a novel plant-derived compound, sparstolonin B (SsnB; 8,5′-dihydroxy-4-phenyl-5,2′-oxidoisocoumarin) using neuroblastoma cell lines of different genetics. SsnB was recently isolated from an aquatic Chinese herb, Sparganium stoloniferum, and tubers of this herb have been used in traditional Chinese medicine for the treatment of several inflammatory diseases and cancers. Our cell viability and morphological analysis indicated that SsnB at 10 µM concentration significantly inhibited the growth of both N-myc amplified (SK-N-BE(2), NGP, and IMR-32 cells) and N-myc nonamplified (SH-SY5Y and SKNF-1 cells) neuroblastoma cells. The flow cytometric analyses suggested that SsnB arrests the cell cycle progression at G2-M phase in all neuroblastoma cell lines tested. Exposure of SsnB inhibited the compact spheroid formation and reduced the tumorigenicity of SH-SY5Y cells and SK-N-BE(2) cells in in vitro 3-D cell culture assays (anchorage-independent colony formation assay and hanging drop assay). SsnB lowers the cellular level of glutathione (GSH), increases generation of reactive oxygen species and activates the cleavage of caspase-3 whereas co-incubation of a GSH precursor, N-acetylcysteine, along with SsnB attenuates the inhibitory effects of SsnB and increases the neuroblastoma cell viability. Our results for the first time demonstrate that SsnB possesses anticancer activity indicating that SsnB-induced reactive oxygen species generation promotes apoptotic cell death in neuroblastoma cells of different genetic background. Thus these data suggest that SsnB can be a promising drug candidate in

  8. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

    SciTech Connect

    Gao Jiayu; Morgan, Winston A.; Sanchez-Medina, Alberto; Corcoran, Olivia

    2011-08-01

    Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G{sub 0}/G{sub 1} phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research Highlights: > Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. > Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. > Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. > Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

  9. The Thermodynamics of the Krebs Cycle and Related Compounds

    NASA Astrophysics Data System (ADS)

    Miller, Stanley L.; Smith-Magowan, David

    1990-07-01

    A survey is made of the enthalpies of formation, third law entropies and Gibbs energies available for Krebs cycle and related compounds. These include formate, acetate, succinate, fumarate, glycine, alanine, aspartate and glutamate. The potential of the NAD+/NADH couple is recalculated based on the ethanol/acetaldehyde and isopropanol/acetone equilibria. The reported enzyme catalyzed equilibrium constants of the Krebs cycle reactions are evaluated with estimated errors. These 28 equilibria form a network of reactions that is solved by a least squares regression procedure giving Gibbs energies of formation for 21 Krebs cycle and related compounds. They appear to be accurate to ±0.4 kJṡmol-1 for some compounds but ±1 kJṡmol-1 in less favorable cases. This procedure indicates which third law ΔfG and enzyme equilibria are inaccurate, and allows very accurate ΔfG to be determined for compounds related to the Krebs cycle by measuring enzyme equilibrium constants.

  10. Preliminary evaluation of a compound cycle engine for shipboard gensets

    NASA Technical Reports Server (NTRS)

    Castor, J. G.; Wintucky, W. T.

    1986-01-01

    The results of a thermodynamic cycle (SFC) and weight analysis performed to establish engine configuration, size, weight and performance are reported. Baseline design configuration was a 2,000 hour MTBO Compound Cycle Engine (CCE) for a helicopter application. The CCE configuration was extrapolated out to a 10,000 MTBO for a shipboard genset application. The study showed that an advanced diesel engine design (CCE) could be substantially lighter and smaller (79% and 82% respectively) than todays contemporary genset diesel engine. Although the CCE was not optimized, it had about a 7% reduction in mission fuel consumption over today's genset diesels. The CCE is a turbocharged, power-compounded, high power density, low-compression ratio diesel engine. Major technology development areas are presented.

  11. Preliminary evaluation of a compound cycle engine for shipboard gensets

    SciTech Connect

    Castor, J.G.; Wintucky, W.T.

    1986-06-01

    The results of a thermodynamic cycle (SFC) and weight analysis performed to establish engine configuration, size, weight and performance are reported. Baseline design configuration was a 2,000 hour MTBO Compound Cycle Engine (CCE) for a helicopter application. The CCE configuration was extrapolated out to a 10,000 MTBO for a shipboard genset application. The study showed that an advanced diesel engine design (CCE) could be substantially lighter and smaller (79% and 82% respectively) than todays contemporary genset diesel engine. Although the CCE was not optimized, it had about a 7% reduction in mission fuel consumption over today's genset diesels. The CCE is a turbocharged, power-compounded, high power density, low-compression ratio diesel engine. Major technology development areas are presented.

  12. Influence of sulfur compounds on the terrestrial carbon cycle

    NASA Astrophysics Data System (ADS)

    Eliseev, A. V.

    2015-11-01

    Using the climate model developed at the A.M. Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences (IAP RAS CM), numerical experiments have been conducted in line with the Coupled Model Intercomparison Project Phase 5 (CMIP5), but scaling the anthropogenic emissions of sulfur compounds into the troposphere by ±25%. Two types of impacts of sulfur compounds on climate and the global carbon cycle are considered: climate impact (CI, associated with the influence of tropospheric sulfates on climate and, as a consequence, on the carbon cycle characteristics) and ecological impact (EI, associated with the influence of SO2 on the rate of photosynthesis of terrestrial plants). The climate impact was found to be generally more important than the ecological one. However, in a number of regions, the EI is comparable to CI, including in the southeast parts of North America and, especially, of Asia. The contribution of EI to the change in global characteristics of terrestrial ecosystems in the 20th century is likewise considerable. The CI is generally more sensitive to the uncertainty in anthropogenic emissions of sulfur compounds into the troposphere than the EI.

  13. Metabolic Basis of Visual Cycle Inhibition by Retinoid and Nonretinoid Compounds in the Vertebrate Retina*

    PubMed Central

    Golczak, Marcin; Maeda, Akiko; Bereta, Grzegorz; Maeda, Tadao; Kiser, Philip D.; Hunzelmann, Silke; von Lintig, Johannes; Blaner, William S.; Palczewski, Krzysztof

    2008-01-01

    In vertebrate retinal photoreceptors, the absorption of light by rhodopsin leads to photoisomerization of 11-cis-retinal to its all-trans isomer. To sustain vision, a metabolic system evolved that recycles all-trans-retinal back to 11-cis-retinal. The importance of this visual (retinoid) cycle is underscored by the fact that mutations in genes encoding visual cycle components induce a wide spectrum of diseases characterized by abnormal levels of specific retinoid cycle intermediates. In addition, intense illumination can produce retinoid cycle by-products that are toxic to the retina. Thus, inhibition of the retinoid cycle has therapeutic potential in physiological and pathological states. Four classes of inhibitors that include retinoid and nonretinoid compounds have been identified. We investigated the modes of action of these inhibitors by using purified visual cycle components and in vivo systems. We report that retinylamine was the most potent and specific inhibitor of the retinoid cycle among the tested compounds and that it targets the retinoid isomerase, RPE65. Hydrophobic primary amines like farnesylamine also showed inhibitory potency but a short duration of action, probably due to rapid metabolism. These compounds also are reactive nucleophiles with potentially high cellular toxicity. We also evaluated the role of a specific protein-mediated mechanism on retinoid cycle inhibitor uptake by the eye. Our results show that retinylamine is transported to and taken up by the eye by retinol-binding protein-independent and retinoic acid-responsive gene product 6-independent mechanisms. Finally, we provide evidence for a crucial role of lecithin: retinol acyltransferase activity in mediating tissue specific absorption and long lasting therapeutic effects of retinoid-based visual cycle inhibitors. PMID:18195010

  14. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    SciTech Connect

    Huang, Shi-Wei; Wu, Chun-Ying; Wang, Yen-Ting; Kao, Jun-Kai; Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu; Chiu, Husan-Wen; Chang, Chuan-Hsun; Liang, Shu-Mei; Chen, Yi-Ju; Huang, Jau-Ling; Shieh, Jeng-Jer

    2013-02-15

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.

  15. Identification of Novel Small Organic Compounds with Diverse Structures for the Induction of Epstein-Barr Virus (EBV) Lytic Cycle in EBV-Positive Epithelial Malignancies

    PubMed Central

    Choi, Chung King; Ho, Dona N.; Hui, Kwai Fung; Kao, Richard Y.; Chiang, Alan K. S.

    2015-01-01

    Phorbol esters, which are protein kinase C (PKC) activators, and histone deacetylase (HDAC) inhibitors, which cause enhanced acetylation of cellular proteins, are the main classes of chemical inducers of Epstein-Barr virus (EBV) lytic cycle in latently EBV-infected cells acting through the PKC pathway. Chemical inducers which induce EBV lytic cycle through alternative cellular pathways may aid in defining the mechanisms leading to lytic cycle reactivation and improve cells’ responsiveness towards lytic induction. We performed a phenotypic screening on a chemical library of 50,240 novel small organic compounds to identify novel class(es) of strong inducer(s) of EBV lytic cycle in gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC) cells. Five hit compounds were selected after three successive rounds of increasingly stringent screening. All five compounds are structurally diverse from each other and distinct from phorbol esters or HDAC inhibitors. They neither cause hyperacetylation of histone proteins nor significant PKC activation at their working concentrations, suggesting that their biological mode of action are distinct from that of the known chemical inducers. Two of the five compounds with rapid lytic-inducing action were further studied for their mechanisms of induction of EBV lytic cycle. Unlike HDAC inhibitors, lytic induction by both compounds was not inhibited by rottlerin, a specific inhibitor of PKCδ. Interestingly, both compounds could cooperate with HDAC inhibitors to enhance EBV lytic cycle induction in EBV-positive epithelial cancer cells, paving way for the development of strategies to increase cells’ responsiveness towards lytic reactivation. One of the two compounds bears structural resemblance to iron chelators and the other strongly activates the MAPK pathways. These structurally diverse novel organic compounds may represent potential new classes of chemicals that can be used to investigate any alternative mechanism(s) leading to EBV

  16. Natural compounds as corrosion inhibitors for highly cycled systems

    SciTech Connect

    Quraishi, M.A.; Farooqi, I.H.; Saini, P.A.

    1999-11-01

    Strict environmental legislations have led to the development of green inhibitors in recent years. In continuation of the authors` research work on development of green inhibitors, they have investigated the aqueous extracts of three plants namely: Azadirachta indica, Punica Granatum and Momordica charantia as corrosion inhibitors for mild steel in 3% NaCl using weight loss and electrochemical methods. All the investigated compounds exhibited excellent corrosion inhibition properties comparable to that of HEDP. Azadirachta showed better scale inhibition effect than HEDP.

  17. Ligand modulation of a dinuclear platinum compound leads to mechanistic differences in cell cycle progression and arrest

    PubMed Central

    Menon, Vijay R.; Peterson, Erica J.; Valerie, Kristoffer; Farrell, Nicholas P.; Povirk, Lawrence F.

    2013-01-01

    Despite similar structures and DNA binding profiles, two recently synthesized dinuclear platinum compounds are shown to elicit highly divergent effects on cell cycle progression. In colorectal HCT116 cells, BBR3610 shows a classical G2/M arrest with initial accumulation in S phase, but the derivative compound BBR3610-DACH, formed by introduction of the 1,2-diaminocyclohexane (DACH) as carrier ligand, results in severe G1/S as well as G2/M phase arrest, with nearly complete S phase depletion. The origin of this unique effect was studied. Cellular interstrand crosslinking as assayed by comet analysis was similar for both compounds, confirming previous in vitro results obtained on plasmid DNA. Immunoblotting revealed a stabilization of p53 and concomitant transient increases in p21 and p27 proteins after treatment with BBR3610-DACH. Cell viability assays and cytometric analysis of p53 and p21 null cells indicated that BBR3610-DACH-induced cell cycle arrest was p21-dependent and partially p53-dependent. However, an increase in the levels of cyclin E was observed with steady state levels of CDK2 and Cdc25A, suggesting that the G1 block occurs downstream of CDK/cyclin complex formation. The G2/M block was corroborated with decreased levels of cyclin A and cyclin B1. Surprisingly, BBR3610-DACH-induced G1 block was independent of ATM and ATR. Finally, both compounds induced apoptosis, with BBR3610-DACH showing a robust PARP-1 cleavage that was not associated with caspase-3/7 cleavage. In summary, BBR3610-DACH is a DNA binding platinum agent with unique inhibitory effects on cell cycle progression that could be further developed as a chemotherapeutic agent complementary to cisplatin and oxaliplatin. PMID:24161784

  18. Analysis of cell death inducing compounds.

    PubMed

    Spicker, Jeppe S; Pedersen, Henrik Toft; Nielsen, Henrik Bjørn; Brunak, Søren

    2007-11-01

    Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different compounds, three toxins (ANIT, DMN and NMF) and three non-toxins (Caeruelein, Dinitrophenol and Rosiglitazone). We identified three gene transcripts with exceptional predictive performance towards liver toxicity and/or changes in histopathology. The three genes were: glucokinase regulatory protein (GCKR), ornithine aminotransferase (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29). RT-PCR for these three genes was performed and four additional compounds were included for validation. The quantitative RT-PCR analysis confirmed the findings based on the microarray data and using the three genes a classification rate of 55 of 57 samples was achieved for the classification of not toxic versus toxic. The single most promising biomarker (OAT) alone resulted in a surprisingly 100% correctly classified samples. OAT has not previously been linked to toxicity and cell death in the literature and the novel finding represents a putative hepatotoxicity biomarker. PMID:17503021

  19. Parvovirus infection-induced cell death and cell cycle arrest

    PubMed Central

    Chen, Aaron Yun; Qiu, Jianming

    2011-01-01

    The cytopathic effects induced during parvovirus infection have been widely documented. Parvovirus infection-induced cell death is often directly associated with disease outcomes (e.g., anemia resulting from loss of erythroid progenitors during parvovirus B19 infection). Apoptosis is the major form of cell death induced by parvovirus infection. However, nonapoptotic cell death, namely necrosis, has also been reported during infection of the minute virus of mice, parvovirus H-1 and bovine parvovirus. Recent studies have revealed multiple mechanisms underlying the cell death during parvovirus infection. These mechanisms vary in different parvoviruses, although the large nonstructural protein (NS)1 and the small NS proteins (e.g., the 11 kDa of parvovirus B19), as well as replication of the viral genome, are responsible for causing infection-induced cell death. Cell cycle arrest is also common, and contributes to the cytopathic effects induced during parvovirus infection. While viral NS proteins have been indicated to induce cell cycle arrest, increasing evidence suggests that a cellular DNA damage response triggered by an invading single-stranded parvoviral genome is the major inducer of cell cycle arrest in parvovirus-infected cells. Apparently, in response to infection, cell death and cell cycle arrest of parvovirus-infected cells are beneficial to the viral cell lifecycle (e.g., viral DNA replication and virus egress). In this article, we will discuss recent advances in the understanding of the mechanisms underlying parvovirus infection-induced cell death and cell cycle arrest. PMID:21331319

  20. Thermal Cycling Effects on the Thermoelectric Properties of n-Type In, Ce based Skutterudite Compounds

    SciTech Connect

    Biswas, Krishnendu; Subramanian, Mas A.; Good, Morris S.; Roberts, Kamandi C.; Hendricks, Terry J.

    2012-06-14

    N-type In-filled CoSb3 are known skutterudite compounds that have shown promising thermoelectric (TE) properties resulting in high dimensionless figure of merit values at elevated temperatures. Their use in various waste heat recovery applications will require that they survive and operate after exposure to harsh thermal cycling environments. This research focused on uncovering the thermal cycling effects on thermoelectric properties of n-type In0.2Co4Sb12 and In0.2Ce0.15Co4Sb12 skutterudite compositions as well as quantifying their temperature-dependent structural properties (elastic modulus, shear modulus, and Poisson's ratio). It was observed that the Seebeck coefficient and resistivity increased only slightly in the double-filled In,Ce skutterudite materials upon thermal cycling. In the In-filled skutterudites the Seebeck coefficient remained approximately the same on thermal cycling, while electrical resistivity increased significantly after thermal cycling. Results also show that thermal conductivity marginally decreases in the case of In-filled skutterudites, whereas the reduction is more pronounced in In, Ce-based skutterudite compounds. The possible reason for this kind of reduction can be attributed to grain pinning effects due to formation of nano inclusions. High temperature structural property measurements (i.e., Young's modulus and shear modulus) are also reported and the results show that these structural properties decrease slowly as temperature increases and the compounds are structurally stable after numerous thermal cycles.

  1. Valproic Acid Induces Antimicrobial Compound Production in Doratomyces microspores

    PubMed Central

    Zutz, Christoph; Bacher, Markus; Parich, Alexandra; Kluger, Bernhard; Gacek-Matthews, Agnieszka; Schuhmacher, Rainer; Wagner, Martin; Rychli, Kathrin; Strauss, Joseph

    2016-01-01

    One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called “cryptic,” often silenced, compounds. These putative metabolites could include novel bioactive compounds. Considerable effort is spent on methods to induce production of these “cryptic” metabolites. One approach is the use of small molecule effectors, potentially influencing chromatin landscape in fungi. We observed that the supernatant of the fungus Doratomyces (D.) microsporus treated with valproic acid (VPA) displayed antimicrobial activity against Staphylococcus (S.) aureus and two methicillin resistant clinical S. aureus isolates. VPA treatment resulted in enhanced production of seven antimicrobial compounds: cyclo-(L-proline-L-methionine) (cPM), p-hydroxybenzaldehyde, cyclo-(phenylalanine-proline) (cFP), indole-3-carboxylic acid, phenylacetic acid (PAA) and indole-3-acetic acid. The production of the antimicrobial compound phenyllactic acid was exclusively detectable after VPA treatment. Furthermore three compounds, cPM, cFP, and PAA, were able to boost the antimicrobial activity of other antimicrobial compounds. cPM, for the first time isolated from fungi, and to a lesser extent PAA, are even able to decrease the minimal inhibitory concentration of ampicillin in MRSA strains. In conclusion we could show in this study that VPA treatment is a potent tool for induction of “cryptic” antimicrobial compound production in fungi, and that the induced compounds are not exclusively linked to the secondary metabolism. Furthermore this is the first discovery of the rare diketopiperazine cPM in fungi. Additionally we could demonstrate that cPM and PAA boost antibiotic activity

  2. Induced natural convection thermal cycling device

    DOEpatents

    Heung, Leung Kit

    2002-08-13

    A device for separating gases, especially isotopes, by thermal cycling of a separation column using a pressure vessel mounted vertically and having baffled sources for cold and heat. Coils at the top are cooled with a fluid such as liquid nitrogen. Coils at the bottom are either electrical resistance coils or a tubular heat exchange. The sources are shrouded with an insulated "top hat" and simultaneously opened and closed at the outlets to cool or heat the separation column. Alternatively, the sources for cold and heat are mounted separately outside the vessel and an external loop is provided for each circuit.

  3. Prediction of thermal cycling induced matrix cracking

    NASA Technical Reports Server (NTRS)

    Mcmanus, Hugh L.

    1992-01-01

    Thermal fatigue has been observed to cause matrix cracking in laminated composite materials. A method is presented to predict transverse matrix cracks in composite laminates subjected to cyclic thermal load. Shear lag stress approximations and a simple energy-based fracture criteria are used to predict crack densities as a function of temperature. Prediction of crack densities as a function of thermal cycling is accomplished by assuming that fatigue degrades the material's inherent resistance to cracking. The method is implemented as a computer program. A simple experiment provides data on progressive cracking of a laminate with decreasing temperature. Existing data on thermal fatigue is also used. Correlations of the analytical predictions to the data are very good. A parametric study using the analytical method is presented which provides insight into material behavior under cyclical thermal loads.

  4. Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing cell cycle arrest.

    PubMed

    Zhang, Yusong; Zhuang, Zhixiang; Meng, Qinghui; Jiao, Yang; Xu, Jiaying; Fan, Saijun

    2014-01-01

    Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number of biological functions. However, the anticancer activity of PD has been poorly investigated. In the present study, thiazolyl blue tetrazolium bromide assay was used to evaluate the inhibitory effect of PD on cell growth. Cell cycle distribution and apoptosis were investigated by flow cytometry. In addition, the expression of several proteins associated with apoptosis and cell cycle were analyzed by western blot analysis. The results demonstrated that PD significantly inhibits the proliferation of A549 and NCI-H1975 lung cancer cell lines and causes dose-dependent apoptosis. Cell cycle analysis revealed that PD induces S phase cell cycle arrest. Western blot analysis showed that the expression of Bcl-2 decreased as that of Bax increased, and the expression of cyclin D1 was also suppressed. The results suggest that PD has potential therapeutic applications in the treatment of lung cancer. PMID:24348867

  5. The cardioprotective compound cloxyquin uncouples mitochondria and induces autophagy.

    PubMed

    Zhang, Jimmy; Nadtochiy, Sergiy M; Urciuoli, William R; Brookes, Paul S

    2016-01-01

    Mitochondrial quality control mechanisms have been implicated in protection against cardiac ischemia-reperfusion (IR) injury. Previously, cloxyquin (5-chloroquinolin-8-ol) was identified via phenotypic screening as a cardioprotective compound. Herein, cloxyquin was identified as a mitochondrial uncoupler in both isolated heart mitochondria and adult cardiomyocytes. Additionally, cardiomyocytes isolated from transgenic mice expressing green fluorescent protein-tagged microtubule-associated protein light chain 3 showed increased autophagosome formation with cloxyquin treatment. The autophagy inhibitor chloroquine abolished cloxyquin-induced cardioprotection in both cellular and perfused heart (Langendorff) models of IR injury. Finally, in an in vivo murine left anterior descending coronary artery occlusion model of IR injury, cloxyquin significantly reduced infarct size from 31.4 ± 3.4% to 16.1 ± 2.2%. In conclusion, the cardioprotective compound cloxyquin simultaneously uncoupled mitochondria and induced autophagy. Importantly, autophagy appears to be required for cloxyquin-induced cardioprotection. PMID:26519034

  6. Sister-chromatid exchanges and cell-cycle delay in Chinese hamster V79 cells treated with 9 organophosphorus compounds (8 pesticides and 1 defoliant).

    PubMed

    Chen, H H; Sirianni, S R; Huang, C C

    1982-03-01

    Significant increase of sister-chromatid exchanges (SCE) in V79 cells treated with 2 organophosphorus pesticides (OPP), fenthion and oxydemeton-methyl, was observed. The other 7 compounds (6 OPP and 1 defoliant) namely, amaze, azinphos-methyl, bolstar, DEF-defoliant, fensulfothion, monitor and nemacur caused no increase of SCE frequencies at the doses tested. All the compounds except fensulfothion and oxydemeton-methyl induced cell-cycle delay in varying degrees. Cell-cycle delay caused by an OPP was found to be dose-dependent. Based on these data as well as others reported, it would appear that OPP which induce no SCE increase and no or slight cell-cycle delay could be considered as good candidates to substitute the pesticides that have been found to be harmful to the environment. PMID:6211614

  7. Natural Compounds' Activity against Cancer Stem-Like or Fast-Cycling Melanoma Cells

    PubMed Central

    Majchrzak, Kinga; Hartman, Mariusz; Czyz, Malgorzata

    2014-01-01

    Background Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity. Consequently, both melanoma stem-like cells and their more differentiated progeny must be eradicated to achieve durable cure. By reevaluating compounds in heterogeneous melanoma populations, it might be possible to select compounds with activity not only against fast-cycling cells but also against cancer stem-like cells. Natural compounds were the focus of the present study. Methods We analyzed 120 compounds from The Natural Products Set II to identify compounds active against melanoma populations grown in an anchorage-independent manner and enriched with cells exerting self-renewing capacity. Cell viability, cell cycle arrest, apoptosis, gene expression, clonogenic survival and label-retention were analyzed. Findings Several compounds efficiently eradicated cells with clonogenic capacity and nanaomycin A, streptonigrin and toyocamycin were effective at 0.1 µM. Other anti-clonogenic but not highly cytotoxic compounds such as bryostatin 1, siomycin A, illudin M, michellamine B and pentoxifylline markedly reduced the frequency of ABCB5 (ATP-binding cassette, sub-family B, member 5)-positive cells. On the contrary, treatment with maytansine and colchicine selected for cells expressing this transporter. Maytansine, streptonigrin, toyocamycin and colchicine, even if highly cytotoxic, left a small subpopulation of slow-dividing cells unaffected. Compounds selected in the present study differentially altered the expression of melanocyte/melanoma specific microphthalmia-associated transcription factor (MITF) and proto-oncogene c-MYC. Conclusion Selected anti-clonogenic compounds might be further investigated as potential adjuvants targeting melanoma stem

  8. Lithium compound deposition on mesocarbon microbead anode of lithium ion batteries after long-term cycling.

    PubMed

    Yang, Lijie; Cheng, Xinqun; Gao, Yunzhi; Zuo, Pengjian; Ma, Yulin; Du, Chunyu; Shen, Bin; Cui, Yingzhi; Guan, Ting; Yin, Geping

    2014-08-13

    Lithium compound deposition on mesocarbon microbead (MCMB) anode after long-term cycling was studied in LiCoO2/MCMB battery. Lithium compound deposition did not generate on the activated MCMB anode, but it generated unevenly on the long-term cycled anode. Gray deposition composed of dendrites and particles was formed on the lower surface of the MCMB layer first, then on the upper surface. The deposition and MCMB layer peeled off from the current collector, and a bump was formed in the cycled anode. The exfoliation and thick deposition increased the ohmic resistance, film resistance, and charge transfer resistance of the cell and decreased the capacity significantly. Metallic lithium did not exist in either the upper or the lower deposition layer according to the results of X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), the discharge curve, and anode potential. The outer region of both the lower and the upper deposition layers consisted of Li2CO3, LiOH, ROCO2Li, and ROLi. The inner region of the etched lower deposition layer mainly consisted of Li2O, LiF, and Li2CO3, and that of the etched upper deposition layer mainly consisted of Li2CO3, ROCO2Li, ROLi, and LiF. Solid electrolyte interphase (SEI) film hindering the intercalation of lithium ions into carbon layers and LiCoO2 cathode providing lithium source for the deposition were the two reasons leading to the formation of lithium compound deposition during long-term cycles. Because SEI film on the lower surface of MCMB layer was thicker than that on the upper surface, lithium compound deposition generated on the lower surface first. PMID:25020035

  9. Xanthones from the Leaves of Garcinia cowa Induce Cell Cycle Arrest, Apoptosis, and Autophagy in Cancer Cells.

    PubMed

    Xia, Zhengxiang; Zhang, Hong; Xu, Danqing; Lao, Yuanzhi; Fu, Wenwei; Tan, Hongsheng; Cao, Peng; Yang, Ling; Xu, Hongxi

    2015-01-01

    Two new xanthones, cowaxanthones G (1) and H (2), and 23 known analogues were isolated from an acetone extract of the leaves of Garcinia cowa. The isolated compounds were evaluated for cytotoxicity against three cancer cell lines and immortalized HL7702 normal liver cells, whereby compounds 1, 5, 8, and 15-17 exhibited significant cytotoxicity. Cell cycle analysis using flow cytometry showed that 5 induced cell cycle arrest at the S phase in a dose-dependent manner, 1 and 16 at the G2/M phase, and 17 at the G1 phase, while 16 and 17 induced apoptosis. Moreover, autophagy analysis by GFP-LC3 puncta formation and western blotting suggested that 17 induced autophagy. Taken together, our results suggest that these xanthones possess anticancer activities targeting cell cycle, apoptosis, and autophagy signaling pathways. PMID:26102071

  10. Cell cycle control of polyomavirus-induced transformation.

    PubMed Central

    Chen, H H; Fluck, M M

    1993-01-01

    The cell cycle dependence of polyomavirus transformation was analyzed in infections of nonpermissive Fischer rat (FR3T3) cells released from G0. A 5- to 100-fold (average, ca. 20-fold) difference in relative frequency of transformation was found for cells infected in the early G1 phase of the cell cycle compared with cells infected in G2. Differences in the relative level of early viral gene expression in those two cell populations were equivalent to those obtained for transformation frequencies. The difference in transformation potential was accounted for only in part by a cell cycle control of viral adsorption (2- to 15-fold effect). Furthermore, in cells infected in the early G1 phase, viral gene expression was induced as a big synchronous burst of large transcripts of variable sizes, delayed till the G1 phase of the cell cycle after that in which infection took place. Thus, the results demonstrate that the abortive infection cycle of G0-released FR3T3 cells is cell cycle regulated at least at two steps: adsorption and another early step, nuclear transport, decapsidation, up to or including the transcription of the viral early genes. The cell cycle regulation of these steps results in a similar regulation of the abortive and stable transformation processes, although it is more pronounced for the latter. A model implicating c-fos and c-jun is proposed. Images PMID:8383223

  11. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells

    SciTech Connect

    Hu, Xiaolan; Zhang, Xianqi; Qiu, Shuifeng; Yu, Daihua; Lin, Shuxin

    2010-07-16

    Research highlights: {yields} Salidroside inhibits the growth of human breast cancer cells. {yields} Salidroside induces cell-cycle arrest of human breast cancer cells. {yields} Salidroside induces apoptosis of human breast cancer cell lines. -- Abstract: Recently, salidroside (p-hydroxyphenethyl-{beta}-D-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

  12. Emerging contaminants of public health significance as water quality indicator compounds in the urban water cycle.

    PubMed

    Pal, Amrita; He, Yiliang; Jekel, Martin; Reinhard, Martin; Gin, Karina Yew-Hoong

    2014-10-01

    The contamination of the urban water cycle (UWC) with a wide array of emerging organic compounds (EOCs) increases with urbanization and population density. To produce drinking water from the UWC requires close examination of their sources, occurrence, pathways, and health effects and the efficacy of wastewater treatment and natural attenuation processes that may occur in surface water bodies and groundwater. This paper researches in details the structure of the UWC and investigates the routes by which the water cycle is increasingly contaminated with compounds generated from various anthropogenic activities. Along with a thorough survey of chemicals representing compound classes such as hormones, antibiotics, surfactants, endocrine disruptors, human and veterinary pharmaceuticals, X-ray contrast media, pesticides and metabolites, disinfection-by-products, algal toxins and taste-and-odor compounds, this paper provides a comprehensive and holistic review of the occurrence, fate, transport and potential health impact of the emerging organic contaminants of the UWC. This study also illustrates the widespread distribution of the emerging organic contaminants in the different aortas of the ecosystem and focuses on future research needs. PMID:24972248

  13. Biotransformations Utilizing β-Oxidation Cycle Reactions in the Synthesis of Natural Compounds and Medicines

    PubMed Central

    Œwizdor, Alina; Panek, Anna; Milecka-Tronina, Natalia; Kołek, Teresa

    2012-01-01

    β-Oxidation cycle reactions, which are key stages in the metabolism of fatty acids in eucaryotic cells and in processes with a significant role in the degradation of acids used by microbes as a carbon source, have also found application in biotransformations. One of the major advantages of biotransformations based on the β-oxidation cycle is the possibility to transform a substrate in a series of reactions catalyzed by a number of enzymes. It allows the use of sterols as a substrate base in the production of natural steroid compounds and their analogues. This route also leads to biologically active compounds of therapeutic significance. Transformations of natural substrates via β-oxidation are the core part of the synthetic routes of natural flavors used as food additives. Stereoselectivity of the enzymes catalyzing the stages of dehydrogenation and addition of a water molecule to the double bond also finds application in the synthesis of chiral biologically active compounds, including medicines. Recent advances in genetic, metabolic engineering, methods for the enhancement of bioprocess productivity and the selectivity of target reactions are also described. PMID:23443116

  14. Biotransformations utilizing β-oxidation cycle reactions in the synthesis of natural compounds and medicines.

    PubMed

    Swizdor, Alina; Panek, Anna; Milecka-Tronina, Natalia; Kołek, Teresa

    2012-01-01

    β-Oxidation cycle reactions, which are key stages in the metabolism of fatty acids in eucaryotic cells and in processes with a significant role in the degradation of acids used by microbes as a carbon source, have also found application in biotransformations. One of the major advantages of biotransformations based on the β-oxidation cycle is the possibility to transform a substrate in a series of reactions catalyzed by a number of enzymes. It allows the use of sterols as a substrate base in the production of natural steroid compounds and their analogues. This route also leads to biologically active compounds of therapeutic significance. Transformations of natural substrates via β-oxidation are the core part of the synthetic routes of natural flavors used as food additives. Stereoselectivity of the enzymes catalyzing the stages of dehydrogenation and addition of a water molecule to the double bond also finds application in the synthesis of chiral biologically active compounds, including medicines. Recent advances in genetic, metabolic engineering, methods for the enhancement of bioprocess productivity and the selectivity of target reactions are also described. PMID:23443116

  15. Pressure induced phase transitions in ceramic compounds containing tetragonal zirconia

    SciTech Connect

    Sparks, R.G.; Pfeiffer, G.; Paesler, M.A.

    1988-12-01

    Stabilized tetragonal zirconia compounds exhibit a transformation toughening process in which stress applied to the material induces a crystallographic phase transition. The phase transition is accompanied by a volume expansion in the stressed region thereby dissipating stress and increasing the fracture strength of the material. The hydrostatic component of the stress required to induce the phase transition can be investigated by the use of a high pressure technique in combination with Micro-Raman spectroscopy. The intensity of Raman lines characteristic for the crystallographic phases can be used to calculate the amount of material that has undergone the transition as a function of pressure. It was found that pressures on the order of 2-5 kBar were sufficient to produce an almost complete transition from the original tetragonal to the less dense monoclinic phase; while a further increase in pressure caused a gradual reversal of the transition back to the original tetragonal structure.

  16. α-Mangostin Induces Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma Cell

    PubMed Central

    Kwak, Hyun-Ho; Park, Bong-Soo

    2016-01-01

    Mangosteen has long been used as a traditional medicine and is known to have antibacterial, antioxidant, and anticancer effects. Although the effects of α-mangostin, a natural compound extracted from the pericarp of mangosteen, have been investigated in many studies, there is limited data on the effects of the compound in human oral squamous cell carcinoma (OSCC). In this study, α-mangostin was assessed as a potential anticancer agent against human OSCC cells. α-Mangostin inhibited cell proliferation and induced cell death in OSCC cells in a dose- and time-dependent manner with little to no effect on normal human PDLF cells. α-Mangostin treatment clearly showed apoptotic evidences such as nuclear fragmentation and accumulation of annexin V and PI-positive cells on OSCC cells. α-Mangostin treatment also caused the collapse of mitochondrial membrane potential and the translocation of cytochrome c from the mitochondria into the cytosol. The expressions of the mitochondria-related proteins were activated by α-mangostin. Treatment with α-mangostin also induced G1 phase arrest and downregulated cell cycle-related proteins (CDK/cyclin). Hence, α-mangostin specifically induces cell death and inhibits proliferation in OSCC cells via the intrinsic apoptosis pathway and cell cycle arrest at the G1 phase, suggesting that α-mangostin may be an effective agent for the treatment of OSCC. PMID:27478478

  17. Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest.

    PubMed

    Rai, Prashant; He, Fang; Kwang, Jimmy; Engelward, Bevin P; Chow, Vincent T K

    2016-01-01

    Streptococcus pneumoniae produces pneumolysin toxin as a key virulence factor against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin that forms lytic pores in host membranes and mediates pneumococcal disease pathogenesis by modulating inflammatory responses. Here, we show that pneumolysin, which is released during bacterial lysis, induces DNA double strand breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX phosphorylation (γH2AX). Pneumolysin-induced γH2AX foci recruit mediator of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end joining is inhibited. Further, we observe that cells that were undergoing DNA replication harbored DSBs in greater frequency during pneumolysin treatment. This observation raises the possibility that DSBs might be arising as a result of replication fork breakdown. Additionally, neutralizing the oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA damage and also cell cycle arrest, indicating that pneumolysin oligomerization is important for causing DNA damage. Taken together, this study reveals a previously unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with implications in the pathophysiology of S. pneumoniae infection. PMID:27026501

  18. Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest

    PubMed Central

    Rai, Prashant; He, Fang; Kwang, Jimmy; Engelward, Bevin P.; Chow, Vincent T.K.

    2016-01-01

    Streptococcus pneumoniae produces pneumolysin toxin as a key virulence factor against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin that forms lytic pores in host membranes and mediates pneumococcal disease pathogenesis by modulating inflammatory responses. Here, we show that pneumolysin, which is released during bacterial lysis, induces DNA double strand breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX phosphorylation (γH2AX). Pneumolysin-induced γH2AX foci recruit mediator of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end joining is inhibited. Further, we observe that cells that were undergoing DNA replication harbored DSBs in greater frequency during pneumolysin treatment. This observation raises the possibility that DSBs might be arising as a result of replication fork breakdown. Additionally, neutralizing the oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA damage and also cell cycle arrest, indicating that pneumolysin oligomerization is important for causing DNA damage. Taken together, this study reveals a previously unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with implications in the pathophysiology of S. pneumoniae infection. PMID:27026501

  19. Hair cycle control by leptin as a new anagen inducer.

    PubMed

    Sumikawa, Yasuyuki; Inui, Shigeki; Nakajima, Takeshi; Itami, Satoshi

    2014-01-01

    Our purpose is to clarify the physiological role of leptin in hair cycle as leptin reportedly causes activation of Stat3, which is indispensable for hair cycling. While hair follicles in dorsal skin of 5-week-old C57/BL6 mice had progressed to late anagen phase, those in dorsal skin of 5-week-old leptin receptor deficient db/db mice remained in the first telogen and later entered the anagen at postnatal day 40, indicating that deficiency in leptin receptor signalling delayed the second hair cycle progression. Next, we shaved dorsal hairs on wild-type mice at postnatal 7 weeks and injected skin with mouse leptin or a mock. After 20 days, although mock injection showed no effect, hair growth occurred around leptin injection area. Human leptin fragment (aa22-56) had similar effects. Although the hair cycle of ob/ob mice was similar to that of wild-type mice, injection of mouse leptin on ob/ob mice at postnatal 7 weeks induced anagen transition. Immunohistochemically, leptin is expressed in hair follicles from catagen to early anagen in wild-type mice, suggesting that leptin is an anagen inducer in vivo. Phosphorylation of Erk, Jak2 and Stat3 in human keratinocytes was stimulated by leptin and leptin fragment. In addition, RT-PCR and ELISA showed that the production of leptin by human dermal papilla cells increased under hypoxic condition, suggesting that hypoxia in catagen/telogen phase promotes leptin production, preparing for entry into the next anagen. In conclusion, leptin, a well-known adipokine, acts as an anagen inducer and represents a new player in hair biology. PMID:24237265

  20. Paeoniflorin, a novel heat shock protein–inducing compound

    PubMed Central

    Yan, Dai; Saito, Kiyoto; Ohmi, Yuri; Fujie, Noriyo; Ohtsuka, Kenzo

    2004-01-01

    Heat shock proteins (HSPs) are induced by various physical, chemical, and biological stresses. HSPs are known to function as molecular chaperones, and they not only regulate various processes of protein biogenesis but also function as lifeguards against proteotoxic stresses. Because it is very useful to discover nontoxic chaperone-inducing compounds, we searched for them in herbal medicines. Some herbal medicines had positive effects on the induction of HSPs (Hsp70, Hsp40, and Hsp27) in cultured mammalian cells. We next examined 2 major constituents of these herbal medicines, glycyrrhizin and paeoniflorin, with previously defined chemical structures. Glycyrrhizin had an enhancing effect on the HSP induction by heat shock but could not induce HSPs by itself. In contrast, paeoniflorin had not only an enhancing effect but also an inducing effect by itself on HSP expression. Thus, paeoniflorin might be termed a chaperone inducer and glycyrrhizin a chaperone coinducer. Treatment of cells with paeoniflorin but not glycyrrhizin resulted in enhanced phosphorylation and acquisition of the deoxyribonucleic acid–binding ability of heat shock transcription factor 1 (HSF1), as well as the formation of characteristic HSF1 granules in the nucleus, suggesting that the induction of HSPs by paeoniflorin is mediated by the activation of HSF1. Also, thermotolerance was induced by treatment with paeoniflorin but not glycyrrhizin. Paeoniflorin had no toxic effect at concentrations as high as 80 μg/ mL (166.4 μM). To our knowledge, this is the first report on the induction of HSPs by herbal medicines. PMID:15633296

  1. Modeling and remote sensing of human induced water cycle change

    NASA Astrophysics Data System (ADS)

    Pokhrel, Yadu N.

