A nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract has exhibited anticancer activity in vitro and in vivo in a number of cancer cell lines. We investigated the ...effect of NM on human leukemic myeloid U-937 cells in vitro by measuring: cell proliferation, MMP expression, invasion, apoptosis, and COX-2 and COX-1 protein expression.
Human leukemic cell line U-937 (ATCC) was cultured in RPMI medium supplemented with fetal bovine serum and antibiotics. After