    2016-04-01

    The global water cycle has been profoundly affected by human land-water management especially during the last century. Since the changes in water cycle can affect the functioning of a wide range of biophysical and biogeochemical processes of the Earth system, it is essential to account for human land-water management in land surface models (LSMs) which are used for water resources assessment and to simulate the land surface hydrologic processes within Earth system models (ESMs). During the last two decades, noteworthy progress has been made in modeling human impacts on the water cycle but sufficient advancements have not yet been made, especially in representing human factors in large-scale LSMs toward integrating them into ESMs. In this study, an integrated modeling framework of continental-scale water cycle, with explicit representation of climate and human induced forces (e.g., irrigation, groundwater pumping) is developed and used to reconstruct the observed water cycle changes in the past and to attribute the observed changes to climatic and human factors. The new model builds upon two different previously developed models: a global LSM called the Human Impacts and GroundWater in the MATSIRO (HiGW-MAT) and a high-resolution regional groundwater model called the LEAF-Hydro-Flood. The model is used to retro-simulate the hydrologic stores and fluxes in close dialogue with in-situ and GRACE satellite based observations at a wide range of river basin scales around the world, with a particular focus on the changes in groundwater dynamics in northwest India, Pakistan, and the High Plains and Central Valley aquifers in the US.

  2. Irradiation-induced changes in nuclear shape and cell cycle

    SciTech Connect

    Iwata, M.; Sasaki, H.; Kishino, Y.; Tsuboi, T.; Sugishita, T.; Hosokawa, T.

    1982-03-01

    Using human uterine cervical carcinoma cells transplanted in nude mice and mice leukemia L5178Y cells, changes in the cell cycle following irradiation were observed by flow cytometry (FCM), and changes in the cell nuclei during the course of irradiation were measured by FCM. Experiments in vivo as well as in vitro caused accumulation of cells in the G2 to M populations, resulting in the so-called G2 block phenomenon as revealed by FCM analysis of DNA distributions. The radiation-induced changes of nuclear shapes were dependent on abnormal mitoses, which occurred more frequently in the G2 to M phases. Therefore it is suggested that the G2 block phenomenon plays an important role in radiation-induced cell death because the process of cell death by irradiation has been shown to proceed via these abnormal mitoses.

  3. A DNA-damage-induced cell cycle checkpoint in Arabidopsis.

    PubMed Central

    Preuss, S B; Britt, A B

    2003-01-01

    Although it is well established that plant seeds treated with high doses of gamma radiation arrest development as seedlings, the cause of this arrest is unknown. The uvh1 mutant of Arabidopsis is defective in a homolog of the human repair endonuclease XPF, and uvh1 mutants are sensitive to both the toxic effects of UV and the cytostatic effects of gamma radiation. Here we find that gamma irradiation of uvh1 plants specifically triggers a G(2)-phase cell cycle arrest. Mutants, termed suppressor of gamma (sog), that suppress this radiation-induced arrest and proceed through the cell cycle unimpeded were recovered in the uvh1 background; the resulting irradiated plants are genetically unstable. The sog mutations fall into two complementation groups. They are second-site suppressors of the uvh1 mutant's sensitivity to gamma radiation but do not affect the susceptibility of the plant to UV radiation. In addition to rendering the plants resistant to the growth inhibitory effects of gamma radiation, the sog1 mutation affects the proper development of the pollen tetrad, suggesting that SOG1 might also play a role in the regulation of cell cycle progression during meiosis. PMID:12750343

  4. Prediction of thermal cycling induced cracking in polmer matrix composites

    NASA Technical Reports Server (NTRS)

    Mcmanus, Hugh L.

    1994-01-01

    The work done in the period August 1993 through February 1994 on the 'Prediction of Thermal Cycling Induced Cracking In Polymer Matrix Composites' program is summarized. Most of the work performed in this period, as well as the previous one, is described in detail in the attached Master's thesis, 'Analysis of Thermally Induced Damage in Composite Space Structures,' by Cecelia Hyun Seon Park. Work on a small thermal cycling and aging chamber was concluded in this period. The chamber was extensively tested and calibrated. Temperatures can be controlled very precisely, and are very uniform in the test chamber. Based on results obtained in the previous period of this program, further experimental progressive cracking studies were carried out. The laminates tested were selected to clarify the differences between the behaviors of thick and thin ply layers, and to explore other variables such as stacking sequence and scaling effects. Most specimens tested were made available from existing stock at Langley Research Center. One laminate type had to be constructed from available prepreg material at Langley Research Center. Specimens from this laminate were cut and prepared at MIT. Thermal conditioning was carried out at Langley Research Center, and at the newly constructed MIT facility. Specimens were examined by edge inspection and by crack configuration studies, in which specimens were sanded down in order to examine the distribution of cracks within the specimens. A method for predicting matrix cracking due to decreasing temperatures and/or thermal cycling in all plies of an arbitrary laminate was implemented as a computer code. The code also predicts changes in properties due to the cracking. Extensive correlations between test results and code predictions were carried out. The computer code was documented and is ready for distribution.

  5. Oxime-induced reactivation of carboxylesterase inhibited by organophosphorus compounds

    SciTech Connect

    Maxwell, D.M.; Lieske, C.N.; Brecht, K.M.

    1993-05-13

    A structure-activity analysis of the ability of oximes to reactivate rat plasma carboxylesterase (CaE) that was inhibited by organophosphorus (OP) compounds revealed that uncharged oximes, such as diacetylmonoxime or monoisonitrosoacetone, were better reactivators than cationic oximes. Cationic oximes that are excellent reactivators of OP-inhibited acetylcholinesteraser such as pyridinium-2-aldoxime or the bis-pyridinium oximes, HI-6 and TMB-4, produced poor reactivation of OP-inhibited CaE. The best uncharged reactivator was diacetylmonoxime which produced complete reactivation at 0.3 mM in 2 hr of CaE that was inhibited by organophosphinates, alkoxy-containing phosphates, and alkoxy-containing phosphonates. Complete reactivation of CaE could be achieved even after inhibition by phosphonates with highly branched alkoxy groups, such as sarin and soman, that undergo rapid aging with acetylcholinesterase. CaE that was inhibited by phosphonates or phosphates that contained aryloxy groups were reactivated to a lower extent. The cause of this decreased reactivation appears to be an oxime-induced aging reaction that competes with the reactivation reaction. This oxime-induced aging reaction is accelerated by electron-withdrawing substituents on the aryloxy groups of phosphonates and by the presence of multiple aryloxy groups on phosphates. Thus, reactivation and aging of OP-inhibited CaE differ from the same processes for OP-inhibited acetylcholinesterase in both their oxime specificity and inhibitor specificity and, presumably, in their underlying mechanisms.

  6. Diosgenin induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma cells.

    PubMed

    Li, Yongjian; Wang, Xiaorong; Cheng, Silu; Du, Juan; Deng, Zhengting; Zhang, Yani; Liu, Qun; Gao, Jingdong; Cheng, Binbin; Ling, Changquan

    2015-02-01

    Diosgenin is a major compound of Dioscoreaceae plants such as yam, which is used as a drug in Traditional Chinese Medicine, and a common vegetable worldwide. The anticancer effect of diosgenin has been reported in various tumor cells, including leukemia, gastric, colorectal, and breast cancer. However, the activity of diosgenin on hepatocellular carcinoma (HCC) and the underlying mechanism have not been completely investigated. Therefore, we investigated the efficacy and associated mechanisms of diosgenin in HCC cells. Flow cytometric analysis was performed to determine the presence of cell cycle arrest and apopotic cells. Diosgenin significantly inhibited the growth of Bel-7402, SMMC-7721 and HepG2 HCC cells in a concentration-dependent manner. Diosgenin treatment for 24 h induced G2/M cell cycle arrest and apoptosis of hepatoma cells. Diosgenin inhibited Akt phosphorylation and upregulated p21 and p27 expression, but did not alter the expression of p53, suggesting diosgenin-induced upregulation of p21 and p57 is p53-independent in HCC cells. Diosgenin induced HCC cell apoptosis by activating caspase cascades -3, -8 and -9. However, diosgenin did not affect Bcl-2 and Bax levels. In conclusion, results of the present study suggest that diosgenin may be an active anti-HCC agent obtained from natural plants and provide new insights in understanding the mechanisms of diosgenin. PMID:25434486

  7. Cucurbitacins as inducers of cell death and a rich source of potential anticancer compounds.

    PubMed

    Ríos, J L; Andújar, I; Escandell, J M; Giner, R M; Recio, M C

    2012-01-01

    Triterpenes have been reported to induce cell death. One relevant group of this family of compounds is cucurbitacins, which have been studied as inducers of apoptosis in various cancer cell lines. The most significant mechanisms with regard to the apoptotic effects of cucurbitacins are their ability to modify transcriptional activities via nuclear factors or genes and their capability to activate or inhibit pro- or anti-apoptotic proteins. Still, while the majority of studies on these compounds have dealt with their apoptotic effects on cancer cell lines, several research groups have also explored their anti-inflammatory activities. In general, cucurbitacins are considered to be selective inhibitors of the JAK/STAT pathways; however, other mechanisms may be implicated in their apoptotic effects, including the MAPK pathway (known to be important for cancer cell proliferation and survival), PARP cleavage, expression of active caspase-3, decreased pSTAT3 and JAK3 levels, as well as decreases in various downstream STAT3 targets such as Mcl-1, Bcl-2, Bcl-xL, and cyclin D3, all of which are implicated in apoptosis and the cell cycle. Taking all these effects into account, cucurbitacins may prove useful in the treatment of different kinds of cancers, especially when used with other cytostatic agents. PMID:22443631

  8. Compounds of the upper gastrointestinal tract induce rapid and efficient excystation of Entamoeba invadens

    PubMed Central

    Mitra, Biswa Nath; Pradel, Gabriele; Frevert, Ute; Eichinger, Daniel

    2010-01-01

    The infective stage of Entamoeba parasites is an encysted form. This stage can be readily generated in vitro, which has allowed identification of stimuli that trigger the differentiation of the parasite trophozoite stage into the cyst stage. Studies of the second differentiation event, emergence of the parasite from the cyst upon infection of a host, have been hampered by the lack of an efficient means to excyst the parasite and complete the life cycle in vitro. We have determined that a combination of exposures to water, bicarbonate and bile induces rapid excystment of Entamoeba invadens cysts. The high efficiency of this method has allowed the visualization of the dynamics of the process by electron and confocal microscopy, and should permit the analysis of stage-specific gene expression and high through-put screening of inhibitory compounds. PMID:20018192

  9. The Impacts of Climate-Induced Drought on Biogeochemical Cycles

    NASA Astrophysics Data System (ADS)

    Peng, C.

    2014-12-01

    Terrestrial ecosystems and, in particular, forests exert strong controls on the global biogeochemical cycles and influence regional hydrology and climatology directly through water and surface energy budgets. Recent studies indicated that forest mortality caused by rising temperature and drought from around the world have unexpectedly increased in the past decade and they collectively illustrate the vulnerability of many forested ecosystems to rapid increases in tree mortality due to warmer temperatures and more severe drought. Persistent changes in tree mortality rates can alter forest structure, composition, and ecosystem services (such as albedo and carbon sequestration). Quantifying potential impacts of tree mortality on ecosystem processes requires research into mortality effects on carbon, energy, and water budgets at both site and regional levels. Despite recent progress, the uncertainty around mortality responses still limits our ability to predict the likelihood and anticipate the impacts of tree die-off. Studies are needed that explore tree death physiology for a wide variety of functional types, connect patterns of mortality with climate events, and quantify the impacts on carbon, energy, and water flux. In this presentation, I will highlight recent research progress, and identify key research needs and future challenges to predict the consequence and impacts of drought-induced large-scale forest mortality on biogeochemical cycles. I will focus on three main forest ecosystems (tropic rainforest in Amazon, temperate forest in Western USA, and boreal forest in Canada) as detailed case studies.

  10. Interannual Variations of MLS Carbon Monoxide Induced by Solar Cycle

    NASA Technical Reports Server (NTRS)

    Lee, Jae N.; Wu, Dong L.; Ruzmaikin, Alexander

    2013-01-01

    More than eight years (2004-2012) of carbon monoxide (CO) measurements from the Aura Microwave Limb Sounder (MLS) are analyzed. The mesospheric CO, largely produced by the carbon dioxide (CO2) photolysis in the lower thermosphere, is sensitive to the solar irradiance variability. The long-term variation of observed mesospheric MLS CO concentrations at high latitudes is likely driven by the solar-cycle modulated UV forcing. Despite of different CO abundances in the southern and northern hemispheric winter, the solar-cycle dependence appears to be similar. This solar signal is further carried down to the lower altitudes by the dynamical descent in the winter polar vortex. Aura MLS CO is compared with the Solar Radiation and Climate Experiment (SORCE) total solar irradiance (TSI) and also with the spectral irradiance in the far ultraviolet (FUV) region from the SORCE Solar-Stellar Irradiance Comparison Experiment (SOLSTICE). Significant positive correlation (up to 0.6) is found between CO and FUVTSI in a large part of the upper atmosphere. The distribution of this positive correlation in the mesosphere is consistent with the expectation of CO changes induced by the solar irradiance variations.

  11. Oxime-induced reactivation of carboxylesterase inhibited by organophosphorus compounds

    SciTech Connect

    Maxwell, D.M.; Lieske, C.N.; Brecht, K.M.

    1994-06-01

    A structure-activity analysis of the ability of oximes to reactivate rat plasma carboxylesterase (CaE) that was inhibited by organophosphorus (OP) compounds revealed that uncharged oximes, such as 2,3-butanedione monoxime (diacetylmonoxime) or monoisonitrosoacetone, were better reactivators than cationic oximes. Cationic oximes that are excellent reactivators of OP-inhibited acetylcholinesterase, such as pyridine-2-aldoxime or the bis-pyridine aldoximes, HI-6 and TMB. 4, produced poor reactivation of OP-inhibited CaE. The best uncharged reactivator was 2,3. butanedione monoxime, which produced complete reactivation at 0.3 mM in 2 h of CaE that was inhibited by phosphinates, alkoxy-containing phosphates, and alkoxy-containing phosphonates. Complete reactivation of CaE could be achieved even after inhibition by phosphonates with highly branched alkoxy groups, such as sarin and soman, that undergo rapid aging with acetylcholinesterase. CaE that was inhibited by phosphonates or phosphates that contained aryloxy groups were reactivated to a lesser extent. The cause of this decreased reactivation appears to be an oxime-induced aging reaction that competes with the reactivation reaction. This oxime-induced aging reaction is accelerated by electron-withdrawing substituents on the aryloxy groups of phosphonates and by the presence of multiple aryloxy groups on phosphates. Thus, reactivation and aging of OP-inhibited CaE differ from the same processes for OP- inhibited acetylcholinesterase in both their oxime specificity and inhibitor specificity and, presumably, in their underlying mechanisms.

  12. Non Equilibrium Transformations of Molecular Compounds Induced Mechanically

    SciTech Connect

    Descamps, M.; Willart, J. F.; Dudognon, E.

    2006-05-05

    Results clarifying the effects of mechanical milling on molecular solids are shortly reviewed. Special attention has been paid to the temperature of milling with regard to the glass transition temperature of the compounds. It is shown that decreasing the grinding temperature has for incidence to increase the amorphization tendency whereas milling above Tg produces a crystal-to-crystal transformation between polymorphic varieties. These observations contradict the usual proposition that grinding transforms the physical state only by a heating effect which induces a local melting. Equilibrium thermodynamics does not seem to be appropriate for describing the process. The driven alloys concept offers a more rational framework to interpret the effect of the milling temperature. Other results are presented which demonstrate the possibility for grinding to realize low temperature solid state alloying which offers new promising ways to stabilize amorphous molecular solids. In a second part the effect of dehydration of a molecular hydrate is described. It is shown that the rate of the dehydration process is a driving force for this other type of mechanical non equilibrium transformation.

  13. Prediction of thermal cycling induced cracking in polymer matrix composites

    NASA Technical Reports Server (NTRS)

    Mcmanus, Hugh L.

    1993-01-01

    This report summarizes the work done in the period February 1993 through July 1993 on the 'Prediction of Thermal Cycling Induced Cracking In Polymer Matrix Composites' program. An oral presentation of this work was given to Langley personnel in September of 1993. This document was prepared for archival purposes. Progress studies have been performed on the effects of spatial variations in material strength. Qualitative agreement was found with observed patterns of crack distribution. These results were presented to NASA Langley personnel in November 1992. The analytical methodology developed by Prof. McManus in the summer of 1992 (under an ASEE fellowship) has been generalized. A method for predicting matrix cracking due to decreasing temperatures and/or thermal cycling in all plies of an arbitrary laminate has been implemented as a computer code. The code also predicts changes in properties due to the cracking. Experimental progressive cracking studies on a variety of laminates were carried out at Langley Research Center. Results were correlated to predictions using the new methods. Results were initially mixed. This motivated an exploration of the configuration of cracks within laminates. A crack configuration study was carried out by cutting and/or sanding specimens in order to examine the distribution of cracks within the specimens. These investigations were supplemented by dye-penetrant enhanced X-ray photographs. The behavior of thin plies was found to be different from the behavior of thicker plies (or ply groups) on which existing theories are based. Significant edge effects were also noted, which caused the traditional metric of microcracking (count of cracks on a polished edge) to be very inaccurate in some cases. With edge and configuration taken into account, rough agreement with predictions was achieved. All results to date were reviewed with NASA Langley personnel in September 1993.

  14. [Ascorbate-glutathione cycle enzymes activity in Zea mays leaves under salinity and treatment by adaptogenic compounds].

    PubMed

    Konturs'ka, O O; Palladina, T O

    2012-01-01

    The effect of different salinity levels and synthetic compounds treatments on ascorbate-glutathione cycle enzymes activity in maize leaves has been investigated. One-day seedlings exposition with 0.05 M NaCl increased ascorbate peroxidase activity, whereas 10-day exposition did not affect it. However the exposition with 0.1 M NaCl, which is extreme for maize, decreased ascorbate peroxidase activity in leaves during 10 days. On the other hand glutathione reductase activity in leaves increased under both salt concentrations. Seeds treatments with Methyure and Ivine increased ascorbate peroxidase activity in the leaves of seedlings under 0.1 M NaCl, but did not affect glutathione reductase activity as compared to the salt control. The results obtained have shown differences of ascorbate-glutathione cycle enzymes responses to salt exposition of seedlings and the effects of adaptogenic compounds on the ascorbate-glutathione cycle via ascorbate peroxidase activation. PMID:23387279

  15. Cycle-Induced Flow and Surfactant Transport in an Alveolus

    NASA Astrophysics Data System (ADS)

    Wei, H. H.

    2002-11-01

    The flow and transport in an alveolus are of fundamental importance to partial liquid ventilation, surfactant transport, pulmonary drug administration, cell-cell signaling pathways and gene therapy. We model the system in which an alveolus is partially filled with liquid in the presence of surfactants. Assuming a circular interface due to sufficiently strong surface tension, we can apply two-dimensional bipolar coordinates to describe the system. We then combine analytical and numerical techniques to solve the Stokes flow and the surfactant concentration. In the absence of surfactants, there is no steady streaming because of reversibility of the Stokes flow. The presence of surfactants however induces a non-trivial cycle-averaged surfactant concentration gradient along the interface that generates steady streaming. The steady streaming patterns (e.g., number of vortices) depend on the parameters, especially on the ratio of inspiration to expiration periods (I:E ratio). Either smaller or larger I:E ratio exhibits two primary vortices but the direction of primary vortices for small I:E is opposite to large I:E. Extension to soluble surfactants is also discussed. For sufficiently high surfactant bulk concentration, the surfactant transport is sorption-controlled and soluble surfactants diminish the size of steady vortices near the alveolar opening. For the estimated steady velocity u 10-5 cm/s, the corresponding Peclet number is 10-7/ D_m. Therefore, for Dm <= 10-7 cm^2/s, the convective transport dominates.

  16. Hantzsch Ester as a Photosensitizer for the Visible-Light-Induced Debromination of Vicinal Dibromo Compounds.

    PubMed

    Chen, Wenxin; Tao, Huachen; Huang, Wenhao; Wang, Guoqiang; Li, Shuhua; Cheng, Xu; Li, Guigen

    2016-07-01

    The debromination of vicinal dibromo compounds to generate alkenes usually requires harsh reaction conditions and the addition of catalysts. Just recently the visible-light-induced debromination of vicinal dibromo compounds emerged as a possible alternative to commonly used methods, but the substrate scope of this reaction is limited and a photocatalyst is necessary for the successful conversion of the starting compounds. A catalyst-free visible-light-induced debromination of vicinal dibromo compounds with a base-activated Hantzsch ester as photosensitizer is reported. The method has a wide substrate scope and a broad functional-group compatibility. PMID:27128783

  17. Two host-inducible genes of Rhizobium fredii and characterization of the inducing compound.

    PubMed Central

    Sadowsky, M J; Olson, E R; Foster, V E; Kosslak, R M; Verma, D P

    1988-01-01

    Random transcription fusions with Mu d1(Kan lac) generated three mutants in Rhizobium fredii (strain USDA 201) which showed induction of beta-galactosidase when grown in root exudate of the host plants Glycine max, Phaseolus vulgaris, and Vigna ungliculata. Two genes were isolated from a library of total plasmid DNA of one of the mutants, 3F1. These genes, present in tandem on a 4.2-kilobase HindIII fragment, appear in one copy each on the symbiotic plasmid and do not hybridize to the Rhizobium meliloti common nodulation region. They comprise two separate transcriptional units coding for about 450 and 950 nucleotides, both of which are transcribed in the same direction. The two open reading frames are separated by 586 base pairs, and the 5H regions of the two genes show a common sequence. No similarity was found with the promoter areas of Rhizobium trifolii, R. meliloti, or Bradyrhizobium japonicum nif genes and with any known nodulation genes. Regions homologous to both sequences were detected in EcoRI digests of genomic DNAs from B. japonicum USDA 110, USDA 122, and 61A76, but not in genomic DNA from R. trifolii, Rhizobium leguminosarum, or Rhizobium phaseoli. Mass spectrometry and nuclear magnetic resonance analysis indicated that the inducing compound has properties of 4',7-dihydroxyisoflavone, daidzein. These results suggest that, in addition to common nodulation genes, several other genes appear to be specifically induced by compounds in the root exudate of the host plants. Images PMID:2447061

  18. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility.

    PubMed

    Kirby, R Jason; Qi, Feng; Phatak, Sharangdhar; Smith, Layton H; Malany, Siobhan

    2016-08-15

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. PMID:27343406

  19. Synthesis, Anticancer Activity, Effect on Cell Cycle Profile, and Apoptosis-Inducing Ability of Novel Hexahydrocyclooctathieno[2,3-d]pyrimidine Derivatives.

    PubMed

    Kassab, Asmaa Elsayed; Gedawy, Ehab Mohamed; El-Malah, Afaf Ali; Abdelghany, Tamer Mohamed; Abdel-Bakky, Mohamed Sadek

    2016-01-01

    A novel series of hexahydrocyclooctathieno[2,3-d]pyrimidines was synthesized. Investigation of the anticancer activity of these derivatives revealed that compounds 2a and b showed broad-spectrum anticancer activity in nanomolar to micromolar concentrations. In particular, compound 2b showed a concentration required for 50% inhibition of cell growth (GI50) value of less than 1 µM against 20 cancer cell lines. Compounds 2a and b induced G2/M- and S-phase cell cycle arrest in human colon adenocarcinoma (HCT116) and human breast adenocarcinoma (MCF7) cell lines with a concomitant increase in the pre-G cell population in a time-dependent manner. Furthermore, compound 2b increased the nuclear expression of the proapoptotic protein cleaved caspase-3, indicating that apoptosis has an important role, at least in part, in the cancer cell death induced by the new compounds. PMID:27150481

  20. Molecular markers and cell cycle inhibitors show the importance of cell cycle progression in nematode-induced galls and syncytia.

    PubMed Central

    de Almeida Engler, J; De Vleesschauwer, V; Burssens, S; Celenza, J L; Inzé, D; Van Montagu, M; Engler, G; Gheysen, G

    1999-01-01

    Root knot and cyst nematodes induce large multinucleated cells, designated giant cells and syncytia, respectively, in plant roots. We have used molecular markers to study cell cycle progression in these specialized feeding cells. In situ hybridization with two cyclin-dependent kinases and two cyclins showed that these genes were induced very early in galls and syncytia and that the feeding cells progressed through the G2 phase. By using cell cycle blockers, DNA synthesis and progression through the G2 phase, or mitosis, were shown to be essential for gall and syncytium establishment. When mitosis was blocked, further gall development was arrested. This result demonstrates that cycles of endoreduplication or other methods of DNA amplification are insufficient to drive giant cell expansion. On the other hand, syncytium development was much less affected by a mitotic block; however, syncytium expansion was inhibited. PMID:10330466

  1. Momordica cochinchinensis Spreng. seed extract suppresses breast cancer growth by inducing cell cycle arrest and apoptosis.

    PubMed

    Zheng, Lei; Zhang, Yanmin; Liu, Yanping; Yang, Xiaoyan Ou; Zhan, Yingzhuan

    2015-10-01

    The herb Momordica cochinchinensis has been used for a variety of purposes, and been shown to have anti‑cancer properties. The present study assessed the potency and the underlying mechanisms of action of the ethyl acetate extract of seeds of Momordica cochinchinensis (ESMC2) on breast cancer cells. Therefore, the effects of ESMC2 on the cell viability, cell cycle and apoptosis of MDA‑MB‑231 cells were investigated. The results showed that ESMC2 exerted a marked growth inhibitory effect on the cells. Cell cycle arrest in G2 phase following treatment with ESMC2 was associated with a marked increase in the protein levels of cyclin B1, cyclin E and cyclin-dependent kinase 1 and a decrease in cyclin D1 expression. In addition, ESMC2 dose‑dependently induced cell apoptosis, which was mediated via upregulation of the apoptosis-associated proteins p53, B-cell lymphoma 2 (Bcl‑2)‑associated X protein, Bcl-2 homologous antagonist killer and Bcl-2-associated death promoter expression, as well as downregulation of nuclear factor kappa B, Bcl‑2 and myeloid cell leukemia‑1. Furthermore, the activation of extracellular signal-regulated kinase 1/2, p38, c-Jun N-terminal kinase (JNK) and Akt phosphorylation were decreased by ESMC2 in a dose‑dependent manner, indicating that ESMC2 exerted its effects via the mitogen-activated protein kinase/JNK pathway. Furthermore, nude mouse xenotransplant models were used to evaluate the tumor growth inhibitory effects of ESMC2. The possible chemical components of ESMC2 were analyzed by gas chromatography-mass spectrometry, and 12 compounds were detected from the major peaks based on the similarity index with entries of a compound database. The results of the present study may aid in the development of novel therapies for breast cancer. PMID:26252798

  2. 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF); antimicrobial compound with cell cycle arrest in nosocomial pathogens.

    PubMed

    Sung, Woo Sang; Jung, Hyun Jun; Park, Keunnam; Kim, Hyun Soo; Lee, In-Seon; Lee, Dong Gun

    2007-01-16

    2,5-Dimethyl-4-hydroxy-3(2H)-furanone (DMHF), an aroma compound found in a number of fruits and foods, has shown various biological properties in animal models, but its antimicrobial effect remains poorly understood. The current study investigated the antimicrobial effect of DMHF using human pathogenic microorganisms including clinically isolated antibiotics-resistant strains. The results indicated that DMHF exhibited broad spectrum antimicrobial activities in an energy-dependent manner without hemolytic effect on human erythrocytes. To confirm antifungal effect of DMHF, we investigated the effect on dimorphism of Candida albicans induced by FBS, which plays a key role for pathogenesis in host invasion. The result showed that DMHF exerted a potent antifungal activity on the serum-induced mycelia of C. albicans. To elucidate the physiological changes of the fungal cells induced by DMHF, cell cycle analysis was performed, and the results showed that DMHF arrested the cell cycle at the S and G2/M phase in yeast. Therefore, it could be expected that DMHF may have potential as an anti-infective agent in human microbial infections. PMID:17097685

  3. Reconstructing 40ky of N cycling from stable isotopes of plant compounds in a Siberian permafrost soil

    NASA Astrophysics Data System (ADS)

    Enders, S. K.; Houlton, B. Z.; Ohkouchi, N.; Wagner, D.; Ogawa, N. O.; Chikaraishi, Y.; Suga, H.

    2015-12-01

    Terrestrial nitrogen (N) cycling has an important dual role in regulating global climate, as N is both a limiting plant nutrient and a constituent of a potent greenhouse gas. Reconstructing past terrestrial N cycling is a valuable complement to experimental manipulation of complex climate-carbon-N interactions, but has been challenged by shortcomings of available proxies. We here examine 40ky of terrestrial N cycling on the landscape of northeast Siberia as recorded in N-isotopes of chlorophyll degradation products preserved in a permafrost soil core. This dataset gives insight into the response of the N cycle to concurrent changes in climate, plant community, and atmospheric pCO2 that accompany a cycle of glaciation. This study is the first application to temporal reconstruction of this compound-specific, soil-based proxy for an integrated foliar N isotope signal. We infer ~10 per mil swings in foliar N-isotope values at this site, pointing to the sensitivity of denitrification at high latitudes to changes in environmental conditions. We further observe the effect of increases in N-fixing species on stimulating N cycling as recorded by our proxy. We do not see an effect of progressive N limitation due to pre-anthropogenic increases in pCO2 accompanying deglaciation.

  4. High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage

    PubMed Central

    Gergely, Szabolcs; Hegedűs, Csaba; Lakatos, Petra; Kovács, Katalin; Gáspár, Renáta; Csont, Tamás; Virág, László

    2015-01-01

    Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury. PMID:26137186

  5. Radiation induced chemical changes of phenolic compounds in strawberries

    NASA Astrophysics Data System (ADS)

    Breitfellner, F.; Solar, S.; Sontag, G.

    2003-06-01

    In unirradiated strawberries four phenolic acids (gallic acid, p-coumaric acid, caffeic acid and 4-hydroxybenzoic acid), the flavonoids (+)-catechin, (-)-epicatechin and glycosides from kaempferol and quercetin were determined by reversed phase chromatography with diode array detection. Characteristic linear dose/concentration relationships were found for 4-hydroxybenzoic acid and two unidentified compounds. One of them may be usable as marker to prove an irradiation treatment.

  6. Roles of Autophagy Induced by Natural Compounds in Prostate Cancer

    PubMed Central

    Naponelli, V.; Bettuzzi, S.

    2015-01-01

    Autophagy is a homeostatic mechanism through which intracellular organelles and proteins are degraded and recycled in response to increased metabolic demand or stress. Autophagy dysfunction is often associated with many diseases, including cancer. Because of its role in tumorigenesis, autophagy can represent a new therapeutic target for cancer treatment. Prostate cancer (PCa) is one of the most common cancers in aged men. The evidence on alterations of autophagy related genes and/or protein levels in PCa cells suggests a potential implication of autophagy in PCa onset and progression. The use of natural compounds, characterized by low toxicity to normal tissue associated with specific anticancer effects at physiological levels in vivo, is receiving increasing attention for prevention and/or treatment of PCa. Understanding the mechanism of action of these compounds could be crucial for the development of new therapeutic or chemopreventive options. In this review we focus on the current evidence showing the capacity of natural compounds to exert their action through autophagy modulation in PCa cells. PMID:25821782

  7. Adenosine induces G2/M cell-cycle arrest by inhibiting cell mitosis progression.

    PubMed

    Jia, Kun-Zhi; Tang, Bo; Yu, Lu; Cheng, Wei; Zhang, Rong; Zhang, Jian-Fa; Hua, Zi-Chun

    2010-01-01

    Cellular adenosine accumulates under stress conditions. Few papers on adenosine are concerned with its function in the cell cycle. The cell cycle is the essential mechanism by which all living things reproduce and the target machinery when cells encounter stresses, so it is necessary to examine the relationship between adenosine and the cell cycle. In the present study, adenosine was found to induce G-2/M cell-cycle arrest. Furthermore, adenosine was found to modulate the expression of some important proteins in the cell cycle, such as cyclin B and p21, and to inhibit the transition of metaphase to anaphase in mitosis. PMID:19947935

  8. Quinones and Aromatic Chemical Compounds in Particulate Matter Induce Mitochondrial Dysfunction: Implications for Ultrafine Particle Toxicity

    PubMed Central

    Xia, Tian; Korge, Paavo; Weiss, James N.; Li, Ning; Venkatesen, M. Indira; Sioutas, Constantinos; Nel, Andre

    2004-01-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)–enriched aromatic fraction in O2•− generation, decrease of membrane potential (ΔΨm), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)–sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on ΔΨm at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in ΔΨm at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and ΔΨm are mediated by adsorbed chemicals rather than the particles themselves. PMID:15471724

  9. Metrological characterization of a cycle-ergometer to optimize the cycling induced by functional electrical stimulation on patients with stroke.

    PubMed

    Comolli, Lorenzo; Ferrante, Simona; Pedrocchi, Alessandra; Bocciolone, Marco; Ferrigno, Giancarlo; Molteni, Franco

    2010-05-01

    Functional electrical stimulation (FES) is a well established method in the rehabilitation of stroke patients. Indeed, a bilateral movement such as cycling induced by FES would be crucial for these patients who had an unilateral motor impairment and had to recover an equivalent use of limbs. The aim of this study was to develop a low-cost meteorologically qualified cycle-ergometer, optimized for patients with stroke. A commercial ergometer was instrumented with resistive strain gauges and was able to provide the torque produced at the right and left crank, independently. The developed system was integrated with a stimulator, obtaining a novel FES cycling device able to control in real-time the movement unbalance. A dynamic calibration of the sensors was performed and a total torque uncertainty was computed. The system was tested on a healthy subject and on a stroke patient. Results demonstrated that the proposed sensors could be successfully used during FES cycling sessions where the maximum torque produced is about 9Nm, an order of magnitude less than the torque produced during voluntary cycling. This FES cycling system will assist in future investigations on stroke rehabilitation by means of FES and in new exercise regimes designed specifically for patients with unilateral impairments. PMID:20171923

  10. Profiling the NIH Small Molecule Repository for Compounds That Generate H2O2 by Redox Cycling in Reducing Environments

    PubMed Central

    2010-01-01

    We have screened the Library of Pharmacologically Active Compounds (LOPAC) and the National Institutes of Health (NIH) Small Molecule Repository (SMR) libraries in a horseradish peroxidase–phenol red (HRP-PR) H2O2 detection assay to identify redox cycling compounds (RCCs) capable of generating H2O2 in buffers containing dithiothreitol (DTT). Two RCCs were identified in the LOPAC set, the ortho-naphthoquinone β-lapachone and the para-naphthoquinone NSC 95397. Thirty-seven (0.02%) concentration-dependent RCCs were identified from 195,826 compounds in the NIH SMR library; 3 singleton structures, 9 ortho-quinones, 2 para-quinones, 4 pyrimidotriazinediones, 15 arylsulfonamides, 2 nitrothiophene-2-carboxylates, and 2 tolyl hydrazides. Sixty percent of the ortho-quinones and 80% of the pyrimidotriazinediones in the library were confirmed as RCCs. In contrast, only 3.9% of the para-quinones were confirmed as RCCs. Fifteen of the 251 arylsulfonamides in the library were confirmed as RCCs, and since we screened 17,868 compounds with a sulfonamide functional group we conclude that the redox cycling activity of the arylsulfonamide RCCs is due to peripheral reactive enone, aromatic, or heterocyclic functions. Cross-target queries of the University of Pittsburgh Drug Discovery Institute (UPDDI) and PubChem databases revealed that the RCCs exhibited promiscuous bioactivity profiles and have populated both screening databases with significantly higher numbers of active flags than non-RCCs. RCCs were promiscuously active against protein targets known to be susceptible to oxidation, but were also active in cell growth inhibition assays, and against other targets thought to be insensitive to oxidation. Profiling compound libraries or the hits from screening campaigns in the HRP-PR H2O2 detection assay significantly reduce the timelines and resources required to identify and eliminate promiscuous nuisance RCCs from the candidates for lead optimization. PMID:20070233

  11. TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling

    SciTech Connect

    Ding, Li; Huang, Yong; Du, Qian; Dong, Feng; Zhao, Xiaomin; Zhang, Wenlong; Xu, Xingang; Tong, Dewen

    2014-03-07

    Highlights: • TGEV N protein reduces cell viability by inducing cell cycle arrest and apoptosis. • TGEV N protein induces cell cycle arrest and apoptosis by regulating p53 signaling. • TGEV N protein plays important roles in TGEV-induced cell cycle arrest and apoptosis. - Abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressed cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence.

  12. Temperature Cycles Induce Early Maturation in Channel Catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major impediment in improvement of channel catfish by selective breeding is that a high percent of fish do not spawn until the third year. The conditions that lead to sexual maturation in fish have not been established. Size, nutritional state and number of seasonal cycles have all been suggeste...

  13. A novel cromakalim analogue induces cell cycle arrest and apoptosis in human cervical carcinoma HeLa cells through the caspase- and mitochondria-dependent pathway.

    PubMed

    Zhang, Xin; Zhao, Jing; Kang, Saeromi; Yi, Myeongjin; You, Song; Shin, Dong-Soo; Kim, Dong-Kyoo

    2011-12-01

    In the present study, a series of seven synthetic croma-kalim analogues were prepared and evaluated for cytotoxic effect on human cervical carcinoma HeLa cells using WST-8 assay. A preliminary screening of these cromakalim analogues showed that 1-[(3S,4R)-4-(2-ethoxy-4-methyl-1H-pyrrol-1-yl)-3-hydroxy- 2,2-dimethylchroman-6-yl-3-phenylurea (compound 6) had the highest cytotoxic effect (IC50 of 138 µM) and significantly inhibited HeLa cell proliferation after 36 h. In an effort to understand the cytotoxic mechanism of compound 6, we examined its effect on apoptosis and cell cycle distribution. Our results showed that compound 6 induced marked changes in apoptotic morphology and significantly increased early apoptosis of HeLa cells after 48 h by using Annexin V-FITC/PI dual staining assay. This apoptotic induction was associated with an increase in Bax expression, a decrease in Bcl-2 expression, release of cytochrome c and subsequent activation of caspase-9 and -3, which indicated that compound 6 induced apoptosis via caspase- and mitochondria-dependent pathway. By DNA content analysis and [3H]thymidine incorporation assay, compound 6 was found to induce an increase in the number of cells in G1 phase, accompanied by a decrease in the S phase to prevent DNA synthesis after 24 h of treatment. In addition, compound 6 caused significant DNA damage, as detected by the alkaline comet assay. Taken together, the data demonstrate that compound 6 induces apoptosis in HeLa cells through caspase- and mitochondria-dependent pathway and this apoptotic effect is associated with cell cycle arrest and DNA damage. These findings provide further understanding of the molecular mechanisms of compound 6 in cervical cancer. PMID:21833470

  14. Occurrence and distribution of psychoactive compounds and their metabolites in the urban water cycle of Berlin (Germany).

    PubMed

    Hass, Ulrike; Duennbier, Uwe; Massmann, Gudrun

    2012-11-15

    The occurrence and distribution of six psychoactive compounds (primidone, phenobarbital, oxazepam, diazepam, meprobamate, and pyrithyldione) and a metabolite of primidone (phenylethylmalonamide) were investigated in wastewater treatment plant (WWTP) effluents, surface water, groundwater of a bank filtration site, raw and final drinking water, and in groundwater affected by former sewage irrigation. Primidone and its metabolite phenylethylmalonamide were found to be ubiquitous in environmental water samples in Berlin. Maximum concentrations of 0.87 and 0.42 μg/L, respectively, were encountered in WWTP effluents. Both compounds are apparently not removed when passaging through the different compartments of the water cycle and concentrations are only reduced by dilution. Phenobarbital was present at nearly every stage of the Berlin water cycle with the exception of raw and final drinking water. The highest concentrations of phenobarbital (up to 0.96 μg/L) were measured in groundwater influenced by former sewage irrigation. Oxazepam was only present in WWTP effluents and surface waters (up to 0.18 μg/L), while diazepam was not detected in any matrix. Due to their withdrawal from the German market years ago, the pharmaceuticals meprobamate and pyrithyldione were only found in sewage farm groundwater (up to 0.50 and 0.04 μg/L, respectively) and, in case of meprobamate, also in decade old bank filtrate (0.03 μg/L). Our results indicate a high persistence of some of the investigated compounds in the aquatic system. As a consequence, these pollutants may potentially reach drinking water resources via bank filtration if present in WWTP effluents and/or surface waters in partly closed water cycles such as Berlin's. PMID:22967903

  15. Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines

    PubMed Central

    Esmaeelian, Babak; Benkendorff, Kirsten; Johnston, Martin R.; Abbott, Catherine A.

    2013-01-01

    Dicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninone and 6-bromoisatin as the most active against colon cancer cells HT29 and Caco-2. Liquid chromatography coupled with mass spectrometry (LCMS) and 1H NMR were used to characterize the purity and chemical composition of the isolated compounds. An MTT assay was used to determine effects on cell viability. Necrosis and apoptosis induction using caspase/LDH assay and flow cytometry (PI/Annexin-V) and cell cycle analysis were also investigated. Our results show that semi-purified 6-bromoisatin had the highest anti-cancer activity by inhibiting cell viability (IC50 = ~100 µM) and increasing caspase 3/7 activity in both of the cell lines at low concentration. The fraction containing 6-bromoisatin induced 77.6% apoptosis and arrested 25.7% of the cells in G2/M phase of cell cycle in HT29 cells. Tyrindoleninone was less potent but significantly decreased the viability of HT29 cells at IC50 = 390 µM and induced apoptosis at 195 µM by increasing caspase 3/7 activity in these cells. This research will facilitate the development of these molluscan natural products as novel complementary medicines for colorectal cancer. PMID:24152558

  16. Radioactive-induced tumors by phosphorus-32 as colloidal compound

    SciTech Connect

    Ubios, A.M.; Silberman, F.S.; Cabrini, R.L.

    1983-05-01

    Chromic colloidal phosphate labeled with 32P, which has been proposed for the treatment of several articular diseases, was injected intra-articularly in the knee joint of adult Wistar rats. After a 270 days minimum latent period, tumors began to appear in the injected zone, to a 70% frequency. Ten lung metastases were detected. In five cases, squamous cell carcinomas were induced in the injected area. The relevance of a sound evaluation of the risk involved in treatments with radioactive isotopes, is discussed.

  17. Emergy Evaluations of the Global Biogeochemical Cycles of Six Biologically Active Elements and Two Compounds

    EPA Science Inventory

    Estimates of the emergy carried by the flows of biologically active elements (BAE) and compounds are needed to accurately evaluate the near and far field effects of anthropogenic wastes. The transformities and specific emergies of these elements and of their different chemical sp...

  18. Computer simulation of the heavy-duty turbo-compounded diesel cycle for studies of engine efficiency and performance

    NASA Technical Reports Server (NTRS)

    Assanis, D. N.; Ekchian, J. A.; Heywood, J. B.; Replogle, K. K.

    1984-01-01

    Reductions in heat loss at appropriate points in the diesel engine which result in substantially increased exhaust enthalpy were shown. The concepts for this increased enthalpy are the turbocharged, turbocompounded diesel engine cycle. A computer simulation of the heavy duty turbocharged turbo-compounded diesel engine system was undertaken. This allows the definition of the tradeoffs which are associated with the introduction of ceramic materials in various parts of the total engine system, and the study of system optimization. The basic assumptions and the mathematical relationships used in the simulation of the model engine are described.

  19. Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs

    PubMed Central

    Chang, Mei-Yin; Shieh, Den-En; Chen, Chung-Chi; Yeh, Ching-Sheng; Dong, Huei-Ping

    2015-01-01

    Plantaginaceae, a popular traditional Chinese medicine, has long been used for treating various diseases from common cold to cancer. Linalool is one of the biologically active compounds that can be isolated from Plantaginaceae. Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible tumor cells. However, the signaling pathway for apoptosis remains undefined. In this study, the cytotoxic effect of linalool on human cancer cell lines was investigated. Water-soluble tetrazolium salts (WST-1) based colorimetric cellular cytotoxicity assay, was used to test the cytotoxic ability of linalool against U937 and HeLa cells, and flow cytometry (FCM) and genechip analysis were used to investigate the possible mechanism of apoptosis. These results demonstrated that linalool exhibited a good cytotoxic effect on U937 and HeLa cells, with the IC50 value of 2.59 and 11.02 μM, respectively, compared with 5-FU with values of 4.86 and 12.31 μM, respectively. After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby these cells were arrested at the G0/G1 phase. Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. Therefore, this study verified that linalool can arrest the cell cycle of U937 cells at the G0/G1 phase and can arrest the cell cycle of HeLa cells at the G2/M phase. Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p53, p21, p27, p16, and p18, as well as the non-expression of cyclin-dependent kinases (CDKs) activity. PMID:26703569

  20. Drought-induced Changes in Dryland Soil Biogeochemical Cycles

    NASA Astrophysics Data System (ADS)

    Belnap, J.; Darrouzet-Nardi, A.; Duniway, M.; Ferrenberg, S.; Hoover, D. L.; Reed, S.

    2015-12-01

    Approximately 41% of Earth´s terrestrial surface consists of drylands and they are an important biome on all continents. Although dryland biota would be expected to be drought adapted, they can be surprisingly vulnerable to extended dry periods with subsequent consequences for biogeochemical cycles. Biological soil crusts, constituting up to 70% of the living cover in these regions, are important in these cycles. They fix both N and C, providing a significant percentage of regional and global inputs. However, extended drought reduces both types of inputs, as biocrusts are only metabolically active when wet, yet losses continue even when soils are dry. In addition, extended droughts can result in their mortality. The amount of net soil C exchange of biocrusted soils is controversial, but in SE Utah, soil C uptake only occurred when only when soils were wet. As soils are infrequently wet, annual balances were negative during the 2 year study and with future extended droughts or increased temperatures that reduce soil moisture, these losses will become even greater. As with C, N fixation also requires biocrusts be wet and thus inputs decline with extended drought or higher temperatures that both reduce input and result in lichen and cyanobacterial mortality. And similarly, N losses continue even when soils are dry. Loss of biocrust mosses can profoundly alter N cycles. Desert plants are also affected by drought: in plots where experimental drought was imposed, plants had lower photosynthetic rates and higher leaf C:N, which will likely affect productivity and decomposition rates and thus have further impacts on soil biogeochemical cycles.

  1. UV-induced changes in cell cycle and gene expression within rabbit lens epithelial cells

    SciTech Connect

    Sidjanin, D.; Grdina, D.; Woloschak, G.E.

    1994-11-01

    Damage to lens epithelial cells is a probable initiation process in cataract formation induced by ultraviolet radiation. These experiments investigated the ability of 254 nm radiation on cell cycle progression and gene expression in rabbit lens epithelial cell line N/N1003A. No changes in expression of c-fos, c-jun, alpha- tubulin, or vimentin was observed following UV exposure. Using flow cytometry, an accumulation of cells in G1/S phase of the cell cycle 1 hr following exposure. The observed changes in gene expression, especially the decreased histone transcripts reported here may play a role in UV induced inhibition of cell cycle progression.

  2. Computation Molecular Kinetics Model of HZE Induced Cell Cycle Arrest

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Ren, Lei

    2004-01-01

    Cell culture models play an important role in understanding the biological effectiveness of space radiation. High energy and charge (HZE) ions produce prolonged cell cycle arrests at the G1/S and G2/M transition points in the cell cycle. A detailed description of these phenomena is needed to integrate knowledge of the expression of DNA damage in surviving cells, including the determination of relative effectiveness factors between different types of radiation that produce differential types of DNA damage and arrest durations. We have developed a hierarchical kinetics model that tracks the distribution of cells in various cell phase compartments (early G1, late G1, S, G2, and M), however with transition rates that are controlled by rate-limiting steps in the kinetics of cyclin-cdk's interactions with their families of transcription factors and inhibitor molecules. The coupling of damaged DNA molecules to the downstream cyclin-cdk inhibitors is achieved through a description of the DNA-PK and ATM signaling pathways. For HZE irradiations we describe preliminary results, which introduce simulation of the stochastic nature of the number of direct particle traversals per cell in the modulation of cyclin-cdk and cell cycle population kinetics. Comparison of the model to data for fibroblast cells irradiated photons or HZE ions are described.

  3. Competition between the compound and the pre-compound emission processes in α-induced reactions at near astrophysical energy to well above it

    NASA Astrophysics Data System (ADS)

    Sharma, Manoj Kumar; Sharma, Vijay Raj; Yadav, Abhiskek; Singh, Pushpendra P.; Singh, B. P.; Prasad, R.

    2016-04-01

    The study of pre-compound emission in α-induced reactions, particularly at the low incident energies, is of considerable interest as the pre-compound emission is more likely to occur at higher energies. With a view to study the competition between the compound and the pre-compound emission processes in α-induced reactions at different energies and with different targets, a systematics for neutron emission channels in targets 51V, 55Mn, 93Nb, 121, 123Sb and 141Pr at energy ranging from astrophysical interest to well above it, has been developed. The off-line γ-ray-spectrometry based activation technique has been adopted to measure the excitation functions. The experimental excitation functions have been analysed within the framework of the compound nucleus mechanism based on the Weisskopf-Ewing model and the pre-compound emission calculations based on the geometry dependent hybrid model. The analysis of the data shows that experimental excitation functions could be reproduced only when the pre-compound emission, simulated theoretically, is taken into account. The strength of pre-compound emission process for each system has been obtained by deducing the pre-compound fraction. Analysis of data indicates that in α-induced reactions, the pre-compound emission process plays an important role, particularly at the low incident energies, where the pure compound nucleus process is likely to dominate.

  4. The mechanism of alcoholic beverage induced superconductivity in Fe-chalcogenide compounds

    NASA Astrophysics Data System (ADS)

    Deguchi, Keita; Demura, Satoshi; Okazaki, Hiroyuki; Denholme, Saleem; Fujioka, Masaya; Ozaki, Toshinori; Yamaguchi, Takahide; Takeya, Hiroyuki; Takano, Yoshihiko

    2013-03-01

    We have clarified the mechanism of alcoholic beverage induced superconductivity in Fe-chalcogenide compounds. Previously we reported that the bulk superconductivity in Fe-based compounds Fe(Te, Se) and Fe(Te, S) is achieved by heating in alcoholic beverages. However, the exact mechanism of how they act to enhance the superconductivity in the compounds remains unsolved. To understand the effect of alcoholic beverage treatment, we investigated the mechanism using a technology of metabolomic analysis. We found that weak acid in alcoholic beverages has the ability to deintercalate the excess Fe, which is not in favor of superconductivity. In this presentation, we will discuss the systematic mechanism to induce superconductivity in Fe-chalcogenide compounds.

  5. Glutathione prevents ethanol induced gastric mucosal damage and depletion of sulfhydryl compounds in humans.

    PubMed Central

    Loguercio, C; Taranto, D; Beneduce, F; del Vecchio Blanco, C; de Vincentiis, A; Nardi, G; Romano, M

    1993-01-01

    Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione significantly decreased the extent of ethanol induced macroscopic injury to the mucosa of the gastric body and antrum. Glutathione's protective effect is associated with appreciable inhibition of ethanol induced depletion of gastric sulfhydryl compounds. This is the first report of protection against ethanol induced gastric mucosal damage by a sulfhydryl containing agent in humans. PMID:8432465

  6. The Protective Role of Phenolic Compounds Against Doxorubicin-induced Cardiotoxicity: A Comprehensive Review.

    PubMed

    Razavi-Azarkhiavi, Kamal; Iranshahy, Milad; Sahebkar, Amirhossein; Shirani, Kobra; Karimi, Gholamreza

    2016-01-01

    Although doxorubicin (DOX) is among the most widely used anticancer agents, its clinical application is hampered owing to its cardiotoxicity. Adjuvant therapy with an antioxidant has been suggested as a promising strategy to reduce DOX-induced adverse effects. In this context, many phenolic compounds have been reported to protect against DOX-induced cardiotoxicity. The cardioprotective effects of phenolic compounds are exerted via multiple mechanisms including inhibition of reactive oxygen species generation, apoptosis, NF-κB, p53, mitochondrial dysfunction, and DNA damage. In this review, we present a summary of the in vitro, in vivo, and clinical findings on the protective mechanisms of phenolic compounds against DOX-induced cardiotoxicity. PMID:27341037

  7. Induction of cell cycle arrest in prostate cancer cells by the dietary compound isoliquiritigenin.

    PubMed

    Lee, Yeo Myeong; Lim, Do Young; Choi, Hyun Ju; Jung, Jae In; Chung, Won-Yoon; Park, Jung Han Yoon

    2009-02-01

    Isoliquiritigenin (ISL), a flavonoid chalcone that is present in licorice, shallot, and bean sprouts, is known to have antitumorigenic activities. The present study examined whether ISL alters prostate cancer cell cycle progression. DU145 human and MatLyLu (MLL) rat prostate cancer cells were cultured with various concentrations of ISL. In both DU145 and MLL cells treated with ISL, the percentage of cells in the G1 phase increased, and the incorporation of [(3)H]thymidine decreased. ISL decreased the protein levels of cyclin D1, cyclin E, and cyclin-dependent kinase (CDK) 4, whereas cyclin A and CDK2 expressions were unaltered in cells treated with ISL. The expression of the CDK inhibitor p27(KIP1) was increased in cells treated with 20 micromol/L ISL. In addition, treatment of cells with 20 micromol/L ISL for 24 hours led to G2/M cell cycle arrest. Cell division control (CDC) 2 protein levels remained unchanged. The protein levels of phospho-CDC2 (Tyr15) and cyclin B1 were increased, and the CDC25C level was decreased by ISL dose-dependently. We demonstrate that ISL promotes cell cycle arrest in DU145 and MLL cells, thereby providing insights into the mechanisms underlying its antitumorigenic activities. PMID:19298190

  8. Deuterium enrichment by selective photo-induced dissociation of an organic carbonyl compound

    DOEpatents

    Marling, John B.

    1981-01-01

    A method for producing a deuterium enriched material by photoinduced dissociation which uses as the working material a gas phase photolytically dissociable organic carbonyl compound containing at least one hydrogen atom bonded to an atom which is adjacent to a carbonyl group and consisting of molecules wherein said hydrogen atom is present as deuterium and molecules wherein said hydrogen atom is present as another isotope of hydrogen. The organic carbonyl compound is subjected to intense infrared radiation at a preselected wavelength to selectively excite and thereby induce dissociation of the deuterium containing species to yield a deuterium enriched stable molecular product. Undissociated carbonyl compound, depleted in deuterium, is preferably redeuterated for reuse.

  9. Climatically induced sedimentary cycles in Pliocene deep-water carbonates

    SciTech Connect

    Gardulski, A.F. )

    1991-03-01

    Two DSDP sites (86 and 94) on the Campeche ramp in the southern Gulf of Mexico penetrated more than 100 m of Pliocene pelagic ooze. The ooze is primarily carbonate, with a much smaller volcanic ash component than occurs in some Pleistocene sediments at these sites. Cores recovered from these holes display variations in carbonate mineralogy as well as total carbonate and sand abundances that are correlated with the oxygen isotope stratigraphy. Diagenetic loss of Mg-calcite is complete by the base of the Pleistocene, but aragonite, especially high-Sr aragonite forming algal needles that were transported off the shelf to the slope, persists through upper Pliocene cores. Variations in oxygen isotope ratios in planktonic foraminifera occur throughout the Pliocene, although the amplitude of those cycles is smaller than for the Pleistocene, with its more dramatic glacial-interglacial contrasts. As in overlying Pleistocene slope sediments, cooler intervals correspond with greater abundances of aragonite in the upper Pliocene section, reflecting a shift of the shallow, productive shelf seaward across the ramp surface during times of relatively low sea level. However, the aragonite abundances in the Pliocene are reduced on average compared to the Pleistocene. This difference is due in part to diagenetic loss, but also it likely reflects the overall higher sea level that apparently characterized Pliocene oceans, trapping more algal aragonite landward. Although sea level and climatic fluctuations were indeed less extreme in the Pliocene, they were still sufficient to generate sedimentary cycles in deep-water carbonates.

  10. The menstrual cycle and susceptibility to coriolis-induced sickness.

    PubMed

    Cheung, B; Heskin, R; Hofer, K; Gagnon, M

    2001-01-01

    Survey studies on motion sickness susceptibility suggest that females tend to report greater severity in illness and higher incidence of vomiting than males. Menstruation is said to be a contributing factor. A recent study suggested that females were least susceptible to seasickness during ovulation in a "round the world" yacht race. Sixteen subjects (18-36 years old) were exposed to Coriolis cross-coupling stimulation in the laboratory. They were tested once during permenstruation (Day 1-5), ovulation (Day 12-15) and premenstruation (Day 24-28), based on a normalized 28-day cycle, in a randomised design. Physiological measurements of motion sickness included forearm and calf cutaneous blood flow. Subjective evaluation of sickness symptoms was based on Graybiel's diagnostic criteria and Golding's rating method. Our results indicated that under controlled laboratory conditions, different phases of the menstrual cycle appear to have no influence on subjective symptoms of motion sickness or on cutaneous blood flow increase in the forearm and calf. The lack of commonality between the types and levels of hormones that are released during motion sickness and those that are involved in different menstrual phases appears to support our findings. PMID:11847456

  11. An analysis of a highly compounded two-stroke-cycle compression-ignition engine

    NASA Technical Reports Server (NTRS)

    Tauschek, Max J; Sather, Bernard I; Biermann, Arnold E

    1949-01-01

    Presents an analysis of a compound engine operating with manifold pressures ranging from 60 to 110 lb/sq in. absolute. The effects of engine limits (peak cylinder pressure and turbine-inlet temperature) and component efficiency are discussed. A range analysis is used to evaluate the merit of the engine. The analysis indicates that specific-fuel-consumption values of 0.32 lb/bhp-hr and specific weights of 0.8 lb/bhp are obtainable at high manifold pressures.

  12. Starspot-Induced Radial Velocity Jitter During a Stellar Cycle

    NASA Astrophysics Data System (ADS)

    Korhonen, Heidi; Andersen, Jan Marie; Järvinen, Silva

    2014-04-01

    Late-type stars exhibit cool regions on their surface, the stellar equivalent of sunspots. These dark starspots can also mimic the radial velocity variations caused by orbiting planets, making it at times difficult to distinguish between planets and activity signatures. The amount of spots on the Sun and other cool stars changes cyclically during an activity cycle, which has length varying from about a year to longer than the solar 11 years. In this work we investigate the influence of varying amount of starspots on the sparsely sampled radial velocity observations - which are the norm in the radial velocity studies searching for exoplanets on wide orbits. We study two simulated cases: one with a random spot configuration, and one where the spot occurrence is concentrated. In addition we use Doppler images of young solar analogue V889 Her as a high activity case.

  13. Bromine isotope analysis - a tool for investigating biogeochemical cycle of bromine-containing organic and inorganic compounds in the environment

    NASA Astrophysics Data System (ADS)

    Gelman, F.; Bernstein, A.; Levin, E.; Ronen, Z.; Halicz, L.

    2012-04-01

    Bromine naturally occurs mainly in the form of bromide and is usually considered as a conservative tracer in the groundwater system. However, nowadays many synthetically produced organobromine compounds are introduced into the environment by humans. Due to a possible toxic effect of these compounds, investigation of their fate in the nature is of the utmost importance. In this sense, examination of isotopic composition of inorganic and organic bromine may serve as a powerful tool for understanding Br geochemical cycle. Due to a relatively small mass difference between the isotopes 81Br and 79Br, bromine isotope fractionation originating from biotic and abiotic processes is expected to be in the range of several permille. Therefore, a highly precise technique for the bromine isotope ratio analysis is required. This work presents a new methodology for the precise determination of bromine isotope ratio in inorganic bromides and individual organic compounds by MC-ICPMS. Attained external precision (2σ) up to 0.1‰ allowed employment of the developed technique for determination of the bromine isotope composition in organic and inorganic bromides and Br KIE in biogeochemical processes.

  14. Metabolic changes induced by sustained exhaustive cycling and diet manipulation.

    PubMed

    Brouns, F; Saris, W H; Beckers, E; Adlercreutz, H; van der Vusse, G J; Keizer, H A; Kuipers, H; Menheere, P; Wagenmakers, A J; ten Hoor, F

    1989-05-01

    Thirteen highly trained subjects were studied concerning the effect of consuming a normal carbohydrate-rich diet (N) on energy exchange, substrate metabolism, and performance. Six of these subjects performed the same protocol receiving N supplemented with a high-maltodextrin, low-fructose beverage (Mf). The studies were performed in random order. The subjects performed 2 days of sustained exhausting cycling, preceded and followed by a standardized resting day, in a respiration chamber, allowing continuous gas analysis, weighed food and fluid intake procedures, collection of excretes, and drawing of blood samples at 7:00 AM, 12:00 AM (halfway exercise) and 3:00 PM at exhaustion. Muscle biopsies were taken prior to, 45 min after, and 24 h after exercise (energy expenditure 25.2-26.6 MJ.day-1). The results showed that while consuming a normal diet, the cyclists developed a negative energy balance (-9 MJ.day-1) and regulated their hormone levels in such a way that fat oxidation and protein breakdown were increased and CHO oxidation became depressed. When supplemented with Mf, the subjects showed increased blood glucose, insulin and decreased glucagon levels. Fat metabolism was significantly depressed as indicated by the levels of blood fatty acids, glycerol, and ketones. A significant glycogen sparing, as well as supercompensation within 24 h of recovery, was observed after Mf supplementation. The normal CHO-rich diet, available ad libitum, was insufficient to fully restore glycogen within 24 h. The changes in substrate availability and glycogen depletion were accompanied by a significant performance improvement, 126% when cycling a final 90% Wmax bout, when supplemented with Mf compared with N. PMID:2663743

  15. Triptolide Abrogates Growth of Colon Cancer and Induces Cell Cycle Arrest by Inhibiting Transcriptional Activation of E2F

    PubMed Central

    Chugh, Rohit; Skube, Steven J; Majumder, Kaustav; Banerjee, Sulagna; Sangwan, Veena; Li, Lihua; Dawra, Rajinder; Subramanian, Subbaya; Saluja, Ashok; Dudeja, Vikas

    2016-01-01

    Background Despite significant progress in diagnostics and therapeutics, over fifty thousand patients die from colorectal cancer annually. Hence there is urgent need for new lines of treatment. Triptolide, a natural compound isolated from the Chinese herb Tripterygium wilfordii, is effective against multiple cancers. We have synthesized a water soluble analog of triptolide, named Minnelide, which is currently in phase I trial against pancreatic cancer. The aims of the current study were to evaluate whether triptolide/Minnelide is effective against colorectal cancer and to elucidate the mechanism by which triptolide induces cell death in colorectal cancer. Methods Efficacy of Minnelide was evaluated in subcutaneous xenograft and liver metastasis model of colorectal cancer. For mechanistic studies colon cancer cell lines HCT116 and HT29 were treated with triptolide and the effect on viability, caspase activation, annexin positivity, lactate dehydrogenase(LDH) release and cell cycle progression was evaluated. Effect of triptolide on E2F transcriptional activity, mRNA levels of E2F dependent genes, E2F1-Rb binding and proteins levels of regulator of G1-S transition was also measured. DNA binding of E2F1 was evaluated by chromatin immunoprecipitation assay. Results Triptolide decreased colon cancer cell viability in a dose- and time-dependent fashion. Minnelide markedly inhibited the growth of colon cancer in the xenograft and liver metastasis model of colon cancer and more than doubles the median survival of animals with liver metastases from colon cancer. Mechanistically we demonstrate that at low concentrations, triptolide induces apoptotic cell death but at higher concentrations it induces cell cycle arrest. Our data suggest that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Our data also show that triptolide downregulates E2F activity by potentially modulating events downstream of DNA binding. Conclusion

  16. Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F.

    PubMed

    Oliveira, Amanda R; Beyer, Georg; Chugh, Rohit; Skube, Steven J; Majumder, Kaustav; Banerjee, Sulagna; Sangwan, Veena; Li, Lihua; Dawra, Rajinder K; Subramanian, Subbaya; Saluja, Ashok K; Dudeja, Vikas

    2015-06-01

    Despite significant progress in diagnostics and therapeutics, over 50 thousand patients die from colorectal cancer annually. Hence, there is urgent need for new lines of treatment. Triptolide, a natural compound isolated from the Chinese herb Tripterygium wilfordii, is effective against multiple cancers. We have synthesized a water soluble analog of triptolide, named Minnelide, which is currently in phase I trial against pancreatic cancer. The aims of the current study were to evaluate whether triptolide/Minnelide is effective against colorectal cancer and to elucidate the mechanism by which triptolide induces cell death in colorectal cancer. Efficacy of Minnelide was evaluated in subcutaneous xenograft and liver metastasis model of colorectal cancer. For mechanistic studies, colon cancer cell lines HCT116 and HT29 were treated with triptolide and the effect on viability, caspase activation, annexin positivity, lactate dehydrogenase release, and cell cycle progression was evaluated. Effect of triptolide on E2F transcriptional activity, mRNA levels of E2F-dependent genes, E2F1- retinoblastoma protein (Rb) binding, and proteins levels of regulator of G1-S transition was also measured. DNA binding of E2F1 was evaluated by chromatin immunoprecipitation assay. Triptolide decreased colon cancer cell viability in a dose- and time-dependent fashion. Minnelide markedly inhibited the growth of colon cancer in the xenograft and liver metastasis model of colon cancer and more than doubles the median survival of animals with liver metastases from colon cancer. Mechanistically, we demonstrate that at low concentrations triptolide induces apoptotic cell death but at higher concentrations it induces cell cycle arrest. Our data suggest that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Our data also show that triptolide downregulates E2F activity by potentially modulating events downstream of DNA binding. Therefore, we conclude

  17. In vivo pharmacological evaluation of compound 48/80-induced airways oedema by MRI

    PubMed Central

    Karmouty-Quintana, H; Blé, F-X; Cannet, C; Zurbruegg, S; Fozard, J R; Page, C P; Beckmann, N

    2008-01-01

    Background and purpose: Allergen-induced airways oedema in actively sensitized rats has been studied earlier by magnetic resonance imaging (MRI). We used MRI to follow the consequences of non-immunological mast cell activation induced by compound 48/80 in the rat lungs in vivo. Experimental approach: Male naïve rats were scanned by MRI prior to and at several time points following intratracheal administration of the mast cell secretagogue, compound 48/80. The effects of a range of drugs on the response induced by compound 48/80 were studied. Key results: Strong fluid signals were detected by MRI in the lungs at 24 h after compound 48/80, correlating with increased protein concentration and inflammatory cell infiltration in bronchoalveolar lavage, and with perivascular oedema observed histologically. Pharmacological intervention demonstrated that the increase in MRI signal volume induced by compound 48/80 24 h after challenge was blocked by disodium cromoglycate and the glucocorticoid, budesonide. Pretreatment with wortmannin, capsazepine, DNK333 (a dual neurokinin (NK) 1 and NK2 antagonist) or the anti-allergy drug CGS8515, but not indomethacin, resulted in partial inhibition. Conclusions and implications: Compound 48/80 induced a complex inflammatory reaction which did not solely involve mast cell degranulation but also activation of sensory nerves and was qualitatively similar to allergen challenge. Changes observed by MRI correlated with decreases in protein concentration in BAL fluid. However, the magnitude of the changes detected was greater using MRI. Our results demonstrate that MRI is a sensitive and efficient tool to assess the effects of drugs on lung inflammation. PMID:18469845

  18. Martian induced magnetosphere variations with solar activity cycle

    NASA Astrophysics Data System (ADS)

    Fedorov, Andrey; Ronan, Modolo; Jarninen, Riku; Mazelle, Christian; Barabash, Stas

    2014-05-01

    During the last 6 years of ESA Mars Express mission we have accumulated plasma data taken inside and around the Martian induced magnetosphere corresponding to the increasing branch of solar activity. This data allows to make an enhanced study of the magnetosphere variations as a response of the solar activity level. Since Mars Express has no onboard magnetometer, we used the hybrid models of the Martian plasma environment to get a proper frame to make an adequate statistics of the magnetospheric response. In this paper we present a spatial distribution of the planetary plasma in the planetary wake as well as the ionsospheric escape as a function of the solar activity.

  19. Seasonal cycles of biogenic volatile organic compound fluxes and concentrations in a California citrus orchard

    NASA Astrophysics Data System (ADS)

    Fares, S.; Park, J.-H.; Gentner, D. R.; Weber, R.; Ormeño, E.; Karlik, J.; Goldstein, A. H.

    2012-07-01

    Orange trees are widely cultivated in Mediterranean climatic regions where they are an important agricultural crop. Citrus have been characterized as emitters of volatile organic compounds (VOC) in chamber studies under controlled environmental conditions, but an extensive characterization at field scale has never been performed using modern measurement methods, and is particularly needed considering the complex interactions between the orchards and the polluted atmosphere in which Citrus is often cultivated. For one year, in a Valencia orange orchard in Exeter, California, we measured fluxes using PTRMS (Proton Transfer Reaction Mass Spectrometer) and eddy covariance for the most abundant VOC typically emitted from citrus vegetation: methanol, acetone, and isoprenoids. Concentration gradients of additional oxygenated and aromatic compounds from the ground level to above the canopy were also measured. In order to characterize concentrations of speciated biogenic VOC (BVOC) in leaves, we analyzed leaf content by GC-MS (Gas Chromatography-Mass Spectrometery) regularly throughout the year. We also characterize in more detail concentrations of speciated BVOC in the air above the orchard by in-situ GC-MS during a few weeks in spring flowering and summer periods. Here we report concentrations and fluxes of the main VOC species emitted by the orchard, discuss how fluxes measured in the field relate to previous studies made with plant enclosures, and describe how VOC content in leaves and emissions change during the year in response to phenological and environmental parameters. The orchard was a source of monoterpenes and oxygenated VOC. The highest emissions were observed during the springtime flowering period, with mid-day fluxes above 2 nmol m-2 s-1 for methanol and up to 1 nmol m-2 s-1 for acetone and monoterpenes. During hot summer days emissions were not as high as we expected considering the known dependence of biogenic emissions on temperature. We provide evidence

  20. Seasonal cycles of biogenic volatile organic compound fluxes and concentrations in a California citrus orchard

    NASA Astrophysics Data System (ADS)

    Fares, S.; Park, J.-H.; Gentner, D. R.; Weber, R.; Ormeño, E.; Karlik, J.; Goldstein, A. H.

    2012-10-01

    Orange trees are widely cultivated in Mediterranean climatic regions where they are an important agricultural crop. Citrus have been characterized as emitters of volatile organic compounds (VOC) in chamber studies under controlled environmental conditions, but an extensive characterization at field scale has never been performed using modern measurement methods, and is particularly needed considering the complex interactions between the orchards and the polluted atmosphere in which Citrus is often cultivated. For one year, in a Valencia orange orchard in Exeter, California, we measured fluxes using PTRMS (Proton Transfer Reaction Mass Spectrometer) and eddy covariance for the most abundant VOC typically emitted from citrus vegetation: methanol, acetone, and isoprenoids. Concentration gradients of additional oxygenated and aromatic compounds from the ground level to above the canopy were also measured. In order to characterize concentrations of speciated biogenic VOC (BVOC) in leaves, we analyzed leaf content by GC-MS (Gas Chromatography - Mass Spectrometery) regularly throughout the year. We also characterized in more detail concentrations of speciated BVOC in the air above the orchard by in-situ GC-MS during a few weeks in spring flowering and summer periods. Here we report concentrations and fluxes of the main VOC species emitted by the orchard, discuss how fluxes measured in the field relate to previous studies made with plant enclosures, and describe how VOC content in leaves and emissions change during the year in response to phenological and environmental parameters. The orchard was a source of monoterpenes and oxygenated VOC. The highest emissions were observed during the springtime flowering period, with mid-day fluxes above 2 nmol m-2 s-1 for methanol and up to 1 nmol m-2 s-1 for acetone and monoterpenes. During hot summer days emissions were not as high as we expected considering the known dependence of biogenic emissions on temperature. We provide

  1. Annual cycle of volatile organic compound exchange between a boreal pine forest and the atmosphere

    NASA Astrophysics Data System (ADS)

    Rantala, P.; Aalto, J.; Taipale, R.; Ruuskanen, T. M.; Rinne, J.

    2015-06-01

    Long-term flux measurements of volatile organic compounds (VOC) over boreal forests are rare, although the forests are known to emit considerable amounts of VOCs into the atmosphere. Thus, we measured fluxes of several VOCs and oxygenated VOCs over a Scots pine dominated boreal forest semi-continuously between May 2010 and December 2013. The VOC profiles were obtained with a proton-transfer-reaction mass-spectrometry, and the fluxes were calculated using vertical concentration profiles and the surface layer profile method connected to the Monin-Obukhov similarity theory. In total fluxes that differed significantly from zero on a monthly basis were observed for 14 out 27 measured masses. Monoterpenes had the highest net emission in all seasons and statistically significant positive fluxes were detected from March until November. Other important compounds emitted were methanol, ethanol/formic acid, acetone and isoprene/MBO. Oxygenated VOCs showed also deposition fluxes that were statistically different from zero. Isoprene/methylbutenol and monoterpene fluxes followed well the traditional isoprene algorithm and the hybrid algorithm, respectively. Emission potentials of monoterpenes were largest in late spring and fall which was possibly driven by growth processes and decaying of soil litter, respectively. Conversely, largest emission potentials of isoprene/methylbutenol were found in July. Thus, we concluded that most of the emissions of m/z 69 at the site consisted of isoprene that originated from broadleaved trees. Methanol had deposition fluxes especially before sunrise. This can be connected to water films on surfaces. Based on this assumption, we were able to build an empirical algorithm for bi-directional methanol exchange that described both emission term and deposition term. Methanol emissions were highest in May and June and deposition level increased towards fall, probably as a result of increasing relative humidity levels leading to predominance of

  2. Annual cycle of volatile organic compound exchange between a boreal pine forest and the atmosphere

    NASA Astrophysics Data System (ADS)

    Rantala, P.; Aalto, J.; Taipale, R.; Ruuskanen, T. M.; Rinne, J.

    2015-10-01

    Long-term flux measurements of volatile organic compounds (VOC) over boreal forests are rare, although the forests are known to emit considerable amounts of VOCs into the atmosphere. Thus, we measured fluxes of several VOCs and oxygenated VOCs over a Scots-pine-dominated boreal forest semi-continuously between May 2010 and December 2013. The VOC profiles were obtained with a proton transfer reaction mass spectrometry, and the fluxes were calculated using vertical concentration profiles and the surface layer profile method connected to the Monin-Obukhov similarity theory. In total fluxes that differed significantly from zero on a monthly basis were observed for 13 out of 27 measured masses. Monoterpenes had the highest net emission in all seasons and statistically significant positive fluxes were detected from March until October. Other important compounds emitted were methanol, ethanol+formic acid, acetone and isoprene+methylbutenol. Oxygenated VOCs showed also deposition fluxes that were statistically different from zero. Isoprene+methylbutenol and monoterpene fluxes followed well the traditional isoprene algorithm and the hybrid algorithm, respectively. Emission potentials of monoterpenes were largest in late spring and autumn which was possibly driven by growth processes and decaying of soil litter, respectively. Conversely, largest emission potentials of isoprene+methylbutenol were found in July. Thus, we concluded that most of the emissions of m/z 69 at the site consisted of isoprene that originated from broadleaved trees. Methanol had deposition fluxes especially before sunrise. This can be connected to water films on surfaces. Based on this assumption, we were able to build an empirical algorithm for bi-directional methanol exchange that described both emission term and deposition term. Methanol emissions were highest in May and June and deposition level increased towards autumn, probably as a result of increasing relative humidity levels leading to

  3. Preliminary analysis of compound systems based on high temperature fuel cell, gas turbine and Organic Rankine Cycle

    NASA Astrophysics Data System (ADS)

    Sánchez, D.; Muñoz de Escalona, J. M.; Monje, B.; Chacartegui, R.; Sánchez, T.

    This article presents a novel proposal for complex hybrid systems comprising high temperature fuel cells and thermal engines. In this case, the system is composed by a molten carbonate fuel cell with cascaded hot air turbine and Organic Rankine Cycle (ORC), a layout that is based on subsequent waste heat recovery for additional power production. The work will credit that it is possible to achieve 60% efficiency even if the fuel cell operates at atmospheric pressure. The first part of the analysis focuses on selecting the working fluid of the Organic Rankine Cycle. After a thermodynamic optimisation, toluene turns out to be the most efficient fluid in terms of cycle performance. However, it is also detected that the performance of the heat recovery vapour generator is equally important, what makes R245fa be the most interesting fluid due to its balanced thermal and HRVG efficiencies that yield the highest global bottoming cycle efficiency. When this fluid is employed in the compound system, conservative operating conditions permit achieving 60% global system efficiency, therefore accomplishing the initial objective set up in the work. A simultaneous optimisation of gas turbine (pressure ratio) and ORC (live vapour pressure) is then presented, to check if the previous results are improved or if the fluid of choice must be replaced. Eventually, even if system performance improves for some fluids, it is concluded that (i) R245fa is the most efficient fluid and (ii) the operating conditions considered in the previous analysis are still valid. The work concludes with an assessment about safety-related aspects of using hydrocarbons in the system. Flammability is studied, showing that R245fa is the most interesting fluid also in this regard due to its inert behaviour, as opposed to the other fluids under consideration all of which are highly flammable.

  4. Triaxial MMG investigation during FES-induced cycle movements

    NASA Astrophysics Data System (ADS)

    Gelain, M. C.; Nogueira-Neto, G. N.; Nohama, P.; Gewehr, P. M.

    2016-04-01

    Spinal cord injury is damage to the spinal cord that results in loss of functions, causes muscle, joint and bone deficits, moreover it increases the muscle tone level. FEScycling is an alternative rehabilitation process to conserve the musculoskeletal system affected by the injury in the functional state. The aim of this study is to get the legs bilaterally synchronized by FES and compare MMG signal responses. The preliminary protocol consists of five consecutive contractions. The first and the last contractions were discarded and the three intermediate contractions were analyzed. A ratio between MMG values of muscle responses during propulsion and return of pedalling phases was calculated for each cycle and each leg. The applied FES profile consisted of pulse and burst on time of 250 us and 5 ms and frequencies of 1000 Hz and 20 Hz, respectively. Results showed that greater MMG RMS values tend to occur during the propulsion phase than in the return phase. MMG Z axis of RLL and MMG X axis of LLL were the axes that presented the greatest ratios. The MMG RMS signal showed that greater values tend to occur during the propulsion phase than in the return phase of the same thigh.

  5. Ziyuglycoside II induces cell cycle arrest and apoptosis through activation of ROS/JNK pathway in human breast cancer cells.

    PubMed

    Zhu, Xue; Wang, Ke; Zhang, Kai; Zhu, Ling; Zhou, Fanfan

    2014-05-16

    Ziyuglycoside II, a triterpenoid saponin compound extracted from Sanguisorba officinalis L., has been reported to have a wide range of clinical applications including anti-cancer effect. In this study, the anti-proliferative effect of ziyuglycoside II in two classic human breast cancer cell lines, MCF-7 and MDA-MB-231, was extensively investigated. Our study indicated that ziyuglycoside II could effectively induce G2/M phase arrest and apoptosis in both cell lines. Cell cycle blocking was associated with the down-regulation of Cdc25C, Cdc2, cyclin A and cyclin B1 as well as the up-regulation of p21/WAF1, phospho-Cdc25C and phospho-Cdc2. Ziyuglycoside II treatment also induced reactive oxygen species (ROS) production and apoptosis by activating the extrinsic/Fas/FasL pathway as well as the intrinsic/mitochondrial pathway. More importantly, the c-Jun NH2-terminal kinase (JNK), a downstream target of ROS, was found to be a critical mediator of ziyuglycoside II-induced cell apoptosis. Further knockdown of JNK by siRNA could inhibit ziyuglycoside II-mediated apoptosis with attenuating the up-regulation of Bax and Fas/FasL as well as the down-regulation of Bcl-2. Taken together, the cell death of breast cancer cells in response to ziyuglycoside II was dependent upon cell cycle arrest and cell apoptosis via a ROS-dependent JNK activation pathway. Our findings may significantly contribute to the understanding of the anti-proliferative effect of ziyuglycoside II, in particular to breast carcinoma and provide novel insights into the potential application of such compound in breast cancer therapy. PMID:24680927

  6. Tunable ultraviolet laser-induced fluorescence detection of trace plastics and dissolved organic compounds in water

    NASA Astrophysics Data System (ADS)

    Sivaprakasam, Vasanthi; Killinger, Dennis K.

    2003-11-01

    We developed a tunable (220-285-nm) UV and fixed 266-nm laser-induced fluorescence (LIF) system using a spectrometer and a cooled CCD imaging detector to measure the excitation-emission matrix spectra of various compounds in water, including quinine sulfate and plastic compound bisphenol-A. The LIF instrument was used for the fast, nonspecific determination of trace amounts of dissolved organic compounds present in natural water supplies and various brand name bottled distilled water and bottled drinking water. Plastic-related compounds that leached out of plastic utensils and containers were also detected with this instrument. The sensitivity of the system was approximately 1-2 orders of magnitude better than that for a commercial system.

  7. Tunable ultraviolet laser-induced fluorescence detection of trace plastics and dissolved organic compounds in water.

    PubMed

    Sivaprakasam, Vasanthi; Killinger, Dennis K

    2003-11-20

    We developed a tunable (220-285-nm) UV and fixed 266-nm laser-induced fluorescence (LIF) system using a spectrometer and a cooled CCD imaging detector to measure the excitation-emission matrix spectra of various compounds in water, including quinine sulfate and plastic compound bisphenol-A. The LIF instrument was used for the fast, nonspecific determination of trace amounts of dissolved organic compounds present in natural water supplies and various brand name bottled distilled water and bottled drinking water. Plastic-related compounds that leached out of plastic utensils and containers were also detected with this instrument. The sensitivity of the system was approximately 1-2 orders of magnitude better than that for a commercial system. PMID:14658478

  8. Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy

    PubMed Central

    Hallett, Robin M.; Huang, Cheng; Motazedian, Ali; Auf der Mauer, Stefanie; Pond, Gregory R.; Hassell, John A.; Nordon, Robert E.; Draper, Jonathan S.

    2015-01-01

    Chemotherapy fails to provide durable cure for the majority of cancer patients. To identify mechanisms associated with chemotherapy resistance, we identified genes differentially expressed before and after chemotherapeutic treatment of breast cancer patients. Treatment response resulted in either increased or decreased cell cycle gene expression. Tumors in which cell cycle gene expression was increased by chemotherapy were likely to be chemotherapy sensitive, whereas tumors in which cell cycle gene transcripts were decreased by chemotherapy were resistant to these agents. A gene expression signature that predicted these changes proved to be a robust and novel index that predicted the response of patients with breast, ovarian, and colon tumors to chemotherapy. Investigations in tumor cell lines supported these findings, and linked treatment induced cell cycle changes with p53 signaling and G1/G0 arrest. Hence, chemotherapy resistance, which can be predicted based on dynamics in cell cycle gene expression, is associated with TP53 integrity. PMID:25749523

  9. Chemotherapy Drug Induced Discoordination of Mitochondrial Life Cycle Detected by Cardiolipin Fluctuation.

    PubMed

    Chao, Yu-Jen; Chan, Jui-Fen; Hsu, Yuan-Hao Howard

    2016-01-01

    Chemotherapy drugs have been prescribed for the systemic treatment of cancer. We selected three chemotherapy drugs, including methotrexate, mitomycine C and vincristine to inhibit the proliferation of HT1080 human fibrosarcoma cells in S, G2 and M phases of the cell cycle respectively. These chemotherapy drugs showed significant toxicity and growth inhibition to the cancer cells measured by MTT assay. After treated with a 50% inhibitory dosage for 48 hours, these cancer cells showed significant accumulation of cardiolipin (CL), which was a reverse trend of the nutritional deficiency induced arrest at G1 phase. The quantity of each CL species was further semi-quantitated by HPLC-ion trap mass spectrometer. Methotraxate treatment caused unique increases of acyl chain length on CL, which were the opposite of the serum starvation, mitomycine C and vincristine treatments. Although mitomycine C and vincristine have different mechanisms to induce cell cycle arrest, these two drugs displayed similar effects on decreasing chain length of CL. Continuation of CL synthesis during cell cycle arrest indicated the chemotherapy drugs resulting in the discoordination of the mitochondrial life cycle from the cell cycle and thus caused the accumulation of CL. These finding reveals that the pre-remodeling nascent CL accumulates during the methotraxate induced arrest; however, the post-remodeling mature CL accumulates during the mitomycine C and vincristine induced arrest after the synthesis phase. PMID:27627658

  10. Cycling-Induced Changes in the Entropy Profiles of Lithium Cobalt Oxide Electrodes

    DOE PAGESBeta

    Hudak, N. S.; Davis, L. E.; Nagasubramanian, G.

    2014-12-09

    Entropy profiles of lithium cobalt oxide (LiCoO2) electrodes were measured at various stages in the cycle life to examine performance degradation and cycling-induced changes, or lack thereof, in thermodynamics. LiCoO2 electrodes were cycled at C/2 rate in half-cells (vs. lithium anodes) up to 20 cycles or C/5 rate in full cells (vs. MCMB anodes) up to 500 cycles. The electrodes were then subjected to entropy measurements (∂E/∂T, where E is open-circuit potential and T is temperature) in half-cells at regular intervals over the approximate range 0.5 ≤ x ≤ 1 in LixCoO2. Despite significant losses in capacity upon cycling, neithermore » cycling rate resulted in any change to the overall shape of the entropy profile relative to an uncycled electrode, indicating retention of the basic LiCoO2 structure, lithium insertion mechanism, and thermodynamics. This confirms that cycling-induced performance degradation in LiCoO2 electrodes is primarily caused by kinetic barriers that increase with cycling. In the case of electrodes cycled at C/5, there was a subtle, quantitative, and gradual change in the entropy profile in the narrow potential range of the hexagonal-to-monoclinic phase transition. The observed change is indicative of a decrease in the intralayer lithium ordering that occurs at these potentials, and it demonstrates that a cyclinginduced structural disorder accompanies the kinetic degradation mechanisms.« less

  11. Cycling-Induced Changes in the Entropy Profiles of Lithium Cobalt Oxide Electrodes

    SciTech Connect

    Hudak, N. S.; Davis, L. E.; Nagasubramanian, G.

    2014-12-09

    Entropy profiles of lithium cobalt oxide (LiCoO2) electrodes were measured at various stages in the cycle life to examine performance degradation and cycling-induced changes, or lack thereof, in thermodynamics. LiCoO2 electrodes were cycled at C/2 rate in half-cells (vs. lithium anodes) up to 20 cycles or C/5 rate in full cells (vs. MCMB anodes) up to 500 cycles. The electrodes were then subjected to entropy measurements (∂E/∂T, where E is open-circuit potential and T is temperature) in half-cells at regular intervals over the approximate range 0.5 ≤ x ≤ 1 in LixCoO2. Despite significant losses in capacity upon cycling, neither cycling rate resulted in any change to the overall shape of the entropy profile relative to an uncycled electrode, indicating retention of the basic LiCoO2 structure, lithium insertion mechanism, and thermodynamics. This confirms that cycling-induced performance degradation in LiCoO2 electrodes is primarily caused by kinetic barriers that increase with cycling. In the case of electrodes cycled at C/5, there was a subtle, quantitative, and gradual change in the entropy profile in the narrow potential range of the hexagonal-to-monoclinic phase transition. The observed change is indicative of a decrease in the intralayer lithium ordering that occurs at these potentials, and it demonstrates that a cyclinginduced structural disorder accompanies the kinetic degradation mechanisms.

  12. G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound.

    PubMed

    Cabrera, Maia; Gomez, Natalia; Remes Lenicov, Federico; Echeverría, Emiliana; Shayo, Carina; Moglioni, Albertina; Fernández, Natalia; Davio, Carlos

    2015-01-01

    Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4'-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies. PMID:26360247

  13. G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound

    PubMed Central

    Cabrera, Maia; Gomez, Natalia; Remes Lenicov, Federico; Echeverría, Emiliana; Shayo, Carina; Moglioni, Albertina; Fernández, Natalia; Davio, Carlos

    2015-01-01

    Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4’-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies. PMID:26360247

  14. The Phenomenology of Ion Implantation-Induced Blistering and Thin-Layer Splitting in Compound Semiconductors

    NASA Astrophysics Data System (ADS)

    Singh, R.; Christiansen, S. H.; Moutanabbir, O.; Gösele, U.

    2010-10-01

    Hydrogen and/or helium implantation-induced surface blistering and layer splitting in compound semiconductors such as InP, GaAs, GaN, AlN, and ZnO are discussed. The blistering phenomenon depends on many parameters such as the semiconductor material, ion fluence, ion energy, and implantation temperature. The optimum values of these parameters for compound semiconductors are presented. The blistering and splitting processes in silicon have been studied in detail, motivated by the fabrication of the widely used silicon-on-insulator wafers. Hence, a comparison of the blistering process in Si and compound semiconductors is also presented. This comparative study is technologically relevant since ion implantation-induced layer splitting combined with direct wafer bonding in principle allows the transfer of any type of semiconductor layer onto any foreign substrate of choice—the technique is known as the ion-cut or Smart-Cut™ method. For the aforementioned compound semiconductors, investigations regarding layer transfer using the ion-cut method are still in their infancy. We report feasibility studies of layer transfer by the ion-cut method for some of the most important and widely used compound semiconductors. The importance of characteristic values for successful wafer bonding such as wafer bow and surface flatness as well as roughness are discussed, and difficulties in achieving some of these values are pointed out.

  15. 2,5-Dimethyl-celecoxib inhibits cell cycle progression and induces apoptosis in human leukemia cells.

    PubMed

    Sobolewski, Cyril; Rhim, Jiyun; Legrand, Noémie; Muller, Florian; Cerella, Claudia; Mack, Fabienne; Chateauvieux, Sébastien; Kim, Jeoung-Gyun; Yoon, Ah-Young; Kim, Kyu-Won; Dicato, Mario; Diederich, Marc

    2015-11-01

    Cyclooxygenase-2 (COX-2) is an essential regulator of cancer promotion and progression. Extensive efforts to target this enzyme have been developed to reduce growth of cancer cells for chemopreventive and therapeutic reasons. In this context, cyclooxygenase-2 inhibitors present interesting antitumor effects. However, inhibition of COX-2 by anti-COX-2 compounds such as celecoxib was recently associated with detrimental cardiovascular side effects limiting their clinical use. As many anticancer effects of celecoxib are COX-2 independent, analogs such as 2,5-dimethyl-celecoxib (DMC), which lacks COX-2-inhibitory activity, represent a promising alternative strategy. In this study, we investigated the effect of this molecule on growth of hematologic cancer cell lines (U937, Jurkat, Hel, Raji, and K562). We found that this molecule is able to reduce the growth and induces apoptosis more efficiently than celecoxib in all the leukemic cell lines tested. Cell death was associated with downregulation of Mcl-1 protein expression. We also found that DMC induces endoplasmic reticulum stress, which is associated with a decreased of GRP78 protein expression and an alteration of cell cycle progression at the G1/S transition in U937 cells. Accordingly, typical downregulation of c-Myc and cyclin D1 and an upregulation of p27 were observed. Interestingly, for shorter time points, an alteration of mitotic progression, associated with the downregulation of survivin protein expression was observed. Altogether, our data provide new evidence about the mode of action of this compound on hematologic malignancies. PMID:26330537

  16. Xanthohumol induces apoptosis and S phase cell cycle arrest in A549 non-small cell lung cancer cells

    PubMed Central

    Yong, Wai Kuan; Ho, Yen Fong; Malek, Sri Nurestri Abd

    2015-01-01

    Background: Xanthohumol, a major prenylated chalcone found in female hop plant, Humulus lupulus, was reported to have various chemopreventive and anti-cancer properties. However, its apoptotic effect on human alveolar adenocarcinoma cell line (A549) of non-small cell lung cancer (NSCLC) was unknown. Objective: This study aimed to investigate the effects of xanthohumol on apoptosis in A549 human NSCLC cells. Materials and Methods: A549 cell proliferation was determined by sulforhodamine B assay. Morphological changes of the cells were studied via phase contrast and fluorescent microscopy. Induction of apoptosis was assessed by Annexin-V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining, DNA fragmentation (TUNEL) assay mitochondrial membrane potential assay, cell cycle analysis, and caspase activity studies. Results: Xanthohumol was found to decrease cell proliferation in A549 cells but had relatively low cytotoxicity on normal human lung fibroblast cell line (MRC-5). Typical cellular and nuclear apoptotic features were also observed in A549 cells treated with xanthohumol. Onset of apoptosis in A549 cells was further confirmed by externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells after treatment. Xanthohumol induced accumulation of cells in sub G1 and S phase based on cell cycle analysis and also increased the activities of caspase-3, -8, and -9. Conclusion: This work suggests that xanthohumol as an apoptosis inducer, may be a potent therapeutic compound for NSCLC. PMID:26664015

  17. Potential for ion-induced nucleation of volatile organic compounds by radon decay in indoor environments

    SciTech Connect

    Daisey, J.M.

    1991-11-01

    There is considerable interest in the ``unattached`` fraction of radon progeny in indoor air because of its significance to the estimation of the risks of radon exposure. Because of its high mobility in air, the unattached fraction is more efficiently deposited in the respiratory tract. Variation in the diameter of the ``unattached`` fraction and in its diffusion coefficient can be due to clustering of other atmospheric species around the {sup 218}PoO{sub 2}{sup +} ion. The purpose of this study was to investigate the potential for the formation of clusters of vapor phase organic compounds, found in indoor air, around the {sup 218}PoO{sub 2}{sup +} ion and to determine which were most likely to form clusters. A secondary purpose was to provide a compilation of measurements of indoor organic compounds for future experiments and theoretical calculations by the radon research community. The classical charged liquid droplet theory (Thomson equation) was used to estimate the Gibbs free energy of ion-induced nucleation and to provide an indication of the indoor organic compounds most likely to undergo ion-induced nucleation. Forty-four volatile and semi-volatile organic compounds out of the more than 300 which have been reported in indoor air were investigated. Water vapor was included for comparison. The results indicate that there is a potential for the formation of clusters of organic compounds around the {sup 218}PoO{sub 2}{sup +} ion. The compounds with the greatest potential for cluster formation are the volatile oxidized hydrocarbons (e.g., n-butanol, phenol, hexanal, nonanal, benzaldehyde, the ketones and the acetates) and the semi-volatile organic compounds (pentachlorophenol, nicotine, chlordane, chlorpyrifos).

  18. Potential for ion-induced nucleation of volatile organic compounds by radon decay in indoor environments

    SciTech Connect

    Daisey, J.M.

    1991-11-01

    There is considerable interest in the unattached'' fraction of radon progeny in indoor air because of its significance to the estimation of the risks of radon exposure. Because of its high mobility in air, the unattached fraction is more efficiently deposited in the respiratory tract. Variation in the diameter of the unattached'' fraction and in its diffusion coefficient can be due to clustering of other atmospheric species around the {sup 218}PoO{sub 2}{sup +} ion. The purpose of this study was to investigate the potential for the formation of clusters of vapor phase organic compounds, found in indoor air, around the {sup 218}PoO{sub 2}{sup +} ion and to determine which were most likely to form clusters. A secondary purpose was to provide a compilation of measurements of indoor organic compounds for future experiments and theoretical calculations by the radon research community. The classical charged liquid droplet theory (Thomson equation) was used to estimate the Gibbs free energy of ion-induced nucleation and to provide an indication of the indoor organic compounds most likely to undergo ion-induced nucleation. Forty-four volatile and semi-volatile organic compounds out of the more than 300 which have been reported in indoor air were investigated. Water vapor was included for comparison. The results indicate that there is a potential for the formation of clusters of organic compounds around the {sup 218}PoO{sub 2}{sup +} ion. The compounds with the greatest potential for cluster formation are the volatile oxidized hydrocarbons (e.g., n-butanol, phenol, hexanal, nonanal, benzaldehyde, the ketones and the acetates) and the semi-volatile organic compounds (pentachlorophenol, nicotine, chlordane, chlorpyrifos).

  19. Random transverse motion-induced spatial compounding for fiber bundle imaging.

    PubMed

    Cheon, Gyeong Woo; Cha, Jaepyeong; Kang, Jin U

    2014-08-01

    We propose and demonstrate a novel fiber bundle imaging based on spatial compounding induced by random transverse motion to remove the pixelation effect, to improve resolution, and to increase image quality. The experimental results using a USAF target and pyramidal neuron cell showed that 20-frame compounding improved image quality (contrast-to-noise ratio by >9  dB, global SNR by >6  dB, equivalent number of looks by >1.8  times, and 1/β by >1.5  times), resolution by better than 2 μm, and completely eliminated pixelation artifact. PMID:25078179

  20. Cucurbitacin E Induces Cell Cycle G2/M Phase Arrest and Apoptosis in Triple Negative Breast Cancer

    PubMed Central

    Zhou, Zhongmei; Xia, Houjun; Qiu, Ming-Hua; Chen, Ceshi

    2014-01-01

    Triple negative breast cancer (TNBC) is a highly aggressive form of breast cancer resistant to many common treatments. In this study, we compared the effects of 12 phytochemical drugs on four cancer cell lines, and noticed that Cucurbitacin E (CuE) significantly inhibited TNBC cell growth by inducing cell cycle G2/M phase arrest and apoptosis. CuE reduced expression of Cyclin D1, Survivin, XIAP, Bcl2, and Mcl-1 in MDA-MB-468 and SW527, and within MDA-MB-468, CuE significantly increased activation of JNK and inhibited activation of AKT and ERK. Collectively, these results suggest that CuE may be a viable compound for developing novel TNBC therapeutics. PMID:25072848

  1. Parametric investigation of laser-induced fluorescence of solid-state uranyl compounds.

    PubMed

    Wang, Guangjun; Su, Yi; Monts, David L

    2008-10-23

    The combination of remote/standoff sensing and laser-induced fluorescence (LIF) spectroscopy shows potential for detection of uranyl (UO2(2+)) compounds. Uranyl compounds exhibit characteristic emission in the 450-600 nm (22,200 to 16,700 cm(-1)) spectral region when excited by wavelengths in the ultraviolet or in the short-wavelength portion of the visible spectrum. We report a parametric study of the effects of excitation wavelength [including 532 nm (18,797 cm(-1)), 355 nm (28,169 cm(-1)), and 266 nm (37,594 cm(-1))] and excitation laser power on solid-state uranium compounds. The uranium compounds investigated include uranyl nitrate, uranyl sulfate, uranyl oxalate, uranium dioxide, triuranium octaoxide, uranyl acetate, uranyl formate, zinc uranyl acetate, and uranyl phosphate. We observed the characteristic uranyl fluorescence spectrum from the uranium compounds except for uranium oxide compounds (which do not contain the uranyl moiety) and for uranyl formate, which has a low fluorescence quantum yield. Relative uranyl fluorescence intensity is greatest for 355 nm excitation, and the order of decreasing fluorescence intensity with excitation wavelength (relative intensity/laser output) is 355 nm > 266 nm > 532 nm. For 532 nm excitation, the emission spectrum is produced by two-photon excitation. Uranyl fluorescence intensity increases linearly with increasing laser power, but the rate of fluorescence intensity increase is different for different emission bands. PMID:18823105

  2. Members Only: Hypoxia-Induced Cell-Cycle Activation in Cardiomyocytes.

    PubMed

    Sharma, Arun; Wu, Sean M

    2015-09-01

    A low level of cardiomyocyte turnover occurs in the adult mammalian heart, but the source of these new cells remains unknown. Kimura et al., 2015 utilized a novel hypoxia-induced fate mapping system to identify a rare population of adult cardiomyocytes undergoing cell-cycle entry and expansion in healthy adult hearts and following ischemic injury. PMID:26331604

  3. Astaxanthin Inhibits Proliferation and Induces Apoptosis and Cell Cycle Arrest of Mice H22 Hepatoma Cells.

    PubMed

    Shao, Yiye; Ni, Yanbo; Yang, Jing; Lin, Xutao; Li, Jun; Zhang, Lixia

    2016-01-01

    BACKGROUND It is widely recognized that astaxanthin (ASX), a member of the carotenoid family, has strong biological activities including antioxidant, anti-inflammation, and immune-modulation activities. Previous studies have confirmed that ASX can effectively inhibit hepatoma cells in vitro. MATERIAL AND METHODS MTT was used to assay proliferation of mice H22 cells, and flow cytometry was used to determine apoptosis and cell cycle arrest of H22 cells in vitro and in vivo. Moreover, anti-tumor activity of ASX was observed in mice. RESULTS ASX inhibited the proliferation of H22 cells, promoted cell necrosis, and induced cell cycle arrest in G2 phase in vitro and in vivo. CONCLUSIONS This study indicated that ASX can inhibit proliferation and induce apoptosis and cell cycle arrest in mice H22 hepatoma cells in vitro and in vivo. PMID:27333866

  4. Astaxanthin Inhibits Proliferation and Induces Apoptosis and Cell Cycle Arrest of Mice H22 Hepatoma Cells

    PubMed Central

    Shao, Yiye; Ni, Yanbo; Yang, Jing; Lin, Xutao; Li, Jun; Zhang, Lixia

    2016-01-01

    Background It is widely recognized that astaxanthin (ASX), a member of the carotenoid family, has strong biological activities including antioxidant, anti-inflammation, and immune-modulation activities. Previous studies have confirmed that ASX can effectively inhibit hepatoma cells in vitro. Material/Methods MTT was used to assay proliferation of mice H22 cells, and flow cytometry was used to determine apoptosis and cell cycle arrest of H22 cells in vitro and in vivo. Moreover, anti-tumor activity of ASX was observed in mice. Results ASX inhibited the proliferation of H22 cells, promoted cell necrosis, and induced cell cycle arrest in G2 phase in vitro and in vivo. Conclusions This study indicated that ASX can inhibit proliferation and induce apoptosis and cell cycle arrest in mice H22 hepatoma cells in vitro and in vivo. PMID:27333866

  5. Using Drosophila Larval Imaginal Discs to Study Low-Dose Radiation-Induced Cell Cycle Arrest

    PubMed Central

    Yan, Shian-Jang; Li, Willis X.

    2012-01-01

    Under genotoxic stress, activation of cell cycle checkpoint responses leads to cell cycle arrest, which allows cells to repair DNA damage before continuing to cycle. Drosophila larval epithelial sacs, called imaginal discs, are an excellent in vivo model system for studying radiation-induced cell cycle arrest. Larval imaginal discs go into cell cycle arrest after being subjected to low-dose irradiation, are subject to easy genetic manipulation, are not crucial for survival of the organism, and can be dissected easily for further molecular or cellular analysis. In this chapter, we describe methods for assessing low-dose irradiation-induced cell cycle arrest. Mitotic cells are identified by immunofluorescence staining for the mitotic marker phosphorylated histone H3 (phospho-histone H3 or pH3). When wandering third-instar control larvae, without transgene expression, are exposed to 500 rads of X-ray or γ-ray irradiation, the number of pH3-positive cells in wing imaginal discs is reduced from hundreds before irradiation to approximately 30 after irradiation, with an equal distribution between the anterior and posterior compartments (Yan et al., 2011, FASEB J). Using the GAL4/UAS system, RNAi, cDNA, or microRNA sponge transgenes can be expressed in the posterior compartment of the wing disc using drivers such as engrailed (en)-Gal4, while the anterior compartment serves as an internal control. This approach makes it possible to do genome-wide genetic screening for molecules involved in radiation-induced cell cycle arrest. PMID:21870287

  6. Using Drosophila larval imaginal discs to study low-dose radiation-induced cell cycle arrest.

    PubMed

    Yan, Shian-Jang; Li, Willis X

    2011-01-01

    Under genotoxic stress, activation of cell cycle checkpoint responses leads to cell cycle arrest, which allows cells to repair DNA damage before continuing to cycle. Drosophila larval epithelial sacs, called imaginal discs, are an excellent in vivo model system for studying radiation-induced cell cycle arrest. Larval imaginal discs go into cell cycle arrest after being subjected to low-dose irradiation, are subject to easy genetic manipulation, are not crucial for survival of the organism, and can be dissected easily for further molecular or cellular analysis. In this chapter, we describe methods for assessing low-dose irradiation-induced cell cycle arrest. Mitotic cells are identified by immunofluorescence staining for the mitotic marker phosphorylated histone H3 (phospho-histone H3 or pH3). When wandering third-instar control larvae, without transgene expression, are exposed to 500 rads of X-ray or γ-ray irradiation, the number of pH3-positive cells in wing imaginal discs is reduced from hundreds before irradiation to approximately 30 after irradiation, with an equal distribution between the anterior and posterior compartments (Yan et al., 2011, FASEB J). Using the GAL4/UAS system, RNAi, cDNA, or microRNA sponge transgenes can be expressed in the posterior compartment of the wing disc using drivers such as engrailed (en)-Gal4, while the anterior compartment serves as an internal control. This approach makes it possible to do genome-wide genetic screening for molecules involved in radiation-induced cell cycle arrest. PMID:21870287

  7. Gravitational effects of process-induced dislocations in silicon. [during thermal cycling

    NASA Technical Reports Server (NTRS)

    Porter, W. A.; Parker, D. L.

    1974-01-01

    Matters pertaining to semiconductor device fabrication were studied in terms of the influence of gravity on the production of dislocations in silicon wafers during thermal cycling in a controlled ambient where no impurities are present and oxidation is minimal. Both n-type and p-type silicon wafers having a diameter of 1.25 in to 1.5 in, with fixed orientation and resistivity values, were used. The surface dislocation densities were measured quantitatively by the Sirtl etch technique. The results show two significant features of the plastic flow phenomenon as it is related to gravitational stress: (1) the density of dislocations generated during a given thermal cycle is directly related to the duration of the cycle; and (2) the duration of the thermal cycle required to produce a given dislocation density is inversely related to the equilibrium temperature. Analysis of the results indicates that gravitational stress is instrumental in process-induced defect generation.

  8. Spectroscopic properties and laser induced fluorescence determination of some endocrine disrupting compounds.

    PubMed

    Benmansour, Badr; Stephan, Ludovic; Cabon, Jean-Yves; Deschamps, Laure; Giamarchi, Philippe

    2011-05-01

    This work presents spectroscopic properties of some Endocrine Disrupting Compounds (EDCs), frequently found in food and in natural water. Studied molecules belong to the groups of phenolic and phthalate EDCs. In a first part, we have examined their absorption and fluorescence properties. Fluorescence emission wavelengths are about 300 nm for phenolic compounds and 360 nm for phtalate compounds; main excitation wavelengths being comprised between 210 nm and 230 nm. Fluorescence lifetimes measured are short (about 4 ns) and the fluorescence quantum yield has been determined. In a second part, to avoid the time consuming solvent extraction step, an analytical application to evaluate the performance of a direct analysis by laser induced fluorescence spectroscopy of ECDs traces in tap water and in raw water is presented. Good detection limits have been obtained, i.e.: 0.35 µg.L(-1) of chlorophenol in tap water, which are always lower than the reported Predictive Non Efficient Concentration (PNEC). PMID:20084436

  9. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    SciTech Connect

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun; Zheng, Lemin; Zhou, Boda; Zhang, Wei; Lv, He; Yuan, Yun

    2014-03-28

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21.

  10. Retama monosperma n-hexane extract induces cell cycle arrest and extrinsic pathway-dependent apoptosis in Jurkat cells

    PubMed Central

    2014-01-01

    Background Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), locally named as “R’tam”, is an annual and spontaneous plant belonging to the Fabaceae family. In Morocco, Retama genus is located in desert regions and across the Middle Atlas and it has been widely used in traditional medicine in many countries. In this study, we show that Retama monosperma hexane extract presents significant anti-leukemic effects against human Jurkat cells. Methods Human Jurkat cells, together with other cell lines were screened with different concentrations of Retama monosperma hexane extract at different time intervals. Growth inhibition was determined using luminescent-based viability assays. Cell cycle arrest and apoptosis were measured by flow cytometry analysis. Combined caspase 3 and 7 activities were measured using luminometric caspase assays and immunoblots were performed to analyze expression of relevant pro- and anti-apoptotic proteins. GC-MS were used to determine the chemical constituents of the active extract. Results Retama monosperma hexane extract (Rm-HE) showed significant cytotoxicity against Jurkat cells, whereas it proved to be essentially ineffective against both normal mouse fibroblasts (NIH3T3) and normal lymphocytes (TK-6). Cytometric analysis indicated that Rm-HE promoted cell cycle arrest and apoptosis induction accompanied by DNA damage induction indicated by an increase in p-H2A.X levels. Rm-HE induced apoptosis was partially JNK-dependent and characterized by an increase in Fas-L levels together with activation of caspases 8, 3, 7 and 9, whereas neither the pro-apoptotic nor anti-apoptotic mitochondrial membrane proteins analyzed were significantly altered. Chemical identification analysis indicated that α-linolenic acid, campesterol, stigmasterol and sitosterol were the major bioactive components within the extract. Conclusions Our data suggest that bioactive compounds present in Rm-HE show significant anti leukemic activity inducing

  11. Difference of cell cycle arrests induced by lidamycin in human breast cancer cells.

    PubMed

    Liu, Xia; He, Hongwei; Feng, Yun; Zhang, Min; Ren, Kaihuan; Shao, Rongguang

    2006-02-01

    Lidamycin (LDM) is a member of the enediyne antibiotic family. It is undergoing phase I clinical trials in China as a potential chemotherapeutic agent. In the present study, we investigated the mechanism by which LDM induced cell cycle arrest in human breast cancer cells. The results showed that LDM induced G1 arrest in p53 wild-type MCF-7 cells at low concentrations, and caused both G1 and G2/M arrests at higher concentrations. In contrast, LDM induced only G2/M arrest in p53-mutant MCF-7/DOX cells. Western blotting analysis indicated that LDM-induced G1 and G2/M arrests in MCF-7 cells were associated with an increase of p53 and p21, and a decrease of phosphorylated retinoblastoma tumor suppressor protein, cyclin-dependent kinase (Cdk), Cdc2 and cyclin B1 protein levels. However, LDM-induced G2/M arrest in MCF-7/DOX cells was correlated with the reduction of cyclin B1 expression. Further study indicated that the downregulation of cyclin B1 by LDM in MCF-7 cells was associated with decreasing cyclin B1 mRNA levels and promoting protein degradation, whereas it was only due to inducing cyclin B1 protein degradation in MCF-7/DOX cells. In addition, activation of checkpoint kinases Chk1 or Chk2 maybe contributed to LDM-induced cell cycle arrest. Taken together, we provide the first evidence that LDM induces different cell cycle arrests in human breast cancer cells, which are dependent on drug concentration and p53 status. These findings are helpful in understanding the molecular anti-cancer mechanisms of LDM and support its clinical trials. PMID:16428935

  12. Lipoic acid suppresses compound 48/80-induced anaphylaxis-like reaction

    PubMed Central

    Choi, Yun Ho; Chai, Ok Hee; Han, Eui-Hyeog; Choi, Su-Young; Kim, Hyoung Tae

    2010-01-01

    Alpha-lipoic acid (LA), a naturally occurring dithiol compound, is an essential cofactor in metabolic reactions involved in energy utilization. LA improves glycemic control, reduces diabetic polyneuropathies, atherosclerosis, and allergic inflammation. The effects of LA on mast cell-mediated anaphylactic reactions, however, are unknown. LA dose-dependently inhibited systemic and passive cutaneous anaphylaxis-like reactions in mice induced by compound 48/80, a condensation product of N-methyl-p-methoxyphenethylamine and formaldehyde. Pretreatment with LA, prior to induction of the systemic anaphylaxis-like reaction with compound 48/80, reduced plasma histamine levels in a dose-dependent manner. In our in vitro study, LA decreased histamine release from rat peritoneal mast cells (RPMCs) triggered by compound 48/80. Moreover, an increase in calcium uptake activated by compound 48/80 was inhibited by LA. LA also significantly elevated intracellular cyclic adenosine-3',5' monophosphate (cAMP) levels in RPMCs. This inhibition of mediator release from RPMCs may be due to inhibition of calcium uptake and augmentation of intracellular cAMP levels. Based on these results, we suggest that LA may be a potential remedy for allergy-related diseases. PMID:21267406

  13. The natural chlorine cycle - Formation of the carcinogenic and greenhouse gas compound chloroform in drinking water reservoirs.

    PubMed

    Forczek, Sándor T; Pavlík, Milan; Holík, Josef; Rederer, Luděk; Ferenčík, Martin

    2016-08-01

    Chlorine cycle in natural ecosystems involves formation of low and high molecular weight organic compounds of living organisms, soil organic matter and atmospherically deposited chloride. Chloroform (CHCl3) and adsorbable organohalogens (AOX) are part of the chlorine cycle. We attempted to characterize the dynamical changes in the levels of total organic carbon (TOC), AOX, chlorine and CHCl3 in a drinking water reservoir and in its tributaries, mainly at its spring, and attempt to relate the presence of AOX and CHCl3 with meteorological, chemical or biological factors. Water temperature and pH influence the formation and accumulation of CHCl3 and affect the conditions for biological processes, which are demonstrated by the correlation between CHCl3 and ΣAOX/Cl(-) ratio, and also by CHCl3/ΣAOX, CHCl3/AOXLMW, CHCl3/ΣTOC, CHCl3/TOCLMW and CHCl3/Cl(-) ratios in different microecosystems (e.g. old spruce forest, stagnant acidic water, humid and warm conditions with high biological activity). These processes start with the biotransformation of AOX from TOC, continue via degradation of AOX to smaller molecules and further chlorination, and finish with the formation of small chlorinated molecules, and their subsequent volatilization and mineralization. The determined concentrations of chloroform result from a dynamic equilibrium between its formation and degradation in the water; in the Hamry water reservoir, this results in a total amount of 0.1-0.7 kg chloroform and 5.2-15.4 t chloride. The formation of chloroform is affected by Cl(-) concentration, by concentrations and ratios of biogenic substrates (TOC and AOX), and by the ratios of the substrates and the product (feedback control by chloroform itself). PMID:27231877

  14. Cell cycle re-entry sensitizes podocytes to injury induced death.

    PubMed

    Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

    2016-07-17

    Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy. PMID:27232327

  15. Two new isoquinoline alkaloids from Scolopendra subspinipes mutilans induce cell cycle arrest and apoptosis in human glioma cancer U87 cells.

    PubMed

    Ding, Dan; Guo, Ya-Ru; Wu, Rui-Ling; Qi, Wei-Yan; Xu, Han-Mei

    2016-04-01

    Two new isoquinoline alkaloids 1-2 and seven known compounds 3-9 were isolated from the ethanol extract of centipede Scolopendra subspinipes mutilans L. Koch. The structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR, and HRESIMS. Compounds 1-2 exhibited good cytotoxicity with IC50 values ranging from 1.19 to 31.28μM against six human cancer cell lines and low cytotoxicity against human normal liver L-02 cell lines, suggesting that compounds 1-2 had high specific cytotoxicity on human cancer cell lines. Further analyses showed that compounds 1-2 inhibited U87 cells proliferation by arresting cell cycle progress at G0/G1 phase and inducing apoptosis through loss of mitochondrial membrane potential (MMP), activation of caspase 9/3 and down-regulation of the Bcl-2/Bax protein ratio. The results suggest that compounds 1-2 induce apoptosis in U87 cells through the mitochondria apoptosis pathway, and they deserve further research as potential anti-glioma cancer agents. PMID:26947248

  16. Raman spectrum reveals the cell cycle arrest of Triptolide-induced leukemic T-lymphocytes apoptosis

    NASA Astrophysics Data System (ADS)

    Zhang, Daosen; Feng, Yanyan; Zhang, Qinnan; Su, Xin; Lu, Xiaoxu; Liu, Shengde; Zhong, Liyun

    2015-04-01

    Triptolide (TPL), a traditional Chinese medicine extract, possesses anti-inflammatory and anti-tumor properties. Though some research results have implicated that Triptolide (TPL) can be utilized in the treatment of leukemia, it remains controversial about the mechanism of TPL-induced leukemic T-lymphocytes apoptosis. In this study, combining Raman spectroscopic data, principal component analysis (PCA) and atomic force microscopy (AFM) imaging, both the biochemical changes and morphological changes during TPL-induced cell apoptosis were presented. In contrast, the corresponding data during Daunorubicin (DNR)-induced cell apoptosis was also exhibited. The obtained results showed that Raman spectral changes during TPL-induced cell apoptosis were greatly different from DNR-induced cell apoptosis in the early stage of apoptosis but revealed the high similarity in the late stage of apoptosis. Moreover, above Raman spectral changes were respectively consistent with the morphological changes of different stages during TPL-induced apoptosis or DNR-induced apoptosis, including membrane shrinkage and blebbing, chromatin condensation and the formation of apoptotic bodies. Importantly, it was found that Raman spectral changes with TPL-induced apoptosis or DNR-induced apoptosis were respectively related with the cell cycle G1 phase arrest or G1 and S phase arrest.

  17. Vanadium-induced formation of thiadiazole and thiazoline compounds. Mononuclear and dinuclear oxovanadium(v) complexes with open-chain and cyclized thiosemicarbazone ligands.

    PubMed

    Rubcić, Mirta; Milić, Dalibor; Horvat, Gordan; Dilović, Ivica; Galić, Nives; Tomisić, Vladislav; Cindrić, Marina

    2009-11-28

    Reactions of the salicylaldehyde 4-phenylthiosemicarbazone (H(2)L) with selected vanadium(iv) and vanadium(v) precursors ([VO(acac)(2)], [VO(OAc)(2)], VOSO(4), [V(2)O(4)(acac)(2)]) were investigated under aerobic conditions in different alcohols (methanol, ethanol, propanol). In all examined cases mononuclear alkoxo vanadium(v) complexes [VOL(OR)] (1) (OR = OMe, OEt, OPr) were isolated as major products. On prolonged standing, mother liquids afforded dinuclear vanadium(v) complexes [V(2)O(3)(L(cycl))(2)(OR)(2)] (3) (OR = OMe, OEt, OPr), where L(cycl)(-) represents 1,3,4-thiadiazole ligand, formed by vanadium-induced oxidative cyclization of H(2)L. When [VO(acac)(2)] or [V(2)O(4)(acac)(2)] were used as precursors, in addition to products 1 and 3, a thiazoline derivative HL(acac)(cycl) (2) was isolated. This compound, formed by a reaction between acetylacetone and H(2)L, represented the second type of cyclic product. The products were characterized by IR and NMR spectroscopies, TG analysis, and in some cases by single-crystal X-ray diffraction. To the best of our knowledge, compounds [V(2)O(3)(L(cycl))(2)(OR)(2)] represent the first structurally characterized dinuclear vanadium(v) complexes with a thiadiazole moiety acting as a bridging ligand. Complexes 1 and 3, when dissolved in an appropriate alcohol, underwent substitution of the alkoxo ligand as confirmed by XRPD. The kinetics of reactions in methanolic solutions was qualitatively studied by UV-Vis and ESMS spectrometries. Under the experimental conditions applied, a relatively slow formation of the mononuclear complex [VOL(OMe)] and an even slower formation of the cyclic species 2 were observed, whereas the presence of dinuclear compound [V(2)O(3)(L(cycl))(2)(OMe)(2)] in the reaction mixture could not be detected. PMID:19885541

  18. Development of a Human Immunodeficiency Virus Vector-Based, Single-Cycle Assay for Evaluation of Anti-Integrase Compounds

    PubMed Central

    Bona, Roberta; Andreotti, Mauro; Buffa, Viviana; Leone, Pasqualina; Galluzzo, Clementina Maria; Amici, Roberta; Palmisano, Lucia; Mancini, Maria Grazia; Michelini, Zuleika; Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Pommier, Yves; Marchand, Christophe; Vella, Stefano; Cara, Andrea

    2006-01-01

    Therapeutic strategies aimed at inhibiting human immunodeficiency virus type 1 (HIV-1) replication employ a combination of drugs targeted to two viral enzymes (reverse transcriptase and protease) and to the viral entry/fusion step. However, the high propensity of HIV-1 to develop resistance makes the development of novel compounds targeting different steps of the HIV-1 life cycle essential. Among these, integrase (IN) inhibitors have successfully passed the early phases of clinical development. By preventing integration, IN inhibitors preclude viral replication while allowing production of extrachromosomal forms of viral DNA (E-DNA). Here, we describe an improved and standardized assay aimed at evaluating IN inhibitors by taking advantage of the transcriptional activity of E-DNA produced by HIV-derived vectors in the absence of replication-competent virus. In this context, the use of the firefly luciferase gene as a reporter gene provides a rapid and quantitative measure of viral-vector infectivity, thus making it a safe and cost-effective assay for evaluating novel IN inhibitors. PMID:17005823

  19. Molecular docking of the anticancer bioactive compound proceraside with macromolecules involved in the cell cycle and DNA replication.

    PubMed

    Gurung, A B; Ali, M A; Bhattacharjee, A; AbulFarah, M; Al-Hemaid, F; Abou-Tarboush, F M; Al-Anazi, K M; Al-Anazi, F S M; Lee, J

    2016-01-01

    The bioactive compounds proceraside A, frugoside and calotropin, which were extracted from the root bark of Calotropis procera (Aiton) W.T. Aiton (family Asclepiadaceae), were recently reported to inhibit the growth of inhibition against various human cancer cell lines in vitro. However, their modes of action have not been clearly defined. Therefore, we attempted an in silico approach to gain insights into their binding modes against the following selected molecular targets: CDK-2, CDK-6, topoisomerase I, BCL-2, VEGFR-2, telomere: G-quadruplex, and topoisomerase II. These targets were selected based on their key roles in cancer progression via the regulation of the cell cycle and DNA replication. Molecular-docking analyses revealed that proceraside A was the best docked ligand against all the targets, with the exception of telomere-G: quadruplex. Furthermore, it displayed the lowest binding energies and inhibition constants, and critical hydrogen bonds and hydrophobic interactions with the targets were also revealed. The present study may aid in the identification of possible targets for proceraside A, and might provide a plausible explanation for its proven anti-tumor activities. Moreover, the result of this study may further guide structure-activity relationship studies used to generate more potent target-specific inhibitors. PMID:27173346

  20. The Arctic freshwater cycle during a naturally and an anthropogenically induced warm climate

    NASA Astrophysics Data System (ADS)

    Davies, Frazer J.; Renssen, Hans; Goosse, Hugues

    2014-04-01

    The Arctic freshwater cycle plays an important role in regulating regional and global climate. Current observations suggest that an intensification of the high-northern latitude hydrological cycle has caused a freshening of the Arctic and sub-Arctic seas, increasing the potential of weakening overturning strength in the Nordic seas, and reducing temperatures. It is not known if this freshening is a manifestation of the current anthropogenic warming and if the Arctic freshwater cycle has exhibited similar changes in the past, in particular as a response to naturally induced periods of warming, for example during the mid-Holocene hypsithermal. Thus, we have used an earth model of intermediate complexity, LOVECLIM, to investigate the response of the Arctic freshwater cycle, during two warm periods that evolved under different sets of forcings, the mid-Holocene and the twenty-first century. A combination of proxy reconstructions and modelling studies have shown these two periods to exhibit similar surface temperature anomalies, compared to the pre-industrial period, however, it has yet to be determined if the Arctic freshwater cycle and thus, the transport and redistribution of freshwater to the Arctic and the sub-Arctic seas, during these two warm periods, is comparable. Here we provide an overview that shows that the response of the Arctic freshwater cycle during the first half of the twenty-first century can be interpreted as an `extreme' mid-Holocene hydrological cycle. Whilst for the remainder of the twenty-first century, the Arctic freshwater cycle and the majority of its components will likely transition into what can only be described as truly anthropogenic in nature.

  1. Gypensapogenin H, a novel dammarane-type triterpene induces cell cycle arrest and apoptosis on prostate cancer cells.

    PubMed

    Zhang, Xiao-Shu; Zhao, Chen; Tang, Wei-zhuo; Wu, Xiao-jun; Zhao, Yu-Qing

    2015-12-01

    Gypensapogenin H (GH) is a novel dammarane-type triterpenes obtained from hydrolyzate of total saponins from Gynostemma pentaphyllum and its anti-tumor activity has been studied in previous work. In this study, we report the effects of this compound on human prostate cancer cells (DU145 and 22RV-1). It significantly inhibited proliferation, decreased survival, led to G1 cell cycle arrest and induced apoptosis in both cell lines, while having lesser effect on the growth of normal human gastric mucosa cells (GES-1), embryonic kidney cells (HEK293) and lung fibroblast cells (MRC5). Consistent with these phenotypes, we observed decreased expression of the cell cycle-related proteins cyclinD1, and CDK4, and increased expression of p21 in GH-treated cells. Besides, the anti-apoptotic Bcl-2 protein decreased in a dose-dependent manner, while Bax, cleaved caspase-3 and -9 increased upon GH treatment. Taken together, these results indicated GH exerted promising anticancer activity, and may represent a potential agent for the treatment of prostate cancer. PMID:26514740

  2. Evidence for climate variations induced by the 11-year solar and cosmic rays cycles

    NASA Astrophysics Data System (ADS)

    Bruckman, William; Ramos, Elio

    2010-02-01

    We analyzed data from PSMSL monthly mean sea level seeking correlations between sea level fluctuations and the solar and cosmic rays 11 year cycle. The data reveals decadal variability that could be causally connected to the solar and cosmic rays cycle, since these periodic changes are correlated. It is also found that the solar (cosmic rays) cycle correlates (anti-correlates) with the mean global surface temperature anomaly. A probable explanation of the above correlations is that the solar intensity and cosmic rays variations induce oscillations in the average temperature and precipitation, with corresponding changes in the continental water and snow accumulation. Thus, for instance, a higher than average snow and water over land, and lower temperatures produce oceans thermal contraction and lower mass, implicating lower mean sea level.

  3. The antiangiogenic compound aeroplysinin-1 induces apoptosis in endothelial cells by activating the mitochondrial pathway.

    PubMed

    Martínez-Poveda, Beatriz; Rodríguez-Nieto, Salvador; García-Caballero, Melissa; Medina, Miguel-Ángel; Quesada, Ana R

    2012-09-01

    Aeroplysinin-1 is a brominated metabolite extracted from the marine sponge Aplysina aerophoba that has been previously characterized by our group as a potent antiangiogenic compound in vitro and in vivo. In this work, we provide evidence of a selective induction of apoptosis by aeroplysinin-1 in endothelial cells. Studies on the nuclear morphology of treated cells revealed that aeroplysinin-1 induces chromatin condensation and nuclear fragmentation, and it increases the percentage of cells with sub-diploid DNA content in endothelial, but not in HCT-116, human colon carcinoma and HT-1080 human fibrosarcoma cells. Treatment of endothelial cells with aeroplysinin-1 induces activation of caspases-2, -3, -8 and -9, as well as the cleavage of apoptotic substrates, such as poly (ADP-ribose) polymerase and lamin-A in a caspase-dependent mechanism. Our data indicate a relevant role of the mitochondria in the apoptogenic activity of this compound. The observation that aeroplysinin-1 prevents the phosphorylation of Bad relates to the mitochondria-mediated induction of apoptosis by this compound. PMID:23118719

  4. Chemiluminescence response induced by mesenteric ischaemia/reperfusion: effect of antioxidative compounds ex vivo

    PubMed Central

    Nosál'ová, Viera; Sotníková, Ružena; Drábiková, Katarína; Fialová, Silvia; Košťálová, Daniela; Banášová, Silvia; Navarová, Jana

    2010-01-01

    Ischaemia and reperfusion (I/R) play an important role in human pathophysiology as they occur in many clinical conditions and are associated with high morbidity and mortality. Interruption of blood supply rapidly damages metabolically active tissues. Restoration of blood flow after a period of ischaemia may further worsen cell injury due to an increased formation of free radicals. The aim of our work was to assess macroscopically the extent of intestinal pathological changes caused by mesenteric I/R, and to study free radical production by luminol enhanced chemiluminescence (CL) of ileal samples. In further experiments, the antioxidative activity of the drugs tested was evaluated spectrophotometrically by the use of the DPPH radical. We studied the potential protective ex vivo effect of the plant origin compound arbutin as well as of the pyridoindole stobadine and its derivative SMe1EC2. I/R induced pronounced haemorrhagic intestinal injury accompanied by increase of myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGA) activity. Compared to sham operated (control) rats, there was only a slight increase of CL response after I/R, probably in association with neutrophil increase, indicated by enhanced MPO activity. All compounds significantly reduced the peak values of CL responses of the ileal samples ex vivo, thus reducing the I/R induced increase of free radical production. The antioxidants studied showed a similar inhibitory effect on the CL response influenced by mesenteric I/R. If proved in vivo, these compounds would represent potentially useful therapeutic antioxidants. PMID:21217883

  5. Protective effects of certain pharmaceutical compounds against abrin induced cell death in Jurkat cell line.

    PubMed

    Saxena, Nandita; Rao, P V L; Bhaskar, A S B; Bhutia, Y D

    2014-08-01

    Abrin is a plant glycoprotein toxin from the seeds of Abrus precatorius, and shares the structure and properties with ricin. Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 μg/kg, causing death after accidental and intentional poisoning. It is a potent toxin warfare agent. There are no antidotes available for abrin intoxication. It is becoming increasingly important to develop countermeasures for abrin by developing pre- and post-exposure medical therapy. The present study involves the screening of certain pharmaceutical agents for their potential to counter abrin toxicity in Jurkat T lymphocytes and the probable mechanism of action of the compounds with protective effect. The compounds studied are: Prednisolone, Minocycline, Amifostine, DRDE-07 (amifostine analog), Melatonin, Ebselen, N-Acetyl-l-cysteine (NAC) and Trolox. Among them, only NAC and trolox were found to confer significant protection in Jurkat cells by restoring antioxidant enzymes depleted by abrin treatment. Abrin also shown to increase in stress factor associated proteins SAPK/JNK, c-fos and c-jun levels which were effectively suppressed by NAC and trolox. In addition to this, both compounds significantly inhibit abrin induced inflammation and caspase-3 activity. These data suggest that NAC and trolox may serve as potential candidates for management of abrin-induced poisoning. PMID:24938881

  6. Cell cycle control in isoproterenol-induced murine salivary acinar cell proliferation.

    PubMed

    Zeng, T; Yamamoto, H; Bowen, E; Broverman, R L; Nguyen, K H; Humphreys-Beher, M G

    1996-11-01

    The eukaryotic cell cycle is a summary of a complex network of signal transduction pathways resulting in both DNA replication and cell division. Cyclin-dependent kinases (CDKs) control the cell cycle in all eukaryotes, whereas other proteins, known as cyclins, act as their regulatory subunits. Chronic injection with isoproterenol (ISO) can induce acinar cell proliferation in rodent salivary glands. Cyclins and CDK proteins from control and ISO-treated murine parotid acinar cells were detected by using Western blotting techniques. By comparing the expression of these cell cycle regulatory kinases in the parotid acinar cell transition from a quiescent state to a hypertrophic state, we found rapid increases in the protein levels of all CDKs, cyclin D and proliferating cell nuclear antigen (PCNA). The highest protein levels for CDKs and cyclins appeared at about 72 hr of ISO stimulation and were coincident with the highest rate of increase in gland wet weight. After 72 hr, the increase of both cell cycle protein and gland wet weight began to subside. By using a co-immunoprecipitation method, the following cell cycle regulators (CDK-cyclin complexes) were detected, CDK4-cyclin D, CDK2-cyclin E, CDK2-cyclin A, and cdc2-cyclin B, along with an increase in kinase activity over control untreated animals. Additionally, we detected significant decreases in the newly isolated CDK inhibitor (CKI) p27kip but not Wee 1 kinase. The increased levels of CKI correlated with a decrease in kinase activity of CDK/cyclin complexes by 144 hr of chronic isoproterenol treatment. Our data suggest that the holoenzymes for cell cycle control (cyclin-CDK complexes) function as a final regulatory mechanism leading to salivary gland acinar cell proliferation. The gradual decline in protein levels of the CDKs and cyclins after 3 days of chronic treatment further indicates that ISO-induced proliferation of parotid acinar cells is self-limiting and non-tumorigenic. PMID:9375366

  7. Citral inhibits cell proliferation and induces apoptosis and cell cycle arrest in MCF-7 cells.

    PubMed

    Chaouki, Wahid; Leger, David Y; Liagre, Bertrand; Beneytout, Jean-Louis; Hmamouchi, Mohamed

    2009-10-01

    Many natural components of plants extract are studied for their beneficial effects on health and particularly on carcinogenesis chemoprevention. In this study, we investigated the effect of citral (3,7-dimethyl-2,6-octadienal), a key component of essential oils extracted from several herbal plants, on the proliferation rate, cell cycle distribution, and apoptosis of the human breast cancer cell line MCF-7. The effects of this compound were also tested on cyclo-oxygenase activity. Citral treatment caused inhibition of MCF-7 cell growth (IC(50)-48 h: 18 x 10(-5)m), with a cycle arrest in G(2)/M phase and apoptosis induction. Moreover, we observed a decrease in prostaglandin E(2) synthesis 48 h after citral treatment. These findings suggest that citral has a potential chemopreventive effect. PMID:19656204

  8. A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells.

    PubMed

    Shahabuddin, M S; Nambiar, Mridula; Choudhary, Bibha; Advirao, Gopal M; Raghavan, Sathees C

    2010-02-01

    DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics. PMID:19142583

  9. PEA15 Regulates the DNA Damage-Induced Cell Cycle Checkpoint and Oncogene-Directed Transformation

    PubMed Central

    Nagarajan, Arvindhan; Dogra, Shaillay Kumar; Liu, Alex Y.; Green, Michael R.

    2014-01-01

    Regulation of the DNA damage response and cell cycle progression is critical for maintaining genome integrity. Here, we report that in response to DNA damage, COPS5 deubiquitinates and stabilizes PEA15 in an ATM kinase-dependent manner. PEA15 expression oscillates throughout the cell cycle, and the loss of PEA15 accelerates cell cycle progression by activating CDK6 expression via the c-JUN transcription factor. Cells lacking PEA15 exhibit a DNA damage-induced G2/M checkpoint defect due to increased CDC25C activity and, consequentially, higher cyclin-dependent kinase 1 (CDK1)/cyclin B activity, and accordingly they have an increased rate of spontaneous mutagenesis. We find that oncogenic RAS inhibits PEA15 expression and that ectopic PEA15 expression blocks RAS-mediated transformation, which can be partially rescued by ectopic expression of CDK6. Finally, we show that PEA15 expression is downregulated in colon, breast, and lung cancer samples. Collectively, our results demonstrate that tumor suppressor PEA15 is a regulator of genome integrity and is an integral component of the DNA damage response pathway that regulates cell cycle progression, the DNA-damage-induced G2/M checkpoint, and cellular transformation. PMID:24710276

  10. Suppression of the antiferroelectric phase during polarization cycling of an induced ferroelectric phase

    SciTech Connect

    Liu, Xiaoming; Tan, Xiaoli

    2015-08-17

    The ceramic Pb{sub 0.99}Nb{sub 0.02}[(Zr{sub 0.57}Sn{sub 0.43}){sub 0.92}Ti{sub 0.08}]{sub 0.98}O{sub 3} can exist in either an antiferroelectric or a ferroelectric phase at room temperature, depending on the thermal and electrical history. The antiferroelectric phase can be partially recovered from the induced ferroelectric phase when the applied field reverses polarity. Therefore, polarization cycling of the ferroelectric phase in the ceramic under bipolar fields at room temperature is accompanied with repeated phase transitions. In this letter, the stability of the recovered antiferroelectric phase upon electrical cycling of the ceramic is investigated. Ex-situ X-ray diffraction reveals that bipolar cycling suppresses the antiferroelectric phase; this is indirectly supported by piezoelectric coefficient d{sub 33} measurements. It is speculated that the accumulated charged point defects during polarization cycling stabilize the polar ferroelectric phase. The findings presented are important to the fundamental studies of electric fatigue and field-induced phase transitions in ferroelectrics.

  11. PEA15 regulates the DNA damage-induced cell cycle checkpoint and oncogene-directed transformation.

    PubMed

    Nagarajan, Arvindhan; Dogra, Shaillay Kumar; Liu, Alex Y; Green, Michael R; Wajapeyee, Narendra

    2014-06-01

    Regulation of the DNA damage response and cell cycle progression is critical for maintaining genome integrity. Here, we report that in response to DNA damage, COPS5 deubiquitinates and stabilizes PEA15 in an ATM kinase-dependent manner. PEA15 expression oscillates throughout the cell cycle, and the loss of PEA15 accelerates cell cycle progression by activating CDK6 expression via the c-JUN transcription factor. Cells lacking PEA15 exhibit a DNA damage-induced G2/M checkpoint defect due to increased CDC25C activity and, consequentially, higher cyclin-dependent kinase 1 (CDK1)/cyclin B activity, and accordingly they have an increased rate of spontaneous mutagenesis. We find that oncogenic RAS inhibits PEA15 expression and that ectopic PEA15 expression blocks RAS-mediated transformation, which can be partially rescued by ectopic expression of CDK6. Finally, we show that PEA15 expression is downregulated in colon, breast, and lung cancer samples. Collectively, our results demonstrate that tumor suppressor PEA15 is a regulator of genome integrity and is an integral component of the DNA damage response pathway that regulates cell cycle progression, the DNA-damage-induced G2/M checkpoint, and cellular transformation. PMID:24710276

  12. Hydrogen cycling-induced phase segregation in AB{sub 5}-type intermetallics

    SciTech Connect

    Mordkovich, V.Z.

    1998-12-31

    A study of hydrogen cycling-induced phase segregation in AB{sub 5}-type intermetallics is presented. Influence of temperature for the alloy compositions YNi{sub 4}Al, LaNi{sub 5}, Ce{sub 0.5}La{sub 0.5}Ni{sub 5} and Ce{sub 0.7}La{sub 0.3}Ni{sub 5} is shown. Morphology of the nanostructured particles formed is studied and discussed.

  13. Isolation and characterization of wound-induced compounds from the leaves of Citrus hassaku.

    PubMed

    Asai, Tomonori; Matsukawa, Tetsuya; Ishihara, Atsushi; Kajiyama, Shin'ichiro

    2016-08-01

    Citrus plants are world widely cultivated as horticultural tree crops, and nowadays their pharmacological activities have been well studied. Since research of defense responses in citrus plants have been mainly focused on the post-harvested fruits because of their commercial importance, defense mechanisms during their developmental stages have not been well understood. In the present study, two wound-induced compounds were isolated from leaves of Citrus hassaku, and their structures were elucidated by high-resolution electron spray ionization mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) analyses. One of these compounds was identified as a known flavanone, hesperetin. The other was characterized as a novel furofuran lignan, and was named 'biscitrusnin-A'. Their antimicrobial activities were also evaluated. PMID:26852089

  14. Mast cell degranulation mediates compound 48/80-induced hyperalgesia in mice

    PubMed Central

    Chatterjea, Devavani; Wetzel, Abigail; Mack, Madison; Engblom, Camilla; Allen, Juliann; Mora-Solano, Carolina; Paredes, Luisa; Balsells, Evelyn; Martinov, Tijana

    2012-01-01

    Mast cells mediate allergies, hypersensitivities, host defense, and venom neutralization. An area of recent interest is the contribution of mast cells to inflammatory pain. Here we found that specific, local activation of mast cells produced plantar hyperalgesia in mice. Basic secretagogue compound 48/80 induced plantar mast cell degranulation accompanied by thermal hyperalgesia, tissue edema, and neutrophil influx in the hindpaws of ND4 Swiss mice. Blocking mast cell degranulation, neutrophil extravasation, and histamine signaling abrogated these responses. Compound 48/80 also produced edema, pain, and neutrophil influx in WT C57BL/6 but not in genetically mast cell-deficient C57BL/6-KitW-sh/W-sh mice. These responses were restored following plantar reconstitution with bone marrow-derived cultured mast cells. PMID:22828511

  15. Effects of compound D600 (methoxyverapamil) on drug-induced contractions of isolated dog uterine muscle.

    PubMed

    Calixto, J B; Antônio, A

    1986-01-01

    The contractile responses of the isolated dog uterus to acetylcholine (Ach), oxytocin (Ot), histamine (Hist) and barium chloride (Ba2+) were non-competitively blocked by compound D600. This compound was significantly more potent against Ba2+-induced contractions. Increasing the calcium (Ca2+) concentration from 0.2 to 2.5 mM reverted the inhibitory effects of D600 against Ach, Ot, Hist and 1 mM Ba2+. The blockade produced by D600 against 30 mM Ba2+ was not reversed by increasing the Ca2+ concentration. In high K+-depolarizing solution, D600 produced a parallel and concentration-dependent displacement to the right to the concentration-response curves of both Ca2+ and Ba2+. The Schild plot yielded similar pA2 values for D600 against Ca2+ and Ba2+. PMID:3699446

  16. Pfaffosidic Fraction from Hebanthe paniculata Induces Cell Cycle Arrest and Caspase-3-Induced Apoptosis in HepG2 Cells

    PubMed Central

    da Silva, Tereza Cristina; Cogliati, Bruno; Latorre, Andréia Oliveira; Akisue, Gokithi; Nagamine, Márcia Kazumi; Haraguchi, Mitsue; Hansen, Daiane; Sanches, Daniel Soares; Dagli, Maria Lúcia Zaidan

    2015-01-01

    Hebanthe paniculata roots (formerly Pfaffia paniculata and popularly known as Brazilian ginseng) show antineoplastic, chemopreventive, and antiproliferative properties. Functional properties of these roots and their extracts are usually attributed to the pfaffosidic fraction, which is composed mainly by pfaffosides A–F. However, the therapeutic potential of this fraction in cancer cells is not yet entirely understood. This study aimed to analyze the antitumoral effects of the purified pfaffosidic fraction or saponinic fraction on the human hepatocellular carcinoma HepG2 cell line. Cellular viability, proliferation, and apoptosis were evaluated, respectively, by MTT assay, BrdU incorporation, activated caspase-3 immunocytochemistry, and DNA fragmentation assay. Cell cycle was analyzed by flow cytometry and the cell cycle-related proteins were analyzed by quantitative PCR and Western blot. The cells exposed to pfaffosidic fraction had reduced viability and cellular growth, induced G2/M at 48 h or S at 72 h arrest, and increased sub-G1 cell population via cyclin E downregulation, p27KIP1 overexpression, and caspase-3-induced apoptosis, without affecting the DNA integrity. Antitumoral effects of pfaffosidic fraction from H. paniculata in HepG2 cells originated by multimechanisms of action might be associated with cell cycle arrest in the S phase, by CDK2 and cyclin E downregulation and p27KIP1 overexpression, besides induction of apoptosis through caspase-3 activation. PMID:26075002

  17. Plant compounds that induce polychlorinated biphenyl biodegradation by Arthrobacter sp. strain B1B.

    PubMed Central

    Gilbert, E S; Crowley, D E

    1997-01-01

    Plant compounds that induced Arthrobacter sp. strain B1B to cometabolize polychlorinated biphenyls (PCBs) were identified by a screening assay based on the formation of a 4,4'-dichlorobiphenyl ring fission product. A chemical component of spearmint (Mentha spicata), l-carvone, induced Arthrobacter sp. strain B1B to cometabolize Aroclor 1242, resulting in significant degradation of 26 peaks in the mixture, including selected tetra- and pentachlorobiphenyls. Evidence for PCB biodegradation included peak disappearance, formation of a phenylhexdienoate ring fission product, and chlorobenzoate accumulation in the culture supernatant. Carvone was not utilized as a growth substrate and was toxic at concentrations of greater than 500 mg liter-1. Several compounds structurally related to l-carvone, including limonene, p-cymene, and isoprene, also induced cometabolism of PCBs by Arthrobacter sp. strain B1B. A structure-activity analysis showed that chemicals with an unsaturated p-menthane structural motif promoted the strongest cometabolism activity. These data suggest that certain plant-derived terpenoids may be useful for promoting enhanced rates of PCB biodegradation by soil bacteria. PMID:9143124

  18. Antiproliferative and cell apoptosis-inducing activities of compounds from Buddleja davidii in Mgc-803 cells

    PubMed Central

    2012-01-01

    Background Buddleja davidii is widely distributed in the southwestern region of China. We have undertaken a systematic analysis of B. davidii as a Chinese traditional medicine with anticancer activity by isolating natural products for their activity against the human gastric cancer cell line Mgc-803 and the human breast cancer cell line Bcap-37. Results Ten compounds were extracted and isolated from B. davidii, among which colchicine was identified in B. davidii for the first time. The inhibitory activities of these compounds were investigated in Mgc-803, Bcap-37 cells in vitro by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and the results showed that luteolin and colchicine had potent inhibitory activities against the growth of Mgc-803 cells. Subsequent fluorescence staining and flow cytometry analysis indicated that these two compounds could induce apoptosis in Mgc-803 cells. The results also showed that the percentages of early apoptotic cells (Annexin V+/PI-, where PI is propidium iodide) and late apoptotic cells (Annexin V+/PI+) increased in a dose- and time-dependent manner. After 36 h of incubation with luteolin at 20 μM, the percentages of cells were approximately 15.4% in early apoptosis and 43.7% in late apoptosis; after 36 h of incubation with colchicine at 20 μM, the corresponding values were 7.7% and 35.2%, respectively. Conclusions Colchicine and luteolin from B. davidii have potential applications as adjuvant therapies for treating human carcinoma cells. These compounds could also induce apoptosis in tumor cells. PMID:22938042

  19. Compound specific amino acid δ15N in marine sediments: A new approach for studies of the marine nitrogen cycle

    NASA Astrophysics Data System (ADS)

    Batista, Fabian C.; Ravelo, A. Christina; Crusius, John; Casso, Michael A.; McCarthy, Matthew D.

    2014-10-01

    The nitrogen (N) isotopic composition (δ15N) of bulk sedimentary N (δ15Nbulk) is a common tool for studying past biogeochemical cycling in the paleoceanographic record. Empirical evidence suggests that natural fluctuations in the δ15N of surface nutrient N are reflected in the δ15N of exported planktonic biomass and in sedimentary δ15Nbulk. However, δ15Nbulk is an analysis of total combustible sedimentary N, and therefore also includes mixtures of N sources and/or selective removal or preservation of N-containing compounds. Compound-specific nitrogen isotope analyses of individual amino acids (δ15NAA) are novel measurements with the potential to decouple δ15N changes in nutrient N from trophic effects, two main processes that can influence δ15Nbulk records. As a proof of concept study to examine how δ15NAA can be applied in marine sedimentary systems, we compare the δ15NAA signatures of surface and sinking POM sources with shallow surface sediments from the Santa Barbara Basin, a sub-oxic depositional environmental that exhibits excellent preservation of sedimentary organic matter. Our results demonstrate that δ15NAA signatures of both planktonic biomass and sinking POM are well preserved in such surface sediments. However, we also observed an unexpected inverse correlation between δ15N value of phenylalanine (δ15NPhe; the best AA proxy for N isotopic value at the base of the food web) and calculated trophic position. We used a simple N isotope mass balance model to confirm that over long time scales, δ15NPhe values should in fact be directly dependent on shifts in ecosystem trophic position. While this result may appear incongruent with current applications of δ15NAA in food webs, it is consistent with expectations that paleoarchives will integrate N dynamics over much longer timescales. We therefore propose that for paleoceanographic applications, key δ15NAA parameters are ecosystem trophic position, which determines relative partitioning of 15N

  20. Deciphering Complex Carbon Cycle Changes Across the K-Pg Boundary Using Compound-Specific Carbon Isotopic Analyses

    NASA Astrophysics Data System (ADS)

    Pancost, R. D.; Taylor, K. W.; Hollis, C. J.; Crouch, E. M.

    2014-12-01

    The consequences of the Cretaceous-Paleogene (K/Pg) boundary event on the Earth system have been the subject of much scrutiny. Postulated climate events include a brief (10 - 2000 yr) period of global cooling induced by sulphate aerosols (the so-called 'impact winter'), an interval of warming caused by impact-induced CO2release, as well as longer-term climatic oscillations during the subsequent 1 to 3Myr. Associated with these were putative changes in the biogeochemical cycle, manifested as carbon isotope excursions on both short- and long-term timescales. In this study we develop new biomarker-based climate and biogeochemical records for the mid-Waipara River and Branch Stream sections, NZ. At Branch Stream, a pronounced negative (ca 6 to 8 permil) carbon isotope excursion occurs at the K/Pg; the excursion is recorded by higher plant biomarkers, consistent with some terrestrial records and suggesting that the immediate aftermath of the K/Pg boundary event was characterised by the massive release of 13C-depleted reduced carbon into the ocean-atmosphere reservoir. Mixing across the K/Pg boundary at the Waipara section precludes a similar high-resolution investigation. Lower-resolution, longer-term records, however, also reveal a negative carbon istope excursion documented by both algal and higher plant biomarkers. This event appears to be distinct from that recorded at Branch Stream, being of lower magnitude and longer duration. It coincided with a transient terrestrial and marine warming and appears to have lasted at least 100 kyr and perhaps longer. We argue that this protracted negative CIE reflects a secondary and longer-term consequence of the K/Pg on the global carbon cycle. There is little evidence for an algal extinction as a range of C27 to C30 sterols continued to be deposited throughout the entire section, but changes in GDGT distributions do suggest a change in carbon export dynamics which could have impacted burial of 13C-depleted marine organic matter

  1. Small Compound 6-O-Angeloylplenolin Induces Mitotic Arrest and Exhibits Therapeutic Potentials in Multiple Myeloma

    PubMed Central

    Liu, Ying; Chen, Xiao-Qin; Liang, Heng-Xing; Zhang, Feng-Xiang; Zhang, Bo; Jin, Jie; Chen, Yong-Long; Cheng, Yong-Xian; Zhou, Guang-Biao

    2011-01-01

    Background Multiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells. Methodology/Principal Findings MM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal cells (BMSCs) were treated with 6-OAP. The effects of 6-OAP plus other drugs on MM.1S cells were evaluated. The in vivo therapeutic efficacy and pharmacokinetic features of 6-OAP were tested in nude mice bearing U266 cells and Sprague-Dawley rats, respectively. We found that 6-OAP suppressed the proliferation of dexamethasone-sensitive and dexamethasone-resistant cell lines and primary CD138+ MM cells. 6-OAP caused mitotic arrest, accompanied by activation of spindle assembly checkpoint and blockage of ubiquitiniation and subsequent proteasomal degradation of cyclin B1. Combined use of 6-OAP and bortezomib induced potentiated cytotoxicity with inactivation of ERK1/2 and activation of JNK1/2 and Casp-8/-3. 6-OAP overcame the protective effects of IL-6 and IGF-I on MM cells through inhibition of Jak2/Stat3 and Akt, respectively. 6-OAP inhibited BMSCs-facilitated MM cell expansion and TNF-α-induced NF-κB signal. Moreover, 6-OAP exhibited potent anti-MM activity in nude mice and favorable pharmacokinetics in rats. Conclusions/Significance These results indicate that 6-OAP is a new cell cycle inhibitor which shows therapeutic potentials for MM. PMID:21755010

  2. A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation.

    PubMed

    Moncunill-Massaguer, Cristina; Saura-Esteller, José; Pérez-Perarnau, Alba; Palmeri, Claudia Mariela; Núñez-Vázquez, Sonia; Cosialls, Ana M; González-Gironès, Diana M; Pomares, Helena; Korwitz, Anne; Preciado, Sara; Albericio, Fernando; Lavilla, Rodolfo; Pons, Gabriel; Langer, Thomas; Iglesias-Serret, Daniel; Gil, Joan

    2015-12-01

    We previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the regulation of several cellular processes, including apoptosis. Here we demonstrate that fluorizoline-induced apoptosis is mediated by PHBs, as cells depleted of these proteins are highly resistant to fluorizoline treatment. In addition, BAX and BAK are necessary for fluorizoline-induced cytotoxic effects, thereby proving that apoptosis occurs through the intrinsic pathway. Expression analysis revealed that fluorizoline induced the upregulation of Noxa and Bim mRNA levels, which was not observed in PHB-depleted MEFs. Finally, Noxa(-/-)/Bim(-/-) MEFs and NOXA-downregulated HeLa cells were resistant to fluorizoline-induced apoptosis. All together, these findings show that fluorizoline requires PHBs to execute the mitochondrial apoptotic pathway. PMID:26497683

  3. A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation

    PubMed Central

    Moncunill-Massaguer, Cristina; Saura-Esteller, José; Pérez-Perarnau, Alba; Palmeri, Claudia Mariela; Núñez-Vázquez, Sonia; Cosialls, Ana M.; González-Gironès, Diana M.; Pomares, Helena; Korwitz, Anne; Preciado, Sara; Albericio, Fernando; Lavilla, Rodolfo; Pons, Gabriel; Langer, Thomas; Iglesias-Serret, Daniel; Gil, Joan

    2015-01-01

    We previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the regulation of several cellular processes, including apoptosis. Here we demonstrate that fluorizoline-induced apoptosis is mediated by PHBs, as cells depleted of these proteins are highly resistant to fluorizoline treatment. In addition, BAX and BAK are necessary for fluorizoline-induced cytotoxic effects, thereby proving that apoptosis occurs through the intrinsic pathway. Expression analysis revealed that fluorizoline induced the upregulation of Noxa and Bim mRNA levels, which was not observed in PHB-depleted MEFs. Finally, Noxa−/−/Bim−/− MEFs and NOXA-downregulated HeLa cells were resistant to fluorizoline-induced apoptosis. All together, these findings show that fluorizoline requires PHBs to execute the mitochondrial apoptotic pathway. PMID:26497683

  4. AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells.

    PubMed

    Carpi, Sara; Fogli, Stefano; Romanini, Antonella; Pellegrino, Mario; Adinolfi, Barbara; Podestà, Adriano; Costa, Barbara; Da Pozzo, Eleonora; Martini, Claudia; Breschi, Maria Cristina; Nieri, Paola

    2015-08-01

    Human cutaneous melanoma is an aggressive and chemotherapy-resistant type of cancer. AM251 is a cannabinoid type 1 (CB1) receptor antagonist/inverse agonist with off-target antitumor activity against pancreatic and colon cancer cells. The current study aimed to characterize the in-vitro antimelanoma activity of AM251. The BRAF V600E mutant melanoma cell line, A375, was used as an in-vitro model system. Characterization tools included a cell viability assay, nuclear morphology assessment, gene expression, western blot, flow cytometry with Annexin V-FITC/7-AAD double staining, cell cycle analyses, and measurements of changes in intracellular cAMP and calcium concentrations. AM251 exerted a marked cytotoxic effect against A375 human melanoma cells with potency comparable with that observed for cisplatin without significant changes in the human dermal fibroblasts viability. AM251, at a concentration that approximates the IC50, downregulated genes encoding antiapoptotic proteins (BCL2 and survivin) and increased transcription levels of proapoptotic BAX, induced alteration of Annexin V reactivity, DNA fragmentation, chromatin condensation in the cell nuclei, and G2/M phase arrest.AM251 also induced a 40% increase in the basal cAMP levels, but it did not affect intracellular calcium concentrations. The involvement of GPR55, TRPA1, and COX-2 in the AM251 mechanism of action was excluded. The combination of AM251 with celecoxib produced a synergistic antitumor activity, although the mechanism underlying this effect remains to be elucidated. This study provides the first evidence of a proapoptotic effect and G2/M cell cycle arrest of AM251 on A375 cells. This compound may be a potential prototype for the development of promising diarylpyrazole derivatives to be evaluated in human cutaneous melanoma. PMID:25974027

  5. Generalized Electron Counting in Determination of Metal-Induced Reconstruction of Compound Semiconductor Surfaces

    SciTech Connect

    Zhang, Lixin; Wang, E. G.; Xue, Qi-Kun; Zhang, S. B.; Zhang, Zhenyu

    2006-01-01

    Based on theoretical analysis, first-principles calculations, and experimental observations, we establish a generic guiding principle, embodied in generalized electron counting (GEC), that governs the surface reconstruction of compound semiconductors induced by different metal adsorbates. Within the GEC model, the adsorbates serve as an electron bath, donating or accepting the right number of electrons as the host surface chooses a specific reconstruction that obeys the classic electron-counting model. The predictive power of the GEC model is illustrated for a wide range of metal adsorbates.

  6. A Stress-Induced Small RNA Modulates Alpha-Rhizobial Cell Cycle Progression

    PubMed Central

    Robledo, Marta; Frage, Benjamin; Wright, Patrick R.; Becker, Anke

    2015-01-01

    Mechanisms adjusting replication initiation and cell cycle progression in response to environmental conditions are crucial for microbial survival. Functional characterization of the trans-encoded small non-coding RNA (trans-sRNA) EcpR1 in the plant-symbiotic alpha-proteobacterium Sinorhizobium meliloti revealed a role of this class of riboregulators in modulation of cell cycle regulation. EcpR1 is broadly conserved in at least five families of the Rhizobiales and is predicted to form a stable structure with two defined stem-loop domains. In S. meliloti, this trans-sRNA is encoded downstream of the divK-pleD operon. ecpR1 belongs to the stringent response regulon, and its expression was induced by various stress factors and in stationary phase. Induced EcpR1 overproduction led to cell elongation and increased DNA content, while deletion of ecpR1 resulted in reduced competitiveness. Computationally predicted EcpR1 targets were enriched with cell cycle-related mRNAs. Post-transcriptional repression of the cell cycle key regulatory genes gcrA and dnaA mediated by mRNA base-pairing with the strongly conserved loop 1 of EcpR1 was experimentally confirmed by two-plasmid differential gene expression assays and compensatory changes in sRNA and mRNA. Evidence is presented for EcpR1 promoting RNase E-dependent degradation of the dnaA mRNA. We propose that EcpR1 contributes to modulation of cell cycle regulation under detrimental conditions. PMID:25923724

  7. Sonoporation induces apoptosis and cell cycle arrest in human promyelocytic leukemia cells.

    PubMed

    Zhong, Wenjing; Sit, Wai Hung; Wan, Jennifer M F; Yu, Alfred C H

    2011-12-01

    Despite being a transient biophysical phenomenon, sonoporation is known to disturb the homeostasis of living cells. This work presents new evidence on how sonoporation may lead to antiproliferation effects including cell-cycle arrest and apoptosis through disrupting various cell signaling pathways. Our findings were obtained from sonoporation experiments conducted on HL-60 human promyelocytic leukemia cells (with 1% v/v microbubbles; 1 MHz ultrasound; 0.3 or 0.5MPa peak negative pressure; 10% duty cycle; 1 kHz pulse repetition frequency; 1 min exposure period). Membrane resealing in these sonoporated cells was first verified using scanning electron microscopy. Time-lapse flow cytometry analysis of cellular deoxyribonucleic acid (DNA) contents was then performed at four post-sonoporation time points (4 h, 8 h, 12 h and 24 h). Results indicate that an increasing trend in the apoptotic cell population can be observed for at least 12 h after sonoporation, whilst viable sonoporated cells are found to temporarily accumulate in the G(2)/M (gap-2/mitosis) phase of the cell cycle. Further analysis using western blotting reveals that sonoporation-induced apoptosis involves cleavage of poly adenosine diphosphate ribose polymerase (PARP) proteins: a pro-apoptotic hallmark related to loss of DNA repair functionality. Also, mitochondrial signaling seems to have taken part in triggering this cellular event as the expression of two complementary regulators for mitochondrial release of pro-apoptotic molecules, Bcl-2 (B-cell lymphoma 2) and Bax (Bcl-2-associated X), are seen to be imbalanced in sonoporated cells. Furthermore, sonoporation is found to induce cell-cycle arrest through perturbing the expression of various cyclin and Cdk (cyclin-dependent kinase) checkpoint proteins that play an enabling role in cell-cycle progression. These bioeffects should be taken into account when using sonoporation for therapeutic purposes. PMID:22033133

  8. Novel hydrogen sulfide-releasing compound, S-propargyl-cysteine, prevents STZ-induced diabetic nephropathy.

    PubMed

    Qian, Xin; Li, Xinghui; Ma, Fenfen; Luo, Shanshan; Ge, Ruowen; Zhu, Yizhun

    2016-05-13

    In this work, we demonstrated for the first time that S-propargyl-cysteine (SPRC, also named as ZYZ-802), a novel hydrogen sulfide (H2S)-releasing compound, had renoprotective effects on streptozotocin (STZ)-induced diabetic kidney injury. SPRC treatment significantly reduced the level of creatinine, kidney to body weight ratio and in particular, markedly decreased 24-h urine microalbuminuria excretion. SPRC suppressed the mRNA expression of fibronectin and type IV collagen. In vitro, SPRC inhibited mesangial cells over-proliferation and hypertrophy induced by high glucose. Additionally, SPRC attenuated inflammation in diabetic kidneys. SPRC also reduced transforming growth factor β1 (TGF-β1) signaling and expression of phosphorylated Smad3 (p-Smad3) pathway. Moreover, SPRC inhibited phosphorylation of ERK, p38 protein. Taken together, SPRC was demonstrated to be a potential therapeutic candidate to suppress diabetic nephropathy. PMID:27055593

  9. Pressure-induced superconductivity in topological parent compound Bi2Te3

    SciTech Connect

    Zhang, J. L.; Zhang, S. J.; Weng, H. M.; Zhang, W.; Yang, L. X.; Liu, Q. Q.; Feng, S. M.; Wang, X. C.; Yu, R. C.; Cao, L. Z.; Wang, L.; Yang, W. G.; Liu, H. Z.; Zhao, W. Y.; Zhang, S. C.; Dai, X.; Fang, Z.; Jin, C. Q.

    2011-01-04

    We report a successful observation of pressure-induced superconductivity in a topological compound Bi₂Te₃ with Tc of ~3 K between 3 to 6 GPa. The combined high-pressure structure investigations with synchrotron radiation indicated that the superconductivity occurred at the ambient phase without crystal structure phase transition. The Hall effects measurements indicated the hole-type carrier in the pressure-induced superconducting Bi₂Te₃ single crystal. Consequently, the first-principles calculations based on the structural data obtained by the Rietveld refinement of X-ray diffraction patterns at high pressure showed that the electronic structure under pressure remained topologically nontrivial. The results suggested that topological superconductivity can be realized in Bi₂Te₃ due to the proximity effect between superconducting bulk states and Dirac-type surface states. We also discuss the possibility that the bulk state could be a topological superconductor.

  10. Novel Pactamycin Analogs Induce p53 Dependent Cell-Cycle Arrest at S-Phase in Human Head and Neck Squamous Cell Carcinoma (HNSCC) Cells

    PubMed Central

    Guha, Gunjan; Liang, Xiaobo; Kulesz-Martin, Molly F.; Mahmud, Taifo; Indra, Arup Kumar; Ganguli-Indra, Gitali

    2015-01-01

    Pactamycin, although putatively touted as a potent antitumor agent, has never been used as an anticancer drug due to its high cytotoxicity. In this study, we characterized the effects of two novel biosynthetically engineered analogs of pactamycin, de-6MSA-7-demethyl-7-deoxypactamycin (TM-025) and 7-demethyl-7-deoxypactamycin (TM-026), in head and neck squamous cell carcinoma (HNSCC) cell lines SCC25 and SCC104. Both TM-025 and TM-026 exert growth inhibitory effects on HNSCC cells by inhibiting cell proliferation. Interestingly, unlike their parent compound pactamycin, the analogs do not inhibit synthesis of nascent protein in a cell-based assay. Furthermore, they do not induce apoptosis or autophagy in a dose- or a time-dependent manner, but induce mild senescence in the tested cell lines. Cell cycle analysis demonstrated that both analogs significantly induce cell cycle arrest of the HNSCC cells at S-phase resulting in reduced accumulation of G2/M-phase cells. The pactamycin analogs induce expression of cell cycle regulatory proteins including master regulator p53, its downstream target p21Cip1/WAF1, p27kip21, p19, cyclin E, total and phospho Cdc2 (Tyr15) and Cdc25C. Besides, the analogs mildly reduce cyclin D1 expression without affecting expression of cyclin B, Cdk2 and Cdk4. Specific inhibition of p53 by pifithrin-α reduces the percentage of cells accumulated in S-phase, suggesting contribution of p53 to S-phase increase. Altogether, our results demonstrate that Pactamycin analogs TM-025 and TM-026 induce senescence and inhibit proliferation of HNSCC cells via accumulation in S-phase through possible contribution of p53. The two PCT analogs can be widely used as research tools for cell cycle inhibition studies in proliferating cancer cells with specific mechanisms of action. PMID:25938491

  11. The diurnal and solar cycle variation of the charge exchange induced hydrogen escape flux

    NASA Technical Reports Server (NTRS)

    Maher, L. J.; Tinsley, B. A.

    1978-01-01

    On the basis of ion temperature and density data at specific points and times in June 1969 provided by the OGO 6 satellite, and altitude profiles of the ion and electron temperature and concentration provided by the Arecibo radar facility over the period February 1972-April 1974, the diurnal and solar cycle variation of the charge-exchange-induced hydrogen escape flux was investigated. It was calculated that for low to moderate solar activity at Arecibo, the diurnal ratio of the maximum-to-minimum charge-exchange-induced hydrogen escape flux was approximately 6 with a peak around noon and a minimum somewhere between 0100 and 0300 h LT. This study of a limited amount of OGO 6 and Arecibo data seems to indicate that the charge-exchange-induced hydrogen escape flux increases as the F(10.7) flux increases for low to moderate solar activity.

  12. NCI in vitro and in silico anticancer screen, cell cycle pertubation and apoptosis-inducing potential of new acylated, benzylidene and isopropylidene derivatives of andrographolide.

    PubMed

    Wong, Charng Choon; Sagineedu, Sreenivasa Rao; Sumon, Shariful Hasan; Sidik, Shiran Mohamad; Phillips, Roger; Lajis, Nordin H; Stanslas, Johnson

    2014-09-01

    Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate. PMID:25168151

  13. Springs-neaps cycles in daily total seabed light: Daylength-induced changes

    NASA Astrophysics Data System (ADS)

    Roberts, E. M.; Bowers, D. G.; Davies, A. J.

    2014-04-01

    In shallow, tidal seas, daily total seabed light is determined largely by the interaction of the solar elevation cycle, the tidal cycle in water depth, and any temporal variability in turbidity. Since tidal range, times of low water, and often turbidity vary in regular ways over the springs-neaps cycle, daily total seabed light exhibits cycles of the same periodicity. Corresponding cycles are likely to be induced in the daily total primary production of benthic algae and plants, particularly those light-limited specimens occupying the lower reaches of a sub-tidal population. Consequently, this effect is an important control on the growth patterns, depth distribution and survival of, for example, macroalgal forests and seagrass meadows. Seasonal changes in daylength exert an important additional control on these cycles, as they alter the fraction of the tidal and turbidity cycles occurring within daylight hours. Bowers et al. (1997) modelled this phenomenon numerically and predicted that for a site with low water at about midday and midnight at neaps tides, 6 am and 6 pm at springs, daily total seabed light peaks at neaps in winter, but the ‘sense' of the cycle ‘switches' so that it peaks at springs in summer - the longer daylength permits the morning and evening low water springs to contribute substantially to the daily total. Observations for such a site in North Wales (UK), presented in this paper, show that no such ‘switch' occurs, and neaps tides host the largest daily totals throughout the year. The predicted ‘switch' is not observed because turbidity increases generally at spring tides, and specifically at low water springs, both of which were not accounted for in the model. Observations at a second site in Brittany (France), diametrically opposite in terms of the times of low water at neaps and at springs, indicate a peak at springs throughout the year. Analytical tools are developed to calculate the percentage of daily total sea surface irradiance

  14. SPARC expression induces cell cycle arrest via STAT3 signaling pathway in medulloblastoma cells

    SciTech Connect

    Chetty, Chandramu; Dontula, Ranadheer; Gujrati, Meena; Lakka, Sajani S.

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Ectopic expression of SPARC impaired cell proliferation in medulloblastoma cells. Black-Right-Pointing-Pointer SPARC expression induces STAT3 mediated cell cycle arrest in medulloblastoma cells. Black-Right-Pointing-Pointer SPARC expression significantly inhibited pre-established tumor growth in nude-mice. -- Abstract: Dynamic cell interaction with ECM components has profound influence in cancer progression. SPARC is a component of the ECM, impairs the proliferation of different cell types and modulates tumor cell aggressive features. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we demonstrate that expression of SPARC inhibits medulloblastoma cell proliferation. MTT assay indicated a dose-dependent reduction in tumor cell proliferation in adenoviral mediated expression of SPARC full length cDNA (Ad-DsRed-SP) in D425 and UW228 cells. Flow cytometric analysis showed that Ad-DsRed-SP-infected cells accumulate in the G2/M phase of cell cycle. Further, immunoblot and immunoprecipitation analyses revealed that SPARC induced G2/M cell cycle arrest was mediated through inhibition of the Cyclin-B-regulated signaling pathway involving p21 and Cdc2 expression. Additionally, expression of SPARC decreased STAT3 phosphorylation at Tyr-705; constitutively active STAT3 expression reversed SPARC induced G2/M arrest. Ad-DsRed-SP significantly inhibited the pre-established orthotopic tumor growth and tumor volume in nude-mice. Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed decreased immunoreactivity for pSTAT3 and increased immunoreactivity for p21 compared to tumor section from mice treated with mock and Ad-DsRed. Taken together our studies further reveal that STAT3 plays a key role in SPARC induced G2/M arrest in medulloblastoma cells. These new findings provide a molecular basis for the mechanistic understanding of the

  15. Protein PSMD8 may mediate microgravity-induced cell cycle arrest

    NASA Astrophysics Data System (ADS)

    Hang, Xiaoming; Sun, Yeqing; Xu, Dan; Wu, Di; Chen, Xiaoning

    Microgravity environment of space can induce a serial of changes in cells, such as morphology alterations, cytoskeleton disorder and cell cycle disturbance. Our previous study of simulated-microgravity on zebrafish (Danio rerio) embryos demonstrated 26s proteasome non-ATPase regulatory subunit 8 (PSMD8) might be a microgravity sensitive gene. However, functional study on PSMD8 is very limited and it has not been cloned in zebrafish till now. In this study, we tried to clone PSMD8 gene in zebrafish, quantify its protein expression level in zebrafish embryos after simulated microgravity and identify its possible function in cell cycle regulation. A rotary cell culture system (RCCS) designed by national aeronautics and apace administration (NASA) of America was used to simulate microgravity. The full-length of psmd8 gene in zebrafish was cloned. Preliminary analysis on its sequence and phylogenetic tree construction were carried out subsequently. Quantitative analysis by western blot showed that PSMD8 protein expression levels were significantly increased 1.18 and 1.22 times after 24-48hpf and 24-72hpf simulated microgravity, respectively. Moreover, a significant delay on zebrafish embryo development was found in simulated-microgravity exposed group. Inhibition of PSMD8 protein in zebrafish embryonic cell lines ZF4 could block cell cycle in G1 phase, which indicated that PSMD8 may play a role in cell cycle regulation. Interestingly, simulated-microgravity could also block ZF4 cell in G1 phase. Whether it is PSMD8 mediated cell cycle regulation result in the zebrafish embryo development delay after simulated microgravity exposure still needs further study. Key Words: PSMD8; Simulated-microgravity; Cell cycle; ZF4 cell line

  16. Fusarochromanone Induces G1 Cell Cycle Arrest and Apoptosis in COS7 and HEK293 Cells

    PubMed Central

    Gu, Ying; Chen, Xin; Shang, Chaowei; Singh, Karnika; Barzegar, Mansoureh; Mahdavian, Elahe; Salvatore, Brian A.; Jiang, Shanxiang; Huang, Shile

    2014-01-01

    Fusarochromanone (FC101), a mycotoxin produced by the fungus Fusarium equiseti, is frequently observed in the contaminated grains and feedstuffs, which is toxic to animals and humans. However, the underlying molecular mechanism remains to be defined. In this study, we found that FC101 inhibited cell proliferation and induced cell death in COS7 and HEK293 cells in a concentration-dependent manner. Flow cytometric analysis showed that FC101 induced G1 cell cycle arrest and apoptosis in the cells. Concurrently, FC101 downregulated protein expression of cyclin D1, cyclin-dependent kinases (CDK4 and CDK6), and Cdc25A, and upregulated expression of the CDK inhibitors (p21Cip1 and p27Kip1), resulting in hypophosphorylation of Rb. FC101 also inhibited protein expression of Bcl-2, Bcl-xL, Mcl-1 and survivin, and induced expression of BAD, leading to activation of caspase 3 and cleavage of PARP, indicating caspase-dependent apoptosis. However, Z-VAD-FMK, a pan-caspase inhibitor, only partially prevented FC101-induced cell death, implying that FC101 may induce cell death through both caspase-dependent and -independent mechanisms. Our results support the notion that FC101 executes its toxicity at least by inhibiting cell proliferation and inducing cell death. PMID:25384025

  17. Ambient ionization and direct identification of volatile organic compounds with microwave-induced plasma mass spectrometry.

    PubMed

    Li, Dandan; Tian, Yong-Hui; Zhao, Zhongjun; Li, Wenwen; Duan, Yixiang

    2015-02-01

    An innovative method of volatile organic compounds analysis by using microwave-induced plasma ionization (MIPI) source in combination with an ambient ion trap mass spectrometer is presented here. Using MIPI for direct sample vapor, analysis was achieved without any sample preparation or subsequent heating. The relative abundance of the target compounds can be obtained almost instantly within a few seconds. The ionization processes of different volatile compounds was optimized, and the limits of detection were identified in the range of 0.15-4.5 pptv or 0.73-8.80 pg ml(-1). The relative standard deviation (RSD) is in the range of 4-14%, while correlation coefficients of the working curves (R(2)) are better than 0.98. The new method possesses advantages of ease operation, time-saving, high sensitivity and inexpensive setup. In addition, the ionization processes of short n-alkane chains were investigated with the MIPI technique, and a unique [M + 13](+) was detected, which has not been reported in detail by any other related ionization techniques. An ionization mechanism was proposed on the basis of the experimental results obtained in this work and available information in literatures, in which the n-alkanes in the plasma environment possibly generate protonated cyclopentadiene [M - 5](+) or alkyl-substituted analogues as well as hydrous ions [M + 13](+) and [M + 13 + 18](+), as shown in Scheme 1 in the main text. PMID:25800021

  18. Effects of ply thickness on thermal cycle induced damage and thermal strain

    NASA Technical Reports Server (NTRS)

    Tompkins, Stephen S.

    1994-01-01

    An experimental study was conducted to determine the effects of ply thickness in composite laminates on thermally induced cracking and changes in the coefficient of thermal expansion, CTE. A graphite-epoxy composite material, P75/ERL 1962, in thin (1 mil) and thick (5 mils) prepregs was used to make cross-ply laminates, ((0/90)(sub n))s, with equal total thickness (n=2, n=10) and cross-ply laminates with the same total number of plies (n=2). Specimens of each laminate configuration were cycled up to 1500 times between -250 and 250 F. Thermally induced microdamage was assessed as a function of the number of cycles as was the change in CTE. The results showed that laminates fabricated with thin-plies microcracked at significantly different rates and reached significantly different equilibrium crack densities than the laminate fabricated with thick-ply and n=2. The CTE of thin-ply laminates was less affected by thermal cycling and damage than the CTE of thick-ply laminates. These differences are attributed primarily to differences in interply constraints. Observed effects of ply thickness on crack density was qualitatively predicted by a combined shear-lag stress/energy method.

  19. Solar Cycle Variability in Mean Thermospheric Composition and Temperature Induced by Atmospheric Tides

    NASA Astrophysics Data System (ADS)

    Jones, M., Jr.; Forbes, J. M.; Hagan, M. E.

    2015-12-01

    Vertically-propagating atmospheric thermal tides whose origins lie in Earth's lower atmosphere are now widely recognized as one of the dominant "meteorological" drivers of space weather. Many prior research efforts have focused on documenting and understanding the role that dissipating tides play in determining the longitudinal and seasonal variability associated with lower thermospheric winds, temperature, and constituent densities. However, considerably less attention has focused on understanding the potential solar cycle variability in the mean thermospheric state induced by the tides. In this paper we utilize the National Center for Atmospheric Research Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIE-GCM), forced with observationally-based tides at the model lower boundary from the Climatological Tidal Model of the Thermosphere (CTMT, from Oberheide et al. [2011]), to elucidate how the dissipating tides induce variations of up to 30 K in the zonal-mean thermosphere temperature between solar minimum and maximum. Numerical experiments are performed for the month of September and for solar minimum, medium, and maximum conditions in order to quantify the solar cycle variability associated with the different terms in the thermodynamic energy, major and minor neutral constituent continuity equations. Our analysis indicates that solar cycle variability in neutral temperatures results from a combination of net eddy heat transport effects and tidal modulation of net nitric oxide (NO) cooling. The chemical and dynamical pathways through which dissipating tides affect mean NO cooling differently at solar minimum and maximum are diagnosed.

  20. Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell cycle arrest

    PubMed Central

    Raz, S; Sheban, D; Gonen, N; Stark, M; Berman, B; Assaraf, Y G

    2014-01-01

    Antifolates have a crucial role in the treatment of various cancers by inhibiting key enzymes in purine and thymidylate biosynthesis. However, the frequent emergence of inherent and acquired antifolate resistance in solid tumors calls for the development of novel therapeutic strategies to overcome this chemoresistance. The core of solid tumors is highly hypoxic due to poor blood circulation, and this hypoxia is considered to be a major contributor to drug resistance. However, the cytotoxic activity of antifolates under hypoxia is poorly characterized. Here we show that under severe hypoxia, gene expression of ubiquitously expressed key enzymes and transporters in folate metabolism and nucleoside homeostasis is downregulated. We further demonstrate that carcinoma cells become completely refractory, even at sub-millimolar concentrations, to all hydrophilic and lipophilic antifolates tested. Moreover, tumor cells retained sensitivity to the proteasome inhibitor bortezomib and the topoisomerase II inhibitor doxorubicin, which are independent of cell cycle. We provide evidence that this antifolate resistance, associated with repression of folate metabolism, is a result of the inability of antifolates to induce DNA damage under hypoxia, and is attributable to a hypoxia-induced cell cycle arrest, rather than a general anti-apoptotic mechanism. Our findings suggest that solid tumors harboring a hypoxic core of cell cycle-arrested cells may display antifolate resistance while retaining sensitivity to the chemotherapeutics bortezomib and doxorubicin. This study bears important implications for the molecular basis underlying antifolate resistance under hypoxia and its rational overcoming in solid tumors. PMID:24556682

  1. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction

    PubMed Central

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2016-01-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction. PMID:26235983

  2. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction.

    PubMed

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2015-10-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction. PMID:26235983

  3. Induced root-secreted phenolic compounds as a belowground plant defense.

    PubMed

    Lanoue, Arnaud; Burlat, Vincent; Schurr, Ulrich; Röse, Ursula S R

    2010-08-01

    Rhizosphere is the complex place of numerous interactions between plant roots, microbes and soil fauna. Whereas plant interactions with aboveground organisms are largely described, unravelling plant belowground interactions remains challenging. Plant root chemical communication can lead to positive interactions with nodulating bacteria, mycorriza or biocontrol agents or to negative interactions with pathogens or root herbivores. A recent study suggested that root exudates contribute to plant pathogen resistance via secretion of antimicrobial compounds. These findings point to the importance of plant root exudates as belowground signalling molecules, particularly in defence responses. In our report, we showed that under Fusarium attack the barley root system launched secretion of phenolic compounds with antimicrobial activity. The secretion of de novo biosynthesized t-cinnamic acid induced within 2 days illustrates the dynamic of plant defense mechanisms at the root level. We discuss the costs and benefits of induced defense responses in the rhizosphere. We suggest that plant defence through root exudation may be cultivar dependent and higher in wild or less domesticated varieties. PMID:20699651

  4. Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells.

    PubMed

    Ma, Li-Li; Wang, Da-Wei; Yu, Xu-Dong; Zhou, Yan-Ling

    2016-07-01

    Tangeretin (TANG), present in peel of citrus fruits, has been shown to various medicinal properties such as chemopreventive and neuroprotective. However, the chemopreventive effect of TANG on glioblastoma cells has not been examined. The present study was designed to explore the anticancer potential of TANG in glioblastoma cells and to investigate the related mechanism. Human glioblastoma U-87MG and LN-18 cells were treated with 45μM concentration of TANG and cell growth was measured by MTT assay. The cell cycle distribution and cell death were measured by flow cytometry. The expression of cell cycle and apoptosis related genes were analyzed by quantitative RT-PCR and western blot. The cells treated with TANG were significantly increased cell growth suppression and cell death effects than vehicle treated cells. Further, TANG treatment increases G2/M arrest and apoptosis by modulating PTEN and cell-cycle regulated genes such as cyclin-D and cdc-2 mRNA and protein expressions. Moreover, the ability of TANG to decrease cell growth and to induce cell death was compromised when PTEN was knockdown by siRNA. Taken together, the chemopreventive effect of TANG is associated with regulation of cell-cycle and apoptosis in glioblastoma, thereby attenuating glioblastoma cell growth. Hence, the present findings suggest that TANG may be a therapeutic agent for glioblastoma treatment. PMID:27261630

  5. Flavonoid-induced conversion of catalase to its inactive form--Compound II.

    PubMed

    Krych, J; Gebicki, J L; Gebicka, L

    2014-11-01

    Flavonoids (FlaOHs), plant polyphenols, are ubiquitous components of human diet and are known as antioxidants. However, their prooxidant activity has also been reported. We have recently found that FlaOHs inhibit catalase, the heme enzyme which catalyzes the decomposition of hydrogen peroxide (H2O2) into water and molecular oxygen. The catalytic cycle proceeds with the formation of the intermediate, Compound I (Cpd I), an oxoferryl porphyrin π-cation radical, the two-electron oxidation product of a heme group. Under conditions of low H2O2 fluxes and in the presence of an appropriate substrate, Cpd I can undergo one-electron reduction to inactive Compound II (Cpd II), oxoferryl derivative without radical site. Here we show that in vitro, under low fluxes of H2O2, FlaOHs reduce Cpd I to inactive Cpd II. Measurable amounts of Cpd II can be formed even in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) at concentration comparable with the investigated FlaOHs. Possible mechanisms of electron transfer from FlaOH molecule to the heme are discussed. PMID:25111015

  6. Onset of penicillin-induced bacteriolysis in staphylococci is cell cycle dependent.

    PubMed Central

    Maidhof, H; Johannsen, L; Labischinski, H; Giesbrecht, P

    1989-01-01

    Synchronously growing staphylococci were treated with "lytic" concentrations of penicillin at different stages of their division cycle. Coulter Counter measurements and light microscopy were used to determine the onset of bacteriolysis. Independent of the stage of the division cycle at which penicillin was added, (i) the cells were always able to perform the next cell division; (ii) the following division, however, did not take place; and (iii) instead, at this time, when the onset of the subsequent cell separation was observed in control cultures, lysis of the penicillin-treated cells occurred. These results support a recent model (P. Giesbrecht, H. Labischinski, and J. Wecke, Arch. Microbiol. 141:315-324, 1985) explaining penicillin-induced bacteriolysis of staphylococci as the result of a special morphogenetic mistake during cross wall formation. Images PMID:2703473

  7. Penicillin Induced Persistence in Chlamydia trachomatis: High Quality Time Lapse Video Analysis of the Developmental Cycle

    PubMed Central

    Barlow, David; Wang, Yibing; Salim, Omar; Lambden, Paul R.; Clarke, Ian N.

    2009-01-01

    Background Chlamydia trachomatis is a major human pathogen with a unique obligate intracellular developmental cycle that takes place inside a modified cytoplasmic structure known as an inclusion. Following entry into a cell, the infectious elementary body (EB) differentiates into a non - infectious replicative form known as a reticulate body (RB). RBs divide by binary fission and at the end of the cycle they redifferentiate into EBs. Treatment of C.trachomatis with penicillin prevents maturation of RBs which survive and enlarge to become aberrant RBs within the inclusion in a non - infective persistent state. Persistently infected individuals may be a reservoir for chlamydial infection. The C.trachomatis genome encodes the enzymes for peptidoglycan (PG) biosynthesis but a PG sacculus has never been detected. This coupled to the action of penicillin is known as the chlamydial anomaly. We have applied video microscopy and quantitative DNA assays to the chlamydial developmental cycle to assess the effects of penicillin treatment and establish a framework for investigating penicillin induced chlamydial persistence. Principal Findings Addition of penicillin at the time of cell infection does not prevent uptake and the establishment of an inclusion. EB to RB transition occurs but bacterial cytokinesis is arrested by the second binary fission. RBs continue to enlarge but not divide in the presence of penicillin. The normal developmental cycle can be recovered by the removal of penicillin although the large, aberrant RBs do not revert to the normal smaller size but remain present to the completion of the developmental cycle. Chromosomal and plasmid DNA replication is unaffected by the addition of penicillin but the arrest of bacterial cytokinesis under these conditions results in RBs accumulating multiple copies of the genome. Conclusions We have applied video time lapse microscopy to the study of the chlamydial developmental cycle. Linked with accurate measures of genome

  8. Niclosamide inhibits the proliferation of human osteosarcoma cell lines by inducing apoptosis and cell cycle arrest.

    PubMed

    Li, Zonghuan; Yu, Yifeng; Sun, Shaoxing; Qi, Baiwen; Wang, Weiyang; Yu, Aixi

    2015-04-01

    Niclosamide, used as an antihelminthic, has demonstrated some properties of anticancer effects. However, its role in osteosarcoma remains to be determined. The aim of this study was to determine the effect of niclosamide on human osteosarcoma cell lines. The human MG-63 and U2OS osteosarcoma cell lines were treated with different concentrations of niclosamide. The cell inhibitory rate was calculated by CCK-8 assay. Cell cycle was detected by flow cytometry. Cell apoptosis was determined by Hoechst 33324 staining, flow cytometry and fluorescence microscope, respectively. The expression of bcl-2, bax and pro-caspase-3 were measured by western blotting. Niclosamide exerted an inhibitory effect on the two cell lines in a time- and dose-dependent manner. Niclosamide was found to induce the arrest of S and G2/M phase in U2OS cells and G2/M in MG-63 cells. Moreover, niclosamide induced apoptosis in MG-63 and U2OS cells. The bax/bcl-2 ratio increased while the expression of pro‑caspase-3 decreased significantly in the two cell lines. The results indicated that niclosamide inhibits proliferation, and induces apoptosis and cell cycle arrest in human osteosarcoma cell lines. PMID:25634333

  9. Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response

    PubMed Central

    Bujdoso, Raymond; Landgraf, Matthias; Jackson, Walker S; Thackray, Alana M

    2015-01-01

    Protein misfolding neurodegenerative diseases arise through neurotoxicity induced by aggregation of host proteins. These conditions include Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, motor neuron disease, tauopathies and prion diseases. Collectively, these conditions are a challenge to society because of the increasing aged population and through the real threat to human food security by animal prion diseases. It is therefore important to understand the cellular and molecular mechanisms that underlie protein misfolding-induced neurotoxicity as this will form the basis for designing strategies to alleviate their burden. Prion diseases are an important paradigm for neurodegenerative conditions in general since several of these maladies have now been shown to display prion-like phenomena. Increasingly, cell cycle activity and the DNA damage response are recognised as cellular events that participate in the neurotoxic process of various neurodegenerative diseases, and their associated animal models, which suggests they are truly involved in the pathogenic process and are not merely epiphenomena. Here we review the role of cell cycle activity and the DNA damage response in neurodegeneration associated with protein misfolding diseases, and suggest that these events contribute towards prion-induced neurotoxicity. In doing so, we highlight PrP transgenic Drosophila as a tractable model for the genetic analysis of transmissible mammalian prion disease. PMID:26279981

  10. High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.

    PubMed

    Shim, Hee Jin; Lee, Eun-Mi; Nguyen, Long Duy; Shim, Jaekyung; Song, Young-Han

    2014-01-01

    Ionizing radiation (IR) treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs) generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis. PMID:24551207

  11. Glutathione cycle activity and pyridine nucleotide levels in oxidant-induced injury of cells.

    PubMed Central

    Schraufstätter, I U; Hinshaw, D B; Hyslop, P A; Spragg, R G; Cochrane, C G

    1985-01-01

    Exposure of target cells to a bolus of H2O2 induced cell lysis after a latent period of several hours, which was prevented only when the H2O2 was removed within the first 30 min of injury by addition of catalase. This indicated that early metabolic events take place that are important in the fate of the cell exposed to oxidants. In this study, we described two early and independent events of H2O2-induced injury in P388D1 macrophagelike tumor cells: activation of the glutathione cycle and depletion of cellular NAD. Glutathione cycle and hexose monophosphate shunt (HMPS) were activated within seconds after the addition of H2O2. High HMPS activity maintained glutathione that was largely reduced. However, when HMPS activity was inhibited--by glucose depletion or by incubation at 4 degrees C--glutathione remained in the oxidized state. Total pyridine nucleotide levels were diminished when cells were exposed to H2O2, and the breakdown product, nicotinamide, was recovered in the extracellular medium. Intracellular NAD levels fell by 80% within 20 min of exposure of cells to H2O2. The loss of NADP(H) and stimulation of the HMPS could be prevented when the glutathione cycle was inhibited by either blocking glutathione synthesis with buthionine sulfoximine (BSO) or by inhibiting glutathione reductase with (1,3-bis) 2 chlorethyl-1-nitrosourea. The loss of NAD developed independently of glutathione cycle and HMPS activity, as it also occurred in BSO-treated cells. PMID:3840176

  12. Toxic but Drank: Gustatory Aversive Compounds Induce Post-ingestional Malaise in Harnessed Honeybees

    PubMed Central

    Ayestaran, Ainara

    2010-01-01

    Background Deterrent substances produced by plants are relevant due to their potential toxicity. The fact that most of these substances have an unpalatable taste for humans and other mammals contrasts with the fact that honeybees do not reject them in the range of concentrations in which these compounds are present in flower nectars. Here we asked whether honeybees detect and ingest deterrent substances and whether these substances are really toxic to them. Results We show that pairing aversive substances with an odor retards learning of this odor when it is subsequently paired with sucrose. Harnessed honeybees in the laboratory ingest without reluctance a considerable volume (20 µl) of various aversive substances, even if some of them induce significant post-ingestional mortality. These substances do not seem, therefore, to be unpalatable to harnessed bees but induce a malaise-like state that in some cases results in death. Consistently with this finding, bees learning that one odor is associated with sugar, and experiencing in a subsequent phase that the sugar was paired with 20 µl of an aversive substance (devaluation phase), respond less than control bees to the odor and the sugar. Such stimulus devaluation can be accounted for by the malaise-like state induced by the aversive substances. Conclusion Our results indicate that substances that taste bitter to humans as well as concentrated saline solutions base their aversive effect on the physiological consequences that their ingestion generates in harnessed bees rather than on an unpalatable taste. This conclusion is only valid for harnessed bees in the laboratory as freely-moving bees might react differently to aversive compounds could actively reject aversive substances. Our results open a new possibility to study conditioned taste aversion based on post-ingestional malaise and thus broaden the spectrum of aversive learning protocols available in honeybees. PMID:21060877

  13. The adverse effects of high fat induced obesity on female reproductive cycle and hormones

    NASA Astrophysics Data System (ADS)

    Donthireddy, Laxminarasimha Reddy

    The prevalence of obesity, an established risk and progression factor for abnormal reproductive cycle and tissue damage in female mice. It leads to earlier puberty, menarche in young females and infertility. There are extensive range of consequences of obesity which includes type-2 diabetes, cardiovascular disease and insulin resistance. Obesity is the interaction between dietary intake, genes, life style and environment. The interplay of hormones estrogen, insulin, and leptin is well known on energy homeostasis and reproduction. The aim of this study is to determine the effect of high fat induced obesity on reproductive cycles and its hormonal abnormalities on mice model. Two week, 3 month and 8 month long normal (WT) and very high fat diet (VHFD) diet course is followed. When mice are fed with very high fat diet, there is a drastic increase in weight within the first week later. There was a significant (p<0.001) increase in leptin levels in 6 month VHFD treated animals. 2 week, 3 month and 6 month time interval pap smear test results showed number of cells, length of estrous cycle and phases of the estrous cycle changes with VHFD mice(n=30) compared to normal diet mice(n=10). These results also indicate that the changes in the reproductive cycles in VHFD treated female mice could be due to the changes in hormones. Histo-pathological analyses of kidney, ovary, liver, pancreas, heart and lungs showed remarkable changes in some tissue on exposure to very high fat. Highly deposited fat packets observed surrounding the hepatocytes and nerve cells.

  14. Thermal cycling induced load on copper-ribbons in crystalline photovoltaic modules

    NASA Astrophysics Data System (ADS)

    Meier, R.; Kraemer, F.; Wiese, S.; Wolter, K.-J.; Bagdahn, J.

    2010-08-01

    Solar module lifetime is limited by the fatigue behavior of its cell interconnectors: the copper-ribbons. Every change in temperature induces thermo-mechanical stresses in the module components due to their thermo-mechanical mismatch. The purpose of this work is to quantify this load on the copper-ribbons between the individual cells of a cell string during a thermal cycling test by measuring cell displacement using digital image correlation and to compare the results to finite element analysis (FEM). Furthermore with help of FEM the influences of different materials were investigated, allowing material and layout optimizations with respect to copper-ribbon loading.

  15. The Resveratrol Tetramer r-Viniferin Induces a Cell Cycle Arrest Followed by Apoptosis in the Prostate Cancer Cell Line LNCaP.

    PubMed

    Empl, Michael T; Albers, Malena; Wang, Shan; Steinberg, Pablo

    2015-10-01

    Polyphenols are secondary plant metabolites that possess potentially health-promoting properties and which occur in various edible plants and plant products. Especially the stilbenoid resveratrol has been extensively studied regarding its anticarcinogenic and chemopreventive activities. However, research has recently focused on the investigation of other natural or synthetic compounds in order to find substances that show a higher bioactivity and/or bioavailability than resveratrol. In this context, we exemplarily investigated the cytotoxic/growth-inhibiting properties of the resveratrol tetramer r-viniferin on the prostate cancer cell line LNCaP and compared them with those of resveratrol. By using the sulforhodamine B assay followed by cell cycle analysis via flow cytometry and commercially available apoptosis/necrosis assay kits, we show that both compounds were able to inhibit the growth of LNCaP cells and to induce a cell cycle arrest in the G1 phase. However, r-viniferin was significantly more potent in inhibiting cellular growth than resveratrol and the only compound that increased the apoptotic cellular fraction as well as the activity of apoptosis-associated enzymes. In conclusion, r-viniferin leads to cytotoxicity in LNCaP cells at fairly low concentrations, and it is therefore conceivable that it might be used as a chemopreventive agent or as an adjuvant in prostate cancer therapy. PMID:26331691

  16. SMG1 and NIK regulate apoptosis induced by Smac mimetic compounds

    PubMed Central

    Cheung, H H; St Jean, M; Beug, S T; Lejmi-Mrad, R; LaCasse, E; Baird, S D; Stojdl, D F; Screaton, R A; Korneluk, R G

    2011-01-01

    Smac mimetic compounds (SMCs) are experimental small molecules that induce tumour necrosis factor alpha (TNFα)-dependent cancer cell death by targeting the inhibitor of apoptosis proteins. However, many cancer cell lines are resistant to SMC-mediated apoptosis despite the presence of TNFα. To add insight into the mechanism of SMC-resistance, we used functional siRNA-based kinomic and focused chemical screens and identified suppressor of morphogenesis in genitalia-1 (SMG1) and NF-κB-inducing kinase (NIK) as novel protective factors. Both SMG1 and NIK prevent SMC-mediated apoptosis likely by maintaining FLICE inhibitory protein (c-FLIP) levels to suppress caspase-8 activation. In SMC-resistant cells, the accumulation of NIK upon SMC treatment enhanced the activity of both the classical and alternative nuclear factor-κB pathways, and increased c-FLIP mRNA levels. In parallel, persistent SMG1 expression in SMC-resistant cells repressed SMC-mediated TNFα-induced JNK activation and c-FLIP levels were sustained. Importantly, SMC-resistance is overcome by depleting NIK and SMG1, which appear to facilitate the downregulation of c-FLIP in response to SMC and TNFα treatment, leading to caspase-8-dependent apoptosis. Collectively, these data show that SMG1 and NIK function as critical repressors of SMC-mediated apoptosis by potentially converging on the regulation of c-FLIP metabolism. PMID:21490678

  17. Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer cells

    PubMed Central

    Tang, Yuzhe; Chen, Ruibao; Huang, Yan; Li, Guodong; Huang, Yiling; Chen, Jiepeng; Duan, Lili; Zhu, Bao-Ting; Thrasher, J Brantley; Zhang, Xu; Li, Benyi

    2014-01-01

    Prostate cancers at the late stage of castration resistance are not responding well to most of current therapies available in clinic, reflecting a desperate need of novel treatment for this life-threatening disease. In this study, we evaluated the anti-cancer effect of a recently isolated natural compound Alternol in multiple prostate cancer cell lines with the properties of advanced prostate cancers in comparison to prostate-derived non-malignant cells. As assessed by trypan blue exclusion assay, a significant cell death was observed in all prostate cancer cell lines except DU145 but not in non-malignant (RWPE-1and BPH1) cells. Further analyses revealed that Alternol-induced cell death was an apoptotic response in a dose- and time-dependent manner, as evidenced by the appearance of apoptosis hallmarks such as Caspase-3 processing and PARP cleavage. Interestingly, Alternol-induced cell death was completely abolished by reactive oxygen species (ROS) scavengers, N-acetylcysteine (N-Ac) and dihydrolipoic acid (DHLA). We also demonstrated that the pro-apoptotic Bax protein was activated after Alternol treatment and was critical for Alternol-induced apoptosis. Animal xenograft experiments in nude mice showed that Alternol treatment largely suppressed tumor growth of PC-3 xenografts but not Bax-null DU-145 xenografts in vivo. These data suggest that Alternol might serve as a novel anticancer agent for late stage prostate cancer patient. PMID:24688053

  18. YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways

    PubMed Central

    Xue, Bingjie; Huang, Wei; Yuan, Xia; Xu, Bo; Lou, Yaxin; Zhou, Quan; Ran, Fuxiang; Ge, Zemei; Li, Runtao; Cui, Jingrong

    2015-01-01

    Given that the proteasome is essential for multiple cellular processes by degrading diverse regulatory proteins, inhibition of the proteasome has emerged as an attractive target for anti-cancer therapy. YSY01A is a novel small molecule compound targeting the proteasome. The compound was found to suppress viability of MCF-7 cells and cause limited cell membrane damage as determined by sulforhodamine B assay (SRB) and CytoTox 96® non-radioactive cytotoxicity assay. High-content screening (HCS) further shows that YSY01A treatment induces cell cycle arrest on G2 phase within 24 hrs. Label-free quantitative proteomics (LFQP), which allows extensive comparison of cellular responses following YSY01A treatment, suggests that various regulatory proteins including cell cycle associated proteins and PI3K/Akt pathway may be affected. Furthermore, YSY01A increases p-CDC-2, p-FOXO3a, p53, p21Cip1 and p27Kip1 but decreases p-Akt, p-ERα as confirmed by Western blotting. Therefore, YSY01A represents a potential therapeutic for breast cancer MCF-7 by inducing G2 phase arrest via ERα and PI3K/Akt pathways. PMID:25767601

  19. Biphenyl compounds are hydroxyl radical scavengers: their effective inhibition for UV-induced mutation in Salmonella typhimurium TA102.

    PubMed

    Fujita, S; Taira, J

    1994-09-01

    In our previous study, we found several hydroxylated biphenyl compounds have a great scavenging effect for hydroxyl radicals (.OH). In this study, to elucidate the relationship between generation of the .OH and photo-mutagenesis, six biphenyl compounds such as dehydrodieugenol, dehydrodivanillyl alcohol, dehydrodidihydroeugenol, dehydrodicreosol, magnolol and honokiol, respectively, were examined for their ability to inhibit UV-induced mutation in Salmonella typhimurium TA102. The relative mutagenic activities (RMA, %) indicated the mutation frequency of treated cells divided by the mutation frequency of control cells times 100%. The RMA (%) are as follows: 28 +/- 1, 31 +/- 1, 33 +/- 1, 41 +/- 2, 62 +/- 1, and 62 +/- 4 at concentrations of 5 micrograms per plate for dehydrodieugenol, dehydrodivanillyl alcohol, dehydrodidihydroeugenol, dehydrodicreosol, magnolol, and honokiol, respectively. These values indicate that low concentrations of these biphenyl compounds effectively suppress UV-induced mutagenesis. Also, these compounds acted as effective antimutagens in a dose-dependent manner (0.00005-5 micrograms per plate). These compounds are effective .OH scavengers. Consequently, the results obtained above suggest that these compounds could inhibit against UV-induced mutations by scavenging of .OH generated by UV irradiation. The results also suggest that .OH are associated with UV-induced mutation in Salmonella typhimurium TA102. PMID:7982632

  20. Phyllostachys edulis Compounds Inhibit Palmitic Acid-Induced Monocyte Chemoattractant Protein 1 (MCP-1) Production

    PubMed Central

    Higa, Jason K.; Liang, Zhibin; Williams, Philip G.; Panee, Jun

    2012-01-01

    Background Phyllostachys edulis Carriere (Poaceae) is a bamboo species that is part of the traditional Chinese medicine pharmacopoeia. Compounds and extracts from this species have shown potential applications towards several diseases. One of many complications found in obesity and diabetes is the link between elevated circulatory free fatty acids (FFAs) and chronic inflammation. This study aims to present a possible application of P. edulis extract in relieving inflammation caused by FFAs. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is a pro-inflammatory cytokine implicated in chronic inflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) are transcription factors activated in response to inflammatory stimuli, and upregulate pro-inflammatory cytokines such as MCP-1. This study examines the effect of P. edulis extract on cellular production of MCP-1 and on the NF-κB and AP-1 pathways in response to treatment with palmitic acid (PA), a FFA. Methodology/Principal Findings MCP-1 protein was measured by cytometric bead assay. NF-κB and AP-1 nuclear localization was detected by colorimetric DNA-binding ELISA. Relative MCP-1 mRNA was measured by real-time quantitative PCR. Murine cells were treated with PA to induce inflammation. PA increased expression of MCP-1 mRNA and protein, and increased nuclear localization of NF-κB and AP-1. Adding bamboo extract (BEX) inhibited the effects of PA, reduced MCP-1 production, and inhibited nuclear translocation of NF-κB and AP-1 subunits. Compounds isolated from BEX inhibited MCP-1 secretion with different potencies. Conclusions/Significance PA induced MCP-1 production in murine adipose, muscle, and liver cells. BEX ameliorated PA-induced production of MCP-1 by inhibiting nuclear translocation of NF-κB and AP-1. Two O-methylated flavones were isolated from BEX with functional effects on MCP-1 production. These results may represent a possible therapeutic

  1. Vapor Compression Cycle Design Program (CYCLE_D)

    National Institute of Standards and Technology Data Gateway

    SRD 49 NIST Vapor Compression Cycle Design Program (CYCLE_D) (PC database for purchase)   The CYCLE_D database package simulates the vapor compression refrigeration cycles. It is fully compatible with REFPROP 9.0 and covers the 62 single-compound refrigerants . Fluids can be used in mixtures comprising up to five components.

  2. 6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms.

    PubMed

    Wu, Jung-Ju; Omar, Hany A; Lee, Ying-Ray; Teng, Yen-Ni; Chen, Pin-Shern; Chen, Yu-Chung; Huang, Hsiao-Shan; Lee, Kuan-Han; Hung, Jui-Hsiang

    2015-09-01

    Shogaols are a group of the active constituents of ginger that have been identified to have various biological activities. The aim of the current study was to investigate the antitumor activity of 6-shogaol in hepatocellular carcinoma (HCC) and the possible involvement of reactive oxygen species as a putative mechanism of action. HCC cell lines, HepG2 and Huh-7, were used to study the in vitro anti-cancer activity of 6-shogaol via the application of various molecular biology techniques. Results showed that 6-shogaol effectively inhibited the cell viability, caused cell cycle arrest at G2/M phase and induced apoptosis in HCC cells as indicated by MTT assay, DAPI nuclear staining, annexin V assay, cell cycle analysis, and activation of caspase-3. Western blot analysis revealed the ability of 6-shogaol to target cancer survival signaling pathways mediated by mitogen-activated protein kinase (MAPK), 5' AMP-activated protein kinase (AMPK) and Akt. In addition, 6-Shogaol induced alteration of cyclin proteins expression and caused cleavage of protein kinase C delta. Furthermore, 6-Shogaol was able to induce the production of reactive oxygen species and endoplasmic reticulum (ER) stress-associated proteins and the consequent activation of autophagy in HepG2 cells. Taken together, the current study highlights evidences that 6-shogaol induces apoptosis, modulates cyclins expression and targets cancer survival signaling pathways in HCC cell lines, at least in part, via the production of reactive oxygen species. These findings support 6-shogaol's clinical promise as a potential candidate for HCC therapy. PMID:26101062

  3. Xanthatin induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma MKN-45 cells.

    PubMed

    Zhang, Lei; Tao, Li; Ruan, Junshan; Li, Weidong; Wu, Yu; Yan, Linggeng; Zhang, Feng; Fan, Fangtian; Zheng, Shizhong; Wang, Aiyun; Lu, Yin

    2012-06-01

    Xanthatin, a natural bioactive compound of sesquiterpene lactones, was isolated and purified from air-dried aerial part of Xanthium sibiricum Patrin ex Widder. In the present study, we demonstrated the significant antiproliferative and proapoptotic effects of xanthatin on human gastric carcinoma MKN-45 cells. MTS assay showed that xanthatin produced obvious cytotoxicity in MKN-45 cells with IC50 values of 18.6, 9.3, and 3.9 µM for 12, 24, and 48 h, respectively. Results of flow cytometry analysis indicated that the antiproliferative activity induced by xanthatin might be executed via G2/M cell cycle arrest and proapoptosis in MKN-45 cells. Western blot analysis elucidated that: a) xanthatin downregulated expression of Chk1 and Chk2 and phosphorylation of CDC2, which are known as key G2/M transition regulators; b) xanthatin increased p53 activation, decreased the bcl-2/bax ratio and the levels of downstream procaspase-9 and procaspase-3, which are key regulators in the intrinsic apoptosis pathway; c) xanthatin blocked phosphorylation of NF-κB (p65 subunit) and of IκBα, which might contribute to its proapoptotic effects on MKN-45 cells. In conclusion, our results suggest that xanthatin may have therapeutic potential against human gastric carcinoma. PMID:22532019

  4. Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest.

    PubMed

    Granier, Celine J; Wang, Wei; Tsang, Tiffany; Steward, Ruth; Sabaawy, Hatem E; Bhaumik, Mantu; Rabson, Arnold B

    2014-01-01

    PDCD2 (programmed cell death domain 2) is a highly conserved, zinc finger MYND domain-containing protein essential for normal development in the fly, zebrafish and mouse. The molecular functions and cellular activities of PDCD2 remain unclear. In order to better understand the functions of PDCD2 in mammalian development, we have examined PDCD2 activity in mouse blastocyst embryos, as well as in mouse embryonic stem cells (ESCs) and embryonic fibroblasts (MEFs). We have studied mice bearing a targeted PDCD2 locus functioning as a null allele through a splicing gene trap, or as a conditional knockout, by deletion of exon2 containing the MYND domain. Tamoxifen-induced knockout of PDCD2 in MEFs, as well as in ESCs, leads to defects in progression from the G1 to the S phase of cell cycle, associated with increased levels of p53 protein and p53 target genes. G1 prolongation in ESCs was not associated with induction of differentiation. Loss of entry into S phase of the cell cycle and marked induction of nuclear p53 were also observed in PDCD2 knockout blastocysts. These results demonstrate a unique role for PDCD2 in regulating the cell cycle and p53 activation during early embryonic development of the mouse. PMID:25150276

  5. PDMP sensitizes neuroblastoma to paclitaxel by inducing aberrant cell cycle progression leading to hyperploidy.

    PubMed

    Dijkhuis, Anne-Jan; Klappe, Karin; Jacobs, Susan; Kroesen, Bart-Jan; Kamps, Willem; Sietsma, Hannie; Kok, Jan Willem

    2006-03-01

    The sphingolipid ceramide has been recognized as an important mediator in the apoptotic machinery, and its efficient conversion to glucosylceramide has been associated with multidrug resistance. Therefore, inhibitors of glucosylceramide synthase are explored as tools for treatment of cancer. In this study, we used D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol to sensitize Neuro-2a murine neuroblastoma cells to the microtubule-stabilizing agent paclitaxel. This treatment resulted in a synergistic inhibition of viable cell number increase, which was based on a novel mechanism: (a) After a transient mitotic arrest, cells proceeded through an aberrant cell cycle resulting in hyperploidy. Apoptosis also occurred but to a very limited extent. (b) Hyperploidy was not abrogated by blocking de novo sphingolipid biosynthesis using ISP-1, ruling out involvement of ceramide as a mediator. (c) Cyclin-dependent kinase 1 and 2 activities were synergistically decreased on treatment. In conclusion, instead of inducing apoptosis through ceramide accumulation, D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol by itself affects cell cycle-related proteins in paclitaxel-arrested Neuro-2a cells resulting in aberrant cell cycle progression leading to hyperploidy. PMID:16546973

  6. Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest

    PubMed Central

    Granier, Celine J.; Wang, Wei; Tsang, Tiffany; Steward, Ruth; Sabaawy, Hatem E.; Bhaumik, Mantu; Rabson, Arnold B.

    2014-01-01

    ABSTRACT PDCD2 (programmed cell death domain 2) is a highly conserved, zinc finger MYND domain-containing protein essential for normal development in the fly, zebrafish and mouse. The molecular functions and cellular activities of PDCD2 remain unclear. In order to better understand the functions of PDCD2 in mammalian development, we have examined PDCD2 activity in mouse blastocyst embryos, as well as in mouse embryonic stem cells (ESCs) and embryonic fibroblasts (MEFs). We have studied mice bearing a targeted PDCD2 locus functioning as a null allele through a splicing gene trap, or as a conditional knockout, by deletion of exon2 containing the MYND domain. Tamoxifen-induced knockout of PDCD2 in MEFs, as well as in ESCs, leads to defects in progression from the G1 to the S phase of cell cycle, associated with increased levels of p53 protein and p53 target genes. G1 prolongation in ESCs was not associated with induction of differentiation. Loss of entry into S phase of the cell cycle and marked induction of nuclear p53 were also observed in PDCD2 knockout blastocysts. These results demonstrate a unique role for PDCD2 in regulating the cell cycle and p53 activation during early embryonic development of the mouse. PMID:25150276

  7. Oridonin inhibits tumor growth in glioma by inducing cell cycle arrest and apoptosis.

    PubMed

    Zhang, X-H; Liu, Y-X; Jia, M; Han, J-S; Zhao, M; Ji, S-P; Li, A-M

    2014-01-01

    Glioma is the most common malignant intracranial tumors. Despite newly developed therapies, these treatments mainly target oncogenic signals, and unfortunately, fail to provide enough survival benefit in both human patients and mouse xenograft models, especially the first-generation therapies. Oridonin is purified from the Chinese herb Rabdosia rubescens and considered to exert extensive anti-cancer effects on human tumorigenesis. In this study, we systemically investigated the role of Oridonin in tumor growth and the underlying mechanisms in human glioma. We found that Oridonin inhibited cell proliferations in a dose- and time-dependent manner in both glioma U87 and U251 cells. Moreover, these anti-cancer effects were also confirmed in a mouse model bearing glioma. Furthermore, cell cycle arrest in S phase was observed in Oridonin-mediated growth inhibition by flow cytometry. Cell cycle arrest in S phase led to eventual cell apoptosis, as revealed by Hoechst 33342 staining and annexin V/PI double-staining. The cell apoptosis might be accomplished through a mitochondrial manner. In all, we were the first to our knowledge to report that Oridonin could exert anti-cancer effects on tumor growth in human glioma by inducing cell cycle arrest and eventual cell apoptosis. The identification of Oridonin as a critical mediator of glioma growth may potentiate Oridonin as a novel therapeutic strategies in glioma treatments. PMID:25553351

  8. SOX10 ablation arrests the cell cycle, induces senescence and suppresses melanomagenesis

    PubMed Central

    Cronin, Julia C.; Watkins-Chow, Dawn E.; Incao, Art; Hasskamp, Joanne H.; Schönewolf, Nicola; Aoude, Lauren G.; Hayward, Nicholas K.; Bastian, Boris C.; Dummer, Reinhard; Loftus, Stacie K.; Pavan, William J.

    2013-01-01

    The transcription factor SOX10 is essential for survival and proper differentiation of neural crest cell lineages, where it plays an important role in the generation and maintenance of melanocytes. SOX10 is also highly expressed in melanoma tumors, but a role in disease progression has not been established. Here we report that melanoma tumor cell lines require wild-type SOX10 expression for proliferation, and SOX10 haploinsufficiency reduces melanoma initiation in the metabotropic glutamate receptor 1 (Grm1Tg) transgenic mouse model. Stable SOX10 knockdown in human melanoma cells arrested cell growth, altered cellular morphology, and induced senescence. Melanoma cells with stable loss of SOX10 were arrested in the G1 phase of the cell cycle, with reduced expression in the melanocyte determining factor MITF, elevated expression of p21WAF1 and p27KIP2, hypophosphorylated RB and reduced levels of its binding partner E2F1. Since cell cycle dysregulation is a core event in neoplastic transformation, the role for SOX10 in maintaining cell cycle control in melanocytes suggests a rational new direction for targeted treatment or prevention of melanoma. PMID:23913827

  9. Methamphetamine Alters the Normal Progression by Inducing Cell Cycle Arrest in Astrocytes

    PubMed Central

    Jackson, Austin R.; Shah, Ankit; Kumar, Anil

    2014-01-01

    Methamphetamine (MA) is a potent psychostimulant with a high addictive capacity, which induces many deleterious effects on the brain. Chronic MA abuse leads to cognitive dysfunction and motor impairment. MA affects many cells in the brain, but the effects on astrocytes of repeated MA exposure is not well understood. In this report, we used Gene chip array to analyze the changes in the gene expression profile of primary human astrocytes treated with MA for 3 days. Range of genes were found to be differentially regulated, with a large number of genes significantly downregulated, including NEK2, TTK, TOP2A, and CCNE2. Gene ontology and pathway analysis showed a highly significant clustering of genes involved in cell cycle progression and DNA replication. Further pathway analysis showed that the genes downregulated by multiple MA treatment were critical for G2/M phase progression and G1/S transition. Cell cycle analysis of SVG astrocytes showed a significant reduction in the percentage of cell in the G2/M phase with a concomitant increase in G1 percentage. This was consistent with the gene array and validation data, which showed that repeated MA treatment downregulated the genes associated with cell cycle regulation. This is a novel finding, which explains the effect of MA treatment on astrocytes and has clear implication in neuroinflammation among the drug abusers. PMID:25290377

  10. Early myocardial lesions induced by cardiotoxic compounds in Sprague-Dawley rats.

    PubMed

    Kemi, M; Matsumoto, H; Nomura, Y; Takahashi, R

    1996-07-01

    Early focal myocardial lesions in rats induced by five cardiotoxic compounds were histopathologically observed 1 hr and 4 hr after a single intravenous injection with 1/10 LD50 and LD50. The lesions were observed 1 hr and 4 hr after the treatment with LD50 of isoproterenol (ISP), 4 hr with 1/10 LD50 of ISP, 4 hr with LD50 of hydralazine (HYD), caffeine (CAF) and cyclophosphamide (CYC), but not with adriamycin (ADR). The lesions consisted of homogeneously intensely eosinophilic staining, contraction band formation and fragmentation of cardiac muscle fibers. The lesions were interspersed in the inner one third of the left ventricular walls including the papillary muscles with ISP, HYD and CAF, and were all over the ventricular myocardium with CYC. PMID:8844612

  11. Laser-induced breakdown spectroscopy of whole blood and other liquid organic compounds

    NASA Astrophysics Data System (ADS)

    Melikechi, N.; Ding, H.; Rock, S.; Marcano O., A.; Connolly, D.

    2008-02-01

    We report on laser-induced breakdown spectroscopy (LIBS) of whole blood and other organic fluids. LIBS spectra, in the region 200-970 nm, are measured by recording the radiation emitted by the samples following their ablation in a helium environment. We show that these spectra, although very complex, reveal the presence of elements such as nitrogen, hydrogen, oxygen and carbon and that of important metallic elements such as iron, magnesium, calcium, potassium, and sodium. We compare the measured LIBS spectra of whole blood to that of pure carbon and pure iron and find that in the 200-300 nm region. Nearly 90% of the peaks can be assigned to only these two elements. We also report on similar studies of methanol, ethanol, isopropanol and water solutions of protein molecules of interest to cancer research. We show that using simple numerical algorithms, it is possible to distinguish between complex organic compounds that have nearly the same chemical composition.

  12. Two new compounds from Semen celosiae and their protective effects against CCl₄-induced hepatotoxicity.

    PubMed

    Xue, Qian; Sun, Zhen-Liang; Guo, Mei-Li; Wang, Ying; Zhang, Ge; Wang, Xiao-Kang

    2011-04-01

    Two new oleanolic acid saponins, namely celosin A (1) and celosin B (2), together with six known compounds, stigmasterol, β-sitosterol, β-daucosterol, hexacosoic acid, palmitic acid and stearic acid, were isolated from the ethanolic extract of Semen celosiae. The structures of celosin A (1) and celosin B (2) were determined by spectral analysis (including 1D- and 2D-NMR). The hepatoprotective activity of 1 and 2 with oral doses 1.0, 2.0 and 4.0 mg kg⁻¹ were investigated by carbon tetrachloride CCl₄-induced hepatotoxicity in mice. The results indicate that they have significant hepatoprotective effects, and that these hepatoprotective effects may be due to the antioxidant capability. PMID:20306359

  13. Surface induces different crystal structures in a room temperature switchable spin crossover compound.

    PubMed

    Gentili, Denis; Liscio, Fabiola; Demitri, Nicola; Schäfer, Bernhard; Borgatti, Francesco; Torelli, Piero; Gobaut, Benoit; Panaccione, Giancarlo; Rossi, Giorgio; Degli Esposti, Alessandra; Gazzano, Massimo; Milita, Silvia; Bergenti, Ilaria; Ruani, Giampiero; Šalitroš, Ivan; Ruben, Mario; Cavallini, Massimiliano

    2016-01-01

    We investigated the influence of surfaces in the formation of different crystal structures of a spin crossover compound, namely [Fe(L)2] (LH: (2-(pyrazol-1-yl)-6-(1H-tetrazol-5-yl)pyridine), which is a neutral compound thermally switchable around room temperature. We observed that the surface induces the formation of two different crystal structures, which exhibit opposite spin transitions, i.e. on heating them up to the transition temperature, one polymorph switches from high spin to low spin and the second polymorph switches irreversibly from low spin to high spin. We attributed this inversion to the presence of water molecules H-bonded to the complex tetrazolyl moieties in the crystals. Thin deposits were investigated by means of polarized optical microscopy, atomic force microscopy, X-ray diffraction, X-ray absorption spectroscopy and micro Raman spectroscopy; moreover the analysis of the Raman spectra and the interpretation of spin inversion were supported by DFT calculations. PMID:26575005

  14. A Generic Guiding Principle for the Prediction of Metal-Induced Reconstructions of Compound Semiconductor Surfaces

    SciTech Connect

    Yang, Shenyuan; Zhang, Lixin; Chen, Hua; Wang, Enge; Zhang, Zhenyu

    2008-01-01

    We have performed extensive and systematical ab initio calculations to substantiate a recently proposed generalized electron counting (GEC) rule that governs the rich patterns of compound semiconductor reconstruction induced by metal adsorption. In this rule, the metal adsorbates serve as an electron bath, either donating or accepting the right number of electrons, with which the binary host system chooses a specific reconstruction under the classical electron counting rule, and meanwhile, the adsorbates stay in their optimal valency. The GEC rule is applied to different GaAs surfaces deposited by various classes of metal adsorbates, leading to a number of possible reconstructions, which can be further confirmed by first-principles calculations and/or experiments. The alkali metal adsorption on the GaAs(110) surface up to the saturate coverage is a perfect example of the GEC rule. The application of the GEC rule to the prototype system of Mn/GaAs(001) not only predicts possible reconstruction patterns over a wide range of coverage, but also provides an underlying link between the reconstruction structures and the local magnetic moments of the metal adsorbates. In Au/GaAs(100), we demonstrate the application of the GEC rule to those systems where metal adsrobates form covalent bonds with the substrate. The GEC rule, as a generic principle, is expected to be applicable to more metal-adsorbed compound semiconductor surfaces. PACS numbers: 68.35.-p, 68.43.Bc, 75.70.-i

  15. Pressure induced structural phase transition in IB transition metal nitrides compounds

    NASA Astrophysics Data System (ADS)

    Soni, Shubhangi; Kaurav, Netram; Jain, A.; Shah, S.; Choudhary, K. K.

    2015-06-01

    Transition metal mononitrides are known as refractory compounds, and they have, relatively, high hardness, brittleness, melting point, and superconducting transition temperature, and they also have interesting optical, electronic, catalytic, and magnetic properties. Evolution of structural properties would be an important step towards realizing the potential technological scenario of this material of class. In the present study, an effective interionic interaction potential (EIOP) is developed to investigate the pressure induced phase transitions in IB transition metal nitrides TMN [TM = Cu, Ag, and Au] compounds. The long range Coulomb, van der Waals (vdW) interaction and the short-range repulsive interaction upto second-neighbor ions within the Hafemeister and Flygare approach with modified ionic charge are properly incorporated in the EIOP. The vdW coefficients are computed following the Slater-Kirkwood variational method, as both the ions are polarizable. The estimated value of the phase transition pressure (Pt) and the magnitude of the discontinuity in volume at the transition pressure are consistent as compared to the reported data.

  16. Pressure induced structural phase transition in IB transition metal nitrides compounds

    SciTech Connect

    Soni, Shubhangi; Kaurav, Netram Jain, A.; Shah, S.; Choudhary, K. K.

    2015-06-24

    Transition metal mononitrides are known as refractory compounds, and they have, relatively, high hardness, brittleness, melting point, and superconducting transition temperature, and they also have interesting optical, electronic, catalytic, and magnetic properties. Evolution of structural properties would be an important step towards realizing the potential technological scenario of this material of class. In the present study, an effective interionic interaction potential (EIOP) is developed to investigate the pressure induced phase transitions in IB transition metal nitrides TMN [TM = Cu, Ag, and Au] compounds. The long range Coulomb, van der Waals (vdW) interaction and the short-range repulsive interaction upto second-neighbor ions within the Hafemeister and Flygare approach with modified ionic charge are properly incorporated in the EIOP. The vdW coefficients are computed following the Slater-Kirkwood variational method, as both the ions are polarizable. The estimated value of the phase transition pressure (Pt) and the magnitude of the discontinuity in volume at the transition pressure are consistent as compared to the reported data.

  17. Procaspase-activating compound 1 induces a caspase-3-dependent cell death in cerebellar granule neurons

    SciTech Connect

    Aziz, Gulzeb; Akselsen, Oyvind W.; Hansen, Trond V.; Paulsen, Ragnhild E.

    2010-09-15

    Procaspase-activating compound 1, PAC-1, has been introduced as a direct activator of procaspase-3 and has been suggested as a therapeutic agent against cancer. Its activation of procaspase-3 is dependent on the chelation of zinc. We have tested PAC-1 and an analogue of PAC-1 as zinc chelators in vitro as well as their ability to activate caspase-3 and induce cell death in chicken cerebellar granule neuron cultures. These neurons are non-dividing, primary cells with normal caspase-3. The results reported herein show that PAC-1 chelates zinc, activates procaspase-3, and leads to caspase-3-dependent cell death in neurons, as the specific caspase-3-inhibitor Ac-DEVD-cmk inhibited both the caspase-3 activity and cell death. Thus, chicken cerebellar granule neurons is a suitable model to study mechanisms of interference with apoptosis of PAC-1 and similar compounds. Furthermore, the present study also raises concern about potential neurotoxicity of PAC-1 if used in cancer therapy.

  18. Adamantyl-tethered-biphenylic compounds induce apoptosis in cancer cells by targeting Bcl homologs.

    PubMed

    Anusha, Sebastian; Mohan, Chakrabhavi Dhananjaya; Ananda, Hanumappa; Baburajeev, C P; Rangappa, Shobith; Mathai, Jessin; Fuchs, Julian E; Li, Feng; Shanmugam, Muthu K; Bender, Andreas; Sethi, Gautam; Basappa; Rangappa, Kanchugarakoppal S

    2016-02-01

    Bcl homologs prominently contribute to apoptotic resistance in cancer cells and serve as molecular targets in treatment of various cancers. Herein, we report the synthesis of biphenyl-adamantane derivatives by a ligand free palladium on carbon based Suzuki reaction using diisopropylamine as a base for the coupling of adamantane based aryl chloride with a variety of aryl boronic acids. Among the biphenyl derivatives synthesized, compound 3'-(adamantan-1-yl)-4'-methoxy-[1,1'-biphenyl]-3-ol (AMB) displayed cytotoxic activity against hepatocellular carcinoma cell lines without significantly affecting the normal cell lines. Further, AMB caused increased accumulation of the HCC cells in subG1 phase, decreased the expression of Bcl-2, Bcl-xL, cyclin D1, caspase-3, survivin and increased the cleavage of PARP in a time-dependent manner. In silico molecular interaction studies between Bcl homologs and AMB showed that the biphenyl scaffold is predicted to form π-π interactions with Phe-101 and Tyr-105 and the adamantyl fragment is predicted to occupy another hydrophobic region in the kink region of the binding groove. In summary, we report on the synthesis and biological characterization of adamantyl-tethered biphenylic compounds that induce apoptosis in tumor cells most likely by targeting Bcl homologs. PMID:26725030

  19. Nickel compounds induce histone ubiquitination by inhibiting histone deubiquitinating enzyme activity

    SciTech Connect

    Ke Qingdong; Ellen, Thomas P.; Costa, Max

    2008-04-15

    Nickel (Ni) compounds are known carcinogens but underlying mechanisms are not clear. Epigenetic changes are likely to play an important role in nickel ion carcinogenesis. Previous studies have shown epigenetic effects of nickel ions, including the loss of histone acetylation and a pronounced increase in dimethylated H3K9 in nickel-exposed cells. In this study, we demonstrated that both water-soluble and insoluble nickel compounds induce histone ubiquitination (uH2A and uH2B) in a variety of cell lines. Investigations of the mechanism by which nickel increases histone ubiquitination in cells reveal that nickel does not affect cellular levels of the substrates of this modification, i.e., ubiquitin, histones, and other non-histone ubiquitinated proteins. In vitro ubiquitination and deubiquitination assays have been developed to further investigate possible effects of nickel on enzymes responsible for histone ubiquitination. Results from the in vitro assays demonstrate that the presence of nickel did not affect the levels of ubiquitinated histones in the ubiquitinating assay. Instead, the addition of nickel significantly prevents loss of uH2A and uH2B in the deubiquitinating assay, suggesting that nickel-induced histone ubiquitination is the result of inhibition of (a) putative deubiquitinating enzyme(s). Additional supporting evidence comes from the comparison of the response to nickel ions with a known deubiquitinating enzyme inhibitor, iodoacetamide (IAA). This study is the first to demonstrate such effects of nickel ions on histone ubiquitination. It also sheds light on the possible mechanisms involved in altering the steady state of this modification. The study provides further evidence that supports the notion that nickel ions alter epigenetic homeostasis in cells, which may lead to altered programs of gene expression and carcinogenesis.

  20. Enzyme entrapped nanoporous scaffolds formed through flow induced gelation in microfluidic filter device for sensitive biosensing of organophosphorus compounds

    SciTech Connect

    Lu, Donglai; Shao, Guocheng; Du, Dan; Wang, Jun; Wang, Limin; Wang, Wanjun; Lin, Yuehe

    2011-02-01

    A novel and versatile processing method was developed for the formation of gel scaffolds with in-situ AChE-AuNPs immobilization for biosensing of organophosphorus compounds. The biosensor designed by our new approach shows high sensitivity, selectivity and reactivation efficiency. This flow induced immobilziation technique opens up new pathways for designing simple, fast, biocompatible, and cost-effective process for enhanced sensor performance and on-site testing of a variety of toxic organophosphorus compounds.

  1. The Involvement of Acetaldehyde in Ethanol-Induced Cell Cycle Impairment

    PubMed Central

    Scheer, Marc A.; Schneider, Katrina J.; Finnigan, Rochelle L.; Maloney, Eamon P.; Wells, Mark A.; Clemens, Dahn L.

    2016-01-01

    Background: Hepatocytes metabolize the vast majority of ingested ethanol. This metabolic activity results in hepatic toxicity and impairs the ability of hepatocytes to replicate. Previous work by our group has shown that ethanol metabolism results in a G2/M cell cycle arrest. The intent of these studies was to discern the roles of acetaldehyde and reactive oxygen, two of the major by-products of ethanol metabolism, in the G2/M cell cycle arrest. Methods: To investigate the role of ethanol metabolites in the cell cycle arrest, VA-13 and VL-17A cells were used. These are recombinant Hep G2 cells that express alcohol dehydrogenase or alcohol dehydrogenase and cytochrome P450 2E1, respectively. Cells were cultured with or without ethanol, lacking or containing the antioxidants N-acetylcysteine (NAC) or trolox, for three days. Cellular accumulation was monitored by the DNA content of the cultures. The accumulation of the cyclin-dependent kinase, Cdc2 in the inactive phosphorylated form (p-Cdc2) and the cyclin-dependent kinase inhibitor p21 were determined by immunoblot analysis. Results: Cultures maintained in the presence of ethanol demonstrated a G2/M cell cycle arrest that was associated with a reduction in DNA content and increased levels of p-Cdc2 and p21, compared with cells cultured in its absence. Inclusion of antioxidants in the ethanol containing media was unable to rescue the cells from the cell cycle arrest or these ethanol metabolism-mediated effects. Additionally, culturing the cells in the presence of acetaldehyde alone resulted in increased levels of p-Cdc2 and p21. Conclusions: Acetaldehyde produced during ethanol oxidation has a major role in the ethanol metabolism-mediated G2/M cell cycle arrest, and the concurrent accumulation of p21 and p-Cdc2. Although reactive oxygen species are thought to have a significant role in ethanol-induced hepatocellular damage, they may have a less important role in the inability of hepatocytes to replace dead or damaged

  2. Toxicity of drinking water disinfection byproducts: cell cycle alterations induced by the monohaloacetonitriles.

    PubMed

    Komaki, Yukako; Mariñas, Benito J; Plewa, Michael J

    2014-10-01

    Haloacetonitriles (HANs) are a chemical class of drinking water disinfection byproducts (DBPs) that form from reactions between disinfectants and nitrogen-containing precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. HANs, previously demonstrated to be genotoxic, were investigated for their effects on the mammalian cell cycle. Treating Chinese hamster ovary (CHO) cells with monoHANs followed by the release from the chemical treatment resulted in the accumulation of abnormally high DNA content in cells over time (hyperploid). The potency for the cell cycle alteration followed the order: iodoacetonitrile (IAN) > bromoacetonitrile (BAN) ≫ chloroacetonitrile (CAN). Exposure to 6 μM IAN, 12 μM BAN and 900 μM CAN after 26 h post-treatment incubation resulted in DNA repair; however, subsequent cell cycle alteration effects were observed. Cell proliferation of HAN-treated cells was suppressed for as long as 43 to 52 h. Enlarged cell size was observed after 52 h post-treatment incubation without the induction of cytotoxicity. The HAN-mediated cell cycle alteration was mitosis- and proliferation-dependent, which suggests that HAN treatment induced mitosis override, and that HAN-treated cells proceeded into S phase and directly into the next cell cycle. Cells with multiples genomes would result in aneuploidy (state of abnormal chromosome number and DNA content) at the next mitosis since extra centrosomes could compromise the assembly of bipolar spindles. There is accumulating evidence of a transient tetraploid state proceeding to aneuploidy in cancer progression. Biological self-defense systems to ensure genomic stability and to eliminate tetraploid cells exist in eukaryotic cells. A key tumor suppressor gene, p53, is oftentimes mutated in various types of human cancer. It is possible that HAN disruption of the normal cell cycle and the generation of aberrant cells with an abnormal number of

  3. Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells

    PubMed Central

    García, Víctor; Lara-Chica, Maribel; Cantarero, Irene; Sterner, Olov; Calzado, Marco A.; Muñoz, Eduardo

    2016-01-01

    Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer. PMID:26683224

  4. GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization-embryo transfer cycles.

    PubMed

    Bloch, Miki; Azem, Foad; Aharonov, Inbar; Ben Avi, Irit; Yagil, Yaron; Schreiber, Shaul; Amit, Ami; Weizman, Abraham

    2011-01-01

    To determine whether the use of a GnRH agonist inducing a hypogonadic state during IVF-ET cycles induces negative mood symptoms, we conducted a prospective randomized study in 108 women comparing two different controlled ovarian stimulation protocols. A significant phase effect was observed for depression and anxiety symptoms during IVF-ET cycles reflecting an increase in symptoms between the hypogonadal phase and the peak in gonadotropin stimulation; however, the hypogonadal phase induced by the GnRH agonist was not associated with a significant increase in any of the studied mood parameters. PMID:20801439

  5. The effect of probiotic microorganisms and bioactive compounds on chemically induced carcinogenesis in rats.

    PubMed

    Bertkova, I; Hijova, E; Chmelarova, A; Mojzisova, G; Petrasova, D; Strojny, L; Bomba, A; Zitnan, R

    2010-01-01

    Diet interventions and natural bioactive supplements have now been extensively studied to reduce risks of colon cancer, which is one of the major public health problem throughout the world. The objective of our investigation was to study the effects of probiotic, prebiotic, nutritional plant extract, and plant oil on selected biochemical and immunological parameters in rats with colon cancer induced by N,N dimethylhydrazine (DMH). Male and female Wistar albino rats were were fed by a high-fat (HF) diet (10% fat in the diet) and were divided into 9 groups: Control group; PRO group - HF diet supplemented with probiotic Lactobacillus plantarum to provide 3 x 109 c.f.u. of strain/1 ml of medium; PRE group - HF diet supplemented with inulin enriched with oligofructose (2% of HF diet); HES group - HF diet supplemented with plant extract of Aesculus hippocastanum L. (1% of HF diet); OIL group - HF diet comprised Linioleum virginale (2% of HF diet); and combination of probiotic microorganisms and bioactive compounds in the groups - PRO-PRE, PRO-HES, PRO-OIL, PRE-OIL. Carcinogenesis was initiated with subcutaneous injection of DMH (20 mg/kg) two times at week interval and dietary treatments were continued for the six weeks. Application of probiotic microorganisms and bioactive compounds in all treated groups significantly decreased the activities of bacterial enzymes (p<0.001), the fecal bile acids concentration (p<0.01; p<0.001) and significantly increased serum TNFalpha level (p<0.001) in comparison to the control rats. The number of coliforms was reduced in PRO, PRO-PRE, PRO-OIL and PRE-OIL groups and significantly higher count of lactobacilli (p<0.05) was observed in PRO-PRE, PRO-OIL and PRE-OIL groups in compare with the controls. In conclusion, the results of this study indicate that probiotic microorganisms and bioactive compounds could exert a preventive effect on colon carcinogenesis induced by DMH. PMID:20568896

  6. Unprecedented inhibition of tubulin polymerization directed by gold nanoparticles inducing cell cycle arrest and apoptosis

    NASA Astrophysics Data System (ADS)

    Choudhury, Diptiman; Xavier, Paulrajpillai Lourdu; Chaudhari, Kamalesh; John, Robin; Dasgupta, Anjan Kumar; Pradeep, Thalappil; Chakrabarti, Gopal

    2013-05-01

    The effect of gold nanoparticles (AuNPs) on the polymerization of tubulin has not been examined till now. We report that interaction of weakly protected AuNPs with microtubules (MTs) could cause inhibition of polymerization and aggregation in the cell free system. We estimate that single citrate capped AuNPs could cause aggregation of ~105 tubulin heterodimers. Investigation of the nature of inhibition of polymerization and aggregation by Raman and Fourier transform-infrared (FTIR) spectroscopies indicated partial conformational changes of tubulin and microtubules, thus revealing that AuNP-induced conformational change is the driving force behind the observed phenomenon. Cell culture experiments were carried out to check whether this can happen inside a cell. Dark field microscopy (DFM) combined with hyperspectral imaging (HSI) along with flow cytometric (FC) and confocal laser scanning microscopic (CLSM) analyses suggested that AuNPs entered the cell, caused aggregation of the MTs of A549 cells, leading to cell cycle arrest at the G0/G1 phase and concomitant apoptosis. Further, Western blot analysis indicated the upregulation of mitochondrial apoptosis proteins such as Bax and p53, down regulation of Bcl-2 and cleavage of poly(ADP-ribose) polymerase (PARP) confirming mitochondrial apoptosis. Western blot run after cold-depolymerization revealed an increase in the aggregated insoluble intracellular tubulin while the control and actin did not aggregate, suggesting microtubule damage induced cell cycle arrest and apoptosis. The observed polymerization inhibition and cytotoxic effects were dependent on the size and concentration of the AuNPs used and also on the incubation time. As microtubules are important cellular structures and target for anti-cancer drugs, this first observation of nanoparticles-induced protein's conformational change-based aggregation of the tubulin-MT system is of high importance, and would be useful in the understanding of cancer therapeutics

  7. Carrageenan Induces Cell Cycle Arrest in Human Intestinal Epithelial Cells in Vitro1–3

    PubMed Central

    Bhattacharyya, Sumit; Borthakur, Alip; Dudeja, Pradeep K.; Tobacman, Joanne K.

    2016-01-01

    Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1–10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1–8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6–8 d of CGN exposure, the percentage of cells reentering G0–G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology. PMID:18287351

  8. Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells.

    PubMed

    Tseng, Shuei-Kuen; Chang, Mei-Chi; Su, Cheng-Yao; Chi, Lin-Yang; Chang, Jenny Zwei-Ching; Tseng, Wan-Yu; Yeung, Sin-Yuet; Hsu, Ming-Lun; Jeng, Jiiang-Huei

    2012-08-01

    Betel quid (BQ) chewing is a common oral habit in South Asia and Taiwan. BQ consumption may increase the risk of oral squamous cell carcinoma (OSCC), oral submucous fibrosis (OSF), and periodontitis as well as systemic diseases (atherosclerosis, hypertension, etc.). However, little is known about the toxic effect of BQ components on endothelial cells that play important roles for angiogenesis, carcinogenesis, tissue fibrosis, and cardiovascular diseases. EAhy 926 (EAHY) endothelial cells were exposed to arecoline, a major BQ alkaloid, for various time periods. Cytotoxicity was estimated by 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. The cell cycle distribution of EAHY cells residing in sub-G0/G1, G0/G1, S-, and G2/M phases was analyzed by propidium iodide staining of cellular DNA content and flow cytometry. Some EAHY cells retracted, became round-shaped in appearance, and even detached from the culture plate after exposure to higher concentrations of arecoline (> 0.4 mM). At concentrations of 0.4 and 0.8 mM, arecoline induced significant cytotoxicity to EAHY cells. At similar concentrations, arecoline induced G2/M cell cycle arrest and increased sub-G0/G1 population, a hallmark of apoptosis. Interestingly, prolonged exposure to arecoline (0.1 mM) for 12 and 21 days significantly suppressed the proliferation of EAHY cells, whereas EAHY cells showed adaptation and survived when exposed to 0.05 mM arecoline. These results suggest that BQ components may contribute to the pathogenesis of OSF and BQ chewing-related cardiovascular diseases via toxicity to oral or systemic endothelial cells, leading to impairment of vascular function. During BQ chewing, endothelial damage may be induced by areca nut components and associate with the pathogenesis of OSF, periodontitis, and cardiovascular diseases. PMID:21847594

  9. Cell Cycle-Dependent Mechanisms Underlie Vincristine-Induced Death of Primary Acute Lymphoblastic Leukemia Cells.

    PubMed

    Kothari, Anisha; Hittelman, Walter N; Chambers, Timothy C

    2016-06-15

    Microtubule-targeting agents (MTA), such as the taxanes and vinca alkaloids, are used to treat a variety of cancers due to their ability to perturb microtubule dynamics. In cell culture, MTAs exert their anticancer effects primarily by causing mitotic arrest and cell death. However, accumulating indirect evidence suggests that MTAs may exert their cytotoxicity in human tumors by interfering with interphase microtubules. In this study, we sought to develop and characterize an experimental system in which to test the hypothesis that MTAs induce cell death during interphase. Primary adult acute lymphoblastic leukemia (ALL) cells treated with vincristine only weakly exhibited colocalization between mitotic and apoptotic markers and major characteristics of mitotic death, such as an increase in cells with 4N DNA content before the appearance of cells with <2N DNA content, suggesting a mixed response. Therefore, we separated ALL cells into distinct phases of the cell cycle by centrifugal elutriation, labeled cells with 5-ethynyl-2'-deoxyuridine (EdU), and then treated each population with vincristine. Cells isolated during G1 underwent cell death without evidence of EdU uptake, indicating that the cytotoxic effects of vincristine took place during G1 Conversely, cells isolated during S or G2-M phases underwent death following mitotic arrest. Thus, vincristine induces distinct death programs in primary ALL cells depending on cell-cycle phase, and cells in G1 are particularly susceptible to perturbation of interphase microtubules. Primary ALL cells may therefore provide a powerful model system in which to study the multimodal mechanisms underlying MTA-induced cell death. Cancer Res; 76(12); 3553-61. ©2016 AACR. PMID:27197148

  10. Quinuclidine compounds differently act as agonists of Kenyon cell nicotinic acetylcholine receptors and induced distinct effect on insect ganglionic depolarizations.

    PubMed

    Mathé-Allainmat, Monique; Swale, Daniel; Leray, Xavier; Benzidane, Yassine; Lebreton, Jacques; Bloomquist, Jeffrey R; Thany, Steeve H

    2013-12-01

    We have recently demonstrated that a new quinuclidine benzamide compound named LMA10203 acted as an agonist of insect nicotinic acetylcholine receptors. Its specific pharmacological profile on cockroach dorsal unpaired median neurons (DUM) helped to identify alpha-bungarotoxin-insensitive nAChR2 receptors. In the present study, we tested its effect on cockroach Kenyon cells. We found that it induced an inward current demonstrating that it bounds to nicotinic acetylcholine receptors expressed on Kenyon cells. Interestingly, LMA10203-induced currents were completely blocked by the nicotinic antagonist α-bungarotoxin. We suggested that LMA10203 effect occurred through the activation of α-bungarotoxin-sensitive receptors and did not involve α-bungarotoxin-insensitive nAChR2, previously identified in DUM neurons. In addition, we have synthesized two new compounds, LMA10210 and LMA10211, and compared their effects on Kenyon cells. These compounds were members of the 3-quinuclidinyl benzamide or benzoate families. Interestingly, 1 mM LMA10210 was not able to induce an inward current on Kenyon cells compared to LMA10211. Similarly, we did not find any significant effect of LMA10210 on cockroach ganglionic depolarization, whereas these three compounds were able to induce an effect on the central nervous system of the third instar M. domestica larvae. Our data suggested that these three compounds could bind to distinct cockroach nicotinic acetylcholine receptors. PMID:23884575

  11. Inhibitory effects of curcumin on passive cutaneous anaphylactoid response and compound 48/80-induced mast cell activation

    PubMed Central

    Choi, Yun-Ho; Yan, Guang-Hai; Chai, Ok Hee

    2010-01-01

    Mast cells participate in allergies and inflammation by secreting a variety of pro-inflammatory mediators. Curcumin, the active component of turmeric, is a polyphenolic phytochemical with anti-tumor, anti-inflammatory, anti-oxidative, and anti-allergic properties. The effects of curcumin on compound 48/80-induced mast cell activation and passive cutaneous anaphylactoid reactions are unknown. In this report, we investigated the influences of curcumin on the passive cutaneous anaphylactoid response in vivo and compound 48/80-induced mast cell activation in vitro. The mechanism of action was examined by calcium uptake measurements and cAMP assays in mast cells. Curcumin significantly attenuated the mast cell-mediated passive cutaneous anaphylactoid reaction in an animal model. In agreement with this in vivo activity, curcumin suppressed compound 48/80-induced rat peritoneal mast cell (RPMC) degranulation and histamine release from RPMCs. Moreover, compound 48/80-elicited calcium uptake into RPMCs was reduced in a dose-dependent manner by curcumin. Furthermore, curcumin increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced reduction of cAMP in RPMCs. These results corroborate the finding that curcumin may have anti-allergic activity. PMID:21190003

  12. Anti-amyloid compounds protect from silica nanoparticle-induced neurotoxicity in the nematode C. elegans

    PubMed Central

    Scharf, Andrea; Gührs, Karl-Heinz; von Mikecz, Anna

    2016-01-01

    Abstract Identifying nanomaterial-bio-interactions are imperative due to the broad introduction of nanoparticle (NP) applications and their distribution. Here, we demonstrate that silica NPs effect widespread protein aggregation in the soil nematode Caenorhabditis elegans ranging from induction of amyloid in nucleoli of intestinal cells to facilitation of protein aggregation in body wall muscles and axons of neural cells. Proteomic screening revealed that exposure of adult C. elegans with silica NPs promotes segregation of proteins belonging to the gene ontology (GO) group of “protein folding, proteolysis and stress response” to an SDS-resistant aggregome network. Candidate proteins in this group include chaperones, heat shock proteins and subunits of the 26S proteasome which are all decisively involved in protein homeostasis. The pathway of protein homeostasis was validated as a major target of silica NPs by behavioral phenotyping, as inhibitors of amyloid formation rescued NP-induced defects of locomotory patterns and egg laying. The analysis of a reporter worm for serotonergic neural cells revealed that silica NP-induced protein aggregation likewise occurs in axons of HSN neurons, where presynaptic accumulation of serotonin, e.g. disturbed axonal transport reduces the capacity for neurotransmission and egg laying. The results suggest that in C. elegans silica NPs promote a cascade of events including disturbance of protein homeostasis, widespread protein aggregation and inhibition of serotonergic neurotransmission which can be interrupted by compounds preventing amyloid fibrillation. PMID:26444998

  13. Diet-induced and mono-genetic obesity alter volatile organic compound signature in mice.

    PubMed

    Kistler, Martin; Muntean, Andreea; Szymczak, Wilfried; Rink, Nadine; Fuchs, Helmut; Gailus-Durner, Valerie; Wurst, Wolfgang; Hoeschen, Christoph; Klingenspor, Martin; Hrabě de Angelis, Martin; Rozman, Jan

    2016-03-01

    The prevalence of obesity is still rising in many countries, resulting in an increased risk of associated metabolic diseases. In this study we aimed to describe the volatile organic compound (VOC) patterns symptomatic for obesity. We analyzed high fat diet (HFD) induced obese and mono-genetic obese mice (global knock-in mutation in melanocortin-4 receptor MC4R-ki). The source strengths of 208 VOCs were analyzed in ad libitum fed mice and after overnight food restriction. Volatiles relevant for a random forest-based separation of obese mice were detected (26 in MC4R-ki, 22 in HFD mice). Eight volatiles were found to be important in both obesity models. Interestingly, by creating a partial correlation network of the volatile metabolites, the chemical and metabolic origins of several volatiles were identified. HFD-induced obese mice showed an elevation in the ketone body acetone and acrolein, a marker of lipid peroxidation, and several unidentified volatiles. In MC4R-ki mice, several yet-unidentified VOCs were found to be altered. Remarkably, the pheromone (methylthio)methanethiol was found to be reduced, linking metabolic dysfunction and reproduction. The signature of volatile metabolites can be instrumental in identifying and monitoring metabolic disease states, as shown in the screening of the two obese mouse models in this study. Our findings show the potential of breath gas analysis to non-invasively assess metabolic alterations for personalized diagnosis. PMID:26860833

  14. Inhibition of IL-8 gene expression in Caco-2 cells by compounds which induce histone hyperacetylation.

    PubMed

    Huang, N; Katz, J P; Martin, D R; Wu, G D

    1997-01-01

    Ulcerative colitis, an idiopathic inflammatory disease of the colonic mucosa, can be effectively treated by enemas containing short chain fatty acids (SCFA) such as butyrate, propionate, and acetate. The molecular mechanisms that lead to this response have not been well characterized. It is well known that intestinal inflammation leads to an alteration in patterns of epithelial differentiation with an increase in epithelial proliferation and an expansion of cell populations in an undifferentiated state. SCFAs such as butyrate are capable of inhibiting cell proliferation and inducing a differentiated phenotype in vitro. The Caco-2 colon cancer cell line was used to study the effect of SCFAs and the process of cellular differentiation on the expression of the pro-inflammatory cytokine, interleukin 8 (IL-8). SCFAs and trichostatin A, structurally unrelated compounds which both induce histone hyperacetylation, both led to a dose-dependent inhibition of IL-8 gene expression. Furthermore, spontaneous differentiation of Caco-2 cells by growth to a post-confluent state also inhibited the expression of IL-8. A possible mechanism by which SCFAs may be effective in the treatment of ulcerative colitis may be through their ability to increase histone acetylation states and inhibit the production of pro-inflammatory substances by the intestinal epithelium. PMID:9067093

  15. A natural compound, methyl angolensate, induces mitochondrial pathway of apoptosis in Daudi cells.

    PubMed

    Chiruvella, Kishore K; Raghavan, Sathees C

    2011-08-01

    Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested methyl angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt's lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation of nonhomologous DNA end joining pathway in surviving cells. Further, we find that methyl angolensate could induce apoptosis by cell cycle analysis, annexin V-FITC staining, DNA fragmentation and PARP cleavage. Besides, MA treatment led to reactive oxygen species generation and loss of mitochondrial transmembrane potential. These results suggest the activation of mitochondrial pathway of apoptosis. Hence, we identify MA as a potential chemotherapeutic agent against Daudi cells. PMID:20169399

  16. Simulations of airglow variations induced by the CO2 increase and solar cycle variation from 1980 to 1991

    NASA Astrophysics Data System (ADS)

    Huang, Tai-Yin

    2016-09-01

    Airglow intensity and Volume Emission Rate (VER) variations induced by the increase of CO2 gas concentration and F10.7 variation (used as a proxy for the 11-year solar cycle variation) were investigated for the period from 1980 to 1991, encompassing a full solar cycle. Two airglow models are used to simulate the induced variations of O(1S) greenline, O2(0,1) atmospheric band , and OH(8,3) airglow for this study. The results show that both the airglow intensities and peak VERs correlate positively with the F10.7 solar cycle variation and display a small linear trend due to the increase of CO2 gas concentration. The solar-cycle induced airglow intensity variations show that O(1S) greenline has the largest variation (~26%) followed by the O2(0,1) atmospheric band (~23%) and then OH(8,3) airglow (~8%) over the 11 year timespan. The magnitudes of the induced airglow intensity variations by the increase of CO2 gas concentration are about an order of magnitude smaller than those by the F10.7 solar cycle variation. In general, the F10.7 solar cycle variation and CO2 increase do not seem to systematically alter the VER peak altitude of the airglow emissions, though the OH(8,3) VER peak altitude moves up slightly during the years when the F10.7 value falls under 100 SFU.

  17. Respiratory syncytial virus matrix protein induces lung epithelial cell cycle arrest through a p53 dependent pathway.

    PubMed

    Bian, Tao; Gibbs, John D; Örvell, Claes; Imani, Farhad

    2012-01-01

    Respiratory syncytial virus (RSV) is the major cause of viral respiratory infections in children. Our previous study showed that the RSV infection induced lung epithelial cell cycle arrest, which enhanced virus replication. To address the mechanism of RSV-induced cell cycle arrest, we examined the contribution of RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M protein caused the cells to proliferate at a slower rate than in control cells. The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549 cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M expression induced p53 and p21 accumulation and decreased phosphorylation of retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle arrest was restored after transfection of p53 cDNA into H1299 cells. Taken together, these results indicate that RSV-M protein regulates lung epithelial cell cycle through a p53-dependent pathway, which enhances RSV replication. PMID:22662266

  18. The effect of topically applied salicylic compounds on serotonin-induced scratching behaviour in hairless rats.

    PubMed

    Thomsen, J S; Simonsen, L; Benfeldt, E; Jensen, S B; Serup, J

    2002-08-01

    There is a strong need for antipruritic substances for treating itch in clinical dermatology. In one recent human study, topically applied acetylsalicylic acid has been described to rapidly decrease histamine-induced itch. We have established a model for periferally elicited pruritus by injecting serotonin into the rostral back area (neck) in rats. Using this model, we aimed to investigate the antipruritic potential of four different salicylic compounds, which all possess different skin penetration characteristics. Eighteen rats were studied for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 micro l), 10 micro l of test substances was applied to a circular area 18 mm in diameter. The four substances were salicylic acid, butyl salicylate, diethylamine salicylate and salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5% w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly absorbed through rat skin in contrast to salicylic acid and butyl salicylate. After serotonin injections, scratching was monitored by video recording for 1.5 h. Compared with the vehicle, a lower number of scratch sequences were seen when diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been applied. The numbers of scratch sequences were lower with diethylamine salicylate and salicylamide than with the vehicle throughout the 1.5-h study period. We conclude that topical application of diethylamine salicylate and salicylamide could suppress serotonin-induced scratching in rats. The antipruritic effect seems to be related to the slow drug release of the two substances. The results may be clinically relevant as serotonin induces itch in humans. PMID:12190947

  19. A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

    PubMed Central

    Park, Dongsun; Jo, In Geun; Jang, Ja Young; Kwak, Tae Hwan; Yoo, Sang Ku; Jeon, Jeong Hee; Choi, Ehn-Kyoung; Joo, Seong Soo; Kim, Okjin; Kim, Yun-Bae

    2015-01-01

    The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents. PMID:26336585

  20. A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis.

    PubMed

    Park, Dongsun; Jo, In Geun; Jang, Ja Young; Kwak, Tae Hwan; Yoo, Sang Ku; Jeon, Jeong Hee; Choi, Ehn-Kyoung; Joo, Seong Soo; Kim, Okjin; Kim, Yun-Bae

    2015-09-01

    The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents. PMID:26336585

  1. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma

    PubMed Central

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-01-01

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10–20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy. PMID:26694364

  2. Synthesis, characterization, cytotoxicity, a poptosis and cell cycle arrest of dibenzoxanthenes derivatives

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Zhen; Yao, Jun-Hua; Jiang, Guang-Bin; Wang, Ji; Huang, Hong-Liang; Liu, Yun-Jun

    2014-12-01

    Two new dibenzoxanthenes compounds 1 and 2 have been synthesized and characterized by analytical and spectral methods. The crystal structure of compound 2 informs that the five rings of compound are almost planar. The DNA binding properties of two compounds were studied by absorption titration, viscosity measurement and luminescence. These results indicate that two compounds interact with calf thymus DNA through intercalative mode. Agarose gel electrophoresis experiment shows that PBR 322 DNA can be induced to cleave by two compounds under photoactivated condition. Compound 1 exhibits higher cytotoxicity than compound 2 toward MG-63, BEL-7402 and A549 cells. The apoptosis and cellular uptake of MG-63 cells were studied by fluorescence microscopy. Two compounds can also enhance the level of reactive oxygen species (ROS) and decrease the mitochondrial membrane potential. Compound 1 induces cell cycle arrest in G2/M phase and compound 2 induces cell cycle arrest in G0/G1 phase in MG-63.

  3. Advanced heat pump for the recovery of volatile organic compounds. Phase 1, Conceptual design of an advanced Brayton cycle heat pump for the recovery of volatile organic compounds: Final report

    SciTech Connect

    Not Available

    1992-03-01

    Emissions of Volatile Organic Compounds (VOC) from stationary industrial and commercial sources represent a substantial portion of the total US VOC emissions. The ``Toxic-Release Inventory`` of The US Environmental Protection Agency estimates this to be at about 3 billion pounds per year (1987 estimates). The majority of these VOC emissions are from coating processes, cleaning processes, polymer production, fuel production and distribution, foam blowing,refrigerant production, and wood products production. The US Department of Energy`s (DOE) interest in the recovery of VOC stems from the energy embodied in the recovered solvents and the energy required to dispose of them in an environmentally acceptable manner. This Phase I report documents 3M`s work in close working relationship with its subcontractor Nuclear Consulting Services (Nucon) for the preliminary conceptual design of an advanced Brayton cycle heat pump for the recovery of VOC. Nucon designed Brayton cycle heat pump for the recovery of methyl ethyl ketone and toluene from coating operations at 3M Weatherford, OK, was used as a base line for the work under cooperative agreement between 3M and ODE. See appendix A and reference (4) by Kovach of Nucon. This cooperative agreement report evaluates and compares an advanced Brayton cycle heat pump for solvent recovery with other competing technologies for solvent recovery and reuse. This advanced Brayton cycle heat pump is simple (very few components), highly reliable (off the shelf components), energy efficient and economically priced.

  4. Characterization and quenching of friction-induced limit cycles of electro-hydraulic servovalve control systems with transport delay.

    PubMed

    Wang, Yuan-Jay

    2010-10-01

    This paper develops a systematic and straightforward methodology to characterize and quench the friction-induced limit cycle conditions in electro-hydraulic servovalve control systems with transport delay in the transmission line. The nonlinear friction characteristic is linearized by using its corresponding describing function. The delay time in the transmission line, which could accelerate the generation of limit cycles is particularly considered. The stability equation method together with parameter plane method provides a useful tool for the establishment of necessary conditions to sustain a limit cycle directly in the constructed controller coefficient plane. Also, the stable region, the unstable region, and the limit cycle region are identified in the parameter plane. The parameter plane characterizes a clear relationship between limit cycle amplitude, frequency, transport delay, and the controller coefficients to be designed. The stability of the predicted limit cycle is checked by plotting stability curves. The stability of the system is examined when the viscous gain changes with respect to the temperature of the working fluid. A feasible stable region is characterized in the parameter plane to allow a flexible choice of controller gains. The robust prevention of limit cycle is achieved by selecting controller gains from the asymptotic stability region. The predicted results are verified by simulations. It is seen that the friction-induced limit cycles can be effectively predicted, removed, and quenched via the design of the compensator even in the case of viscous gain and delay time variations unconditionally. PMID:20542269

  5. Tetrandrine induces G1/S cell cycle arrest through the ROS/Akt pathway in EOMA cells and inhibits angiogenesis in vivo.

    PubMed

    Xiao, Wenkai; Jiang, Yajie; Men, Qiuxu; Yuan, Ling; Huang, Zebo; Liu, Ting; Li, Wenhua; Liu, Xin

    2015-01-01

    Tetrandrine, a bisbenzylisoquinoline alkaloid, is known to inhibit tumor cell proliferation and induce apoptosis in cancer models in vitro and in vivo. In the present study, tetrandrine significantly inhibited the proliferation of mouse endothelial cells (EOMA cell) and induced G1/S arrest in EOMA cells, in which the expressions of cyclin D and cyclin E and CDKs were downregulated. Tetrandrine treatment also caused intracellular accumulation of reactive oxygen species (ROS). Pretreatment with NAC, which is a ROS inhibitor, blocked G1/S cell arrest and cyclin regulation induced by tetrandrine, implying that ROS generation plays an important role in tetrandrine-induced cell cycle arrest. Furthermore, a decreased phospho-Akt protein level after tetrandrine treatment was reversible with the removal of the intracellular ROS by NAC. Notably, overexpression of Akt decreased tetrandrine-induced G1/S arrest. Finally, we verified the antiangiogenic effects of tetrandrine in vivo in a liver cancer xenograft model in nude mice. In conclusion, tetrandrine inhibits EOMA cell growth through the ROS/Akt pathway, and it could be a promising compound for cancer therapy as an inhibitor of tumor vascular growth. PMID:25355542

  6. Antibacterial active compounds from Hypericum ascyron L. induce bacterial cell death through apoptosis pathway.

    PubMed

    Li, Xiu-Mei; Luo, Xue-Gang; Si, Chuan-Ling; Wang, Nan; Zhou, Hao; He, Jun-Fang; Zhang, Tong-Cun

    2015-01-01

    Hypericum ascyron L. has been used as a traditional medicine for the treatment of wounds, swelling, headache, nausea and abscesses in China for thousands of years. However, modern pharmacological studies are still necessary to provide a scientific basis to substantiate their traditional use. In this study, the mechanism underlying the antimicrobial effect of the antibacterial activity compounds from H. ascyron L. was investigated. Bioguided fractionation of the extract from H. ascyron L. afforded antibacterial activity fraction 8. The results of cup plate analysis and MTT assay showed that the MIC and MBC of fraction 8 is 5 mg/mL. Furthermore, using Annexin V-FITC/PI, TUNEL labeling and DNA gel electrophoresis, we found that cell death with apoptosis features similar to those in eucaryon could be induced in bacteria strains after exposure to the antibacterial activity compounds from H. ascyron L. at moderate concentration. In addition, we further found fraction 8 could disrupt the cell membrane potential indicate that fraction 8 exerts pro-apoptotic effects through a membrane-mediated apoptosis pathway. Finally, quercetin and kaempferol 3-O-β-(2″-acetyl)-galactopyranoside, were identified from fraction 8 by means of Mass spectrometry and Nuclear magnetic resonance. To our best knowledge, this study is the first to show that Kaempferol 3-O-β-(2″-acetyl)-galactopyranoside coupled with quercetin had significant antibacterial activity via apoptosis pathway, and it is also the first report that Kaempferol 3-O-β-(2″-acetyl)-galactopyranoside was found in clusiacea. Our data might provide a rational base for the use of H. ascyron L. in clinical, and throw light on the development of novel antibacterial drugs. PMID:25916905

  7. Static mechanical strain induces capillary endothelial cell cycle re-entry and sprouting.

    PubMed

    Zeiger, A S; Liu, F D; Durham, J T; Jagielska, A; Mahmoodian, R; Van Vliet, K J; Herman, I M

    2016-01-01

    Vascular endothelial cells are known to respond to a range of biochemical and time-varying mechanical cues that can promote blood vessel sprouting termed angiogenesis. It is less understood how these cells respond to sustained (i.e., static) mechanical cues such as the deformation generated by other contractile vascular cells, cues which can change with age and disease state. Here we demonstrate that static tensile strain of 10%, consistent with that exerted by contractile microvascular pericytes, can directly and rapidly induce cell cycle re-entry in growth-arrested microvascular endothelial cell monolayers. S-phase entry in response to this strain correlates with absence of nuclear p27, a cyclin-dependent kinase inhibitor. Furthermore, this modest strain promotes sprouting of endothelial cells, suggesting a novel mechanical 'angiogenic switch'. These findings suggest that static tensile strain can directly stimulate pathological angiogenesis, implying that pericyte absence or death is not necessarily required of endothelial cell re-activation. PMID:27526677

  8. Cryogenic hydrogen-induced air-liquefaction technologies for combined-cycle propulsion applications

    NASA Technical Reports Server (NTRS)

    Escher, William J. D.

    1992-01-01

    Given here is a technical assessment of the realization of cryogenic hydrogen induced air liquefaction technologies in a prospective onboard aerospace vehicle process setting. The technical findings related to the status of air liquefaction technologies are reviewed. Compact lightweight cryogenic heat exchangers, heat exchanger atmospheric constituent fouling alleviation measures, para/ortho-hydrogen shift-conversion catalysts, cryogenic air compressors and liquid air pumps, hydrogen recycling using slush hydrogen as a heat sink, liquid hydrogen/liquid air rocket-type combustion devices, and technically related engine concepts are discussed. Much of the LACE work is related to aerospaceplane propulsion concepts that were developed in the 1960's. Emphasis is placed on the Liquid Air Cycle Engine (LACE).

  9. Curcumin loaded PLGA-poloxamer blend nanoparticles induce cell cycle arrest in mesothelioma cells.

    PubMed

    Mayol, Laura; Serri, Carla; Menale, Ciro; Crispi, Stefania; Piccolo, Maria Teresa; Mita, Luigi; Giarra, Simona; Forte, Maurizio; Saija, Antonina; Biondi, Marco; Mita, Damiano Gustavo

    2015-06-01

    The pharmacological potential of curcumin (CURC) is severely restricted because of its low water solubility/absorption, short half-life and poor bioavailability. To overcome these issues, CURC-loaded nanoparticles (NPs) were produced by a double emulsion technique. In particular, NPs were made up of an amphiphilic blend of poloxamers and PLGA to confer stealth properties to the NPs to take advantage of the enhanced permeability and retention (EPR) effect. Different surface properties of NPs made up of bare PLGA and PLGA/poloxamer blend were confirmed by the different interactions of these NPs with serum proteins and also by their ability to be internalized by mesothelioma cell line. The uptake of PLGA/poloxamer NPs induces a persistent block in G0/G1 phase of the cell cycle up to 72 h, thus overcoming the drug tolerance phenomenon, normally evidenced with free CURC. PMID:25794477

  10. Freeze-Thaw Cycling Induced Isotropic-Nematic Coexistence of Amyloid Fibrils Suspensions.

    PubMed

    Zhao, Jianguo; Bolisetty, Sreenath; Adamcik, Jozef; Han, Jun; Fernández-Ronco, María P; Mezzenga, Raffaele

    2016-03-15

    Amyloid fibrils are charged semiflexible assemblies with very large aspect ratio (length to diameter, L/D). Because of this large aspect ratio, the isotropic (I) and nematic (N) phase coexistence expected from the first-order thermodynamic nature of the I-N phase transition, as predicted from the Onsager's theory, is vanishingly small and, in practice, challenging to experimentally observe. In this study we present a remarkable widening of the I + N biphasic region in β-lactoglobulin fibrils suspension via freeze-thaw (F-T) cycling. The demixing behavior can be induced and controlled by a slow growth of propagation front of the ice crystals, which grow by excluding the amyloid fibrils from the crystal phase and thus concentrating them in the liquid phase. The growth of the ice crystals is accompanied by the formation of concentrated and elongated tactoid-like structure in the liquid phase. During the subsequent thawing cycling, at large tactoid domains, the mismatch in density caused by the presence of amyloid fibrils is sufficient to generate a sedimentation of the N phase at the bottom of the vial, coexisting with an I phase on the top. We reason why, despite the remarkable stability of the coexisting I and N phases observed over several weeks after F-T cycling, the biphasic region is understood to be a nonequilibrium, metastable state. Yet, the results in this study suggest that the F-T treatment is an effective approach to stabilize multiphase coexistence of liquid crystalline phases in colloidal suspensions of anisotropic particles without the need of additives, such as depleting agents, needed to modify interaction potentials. PMID:26907697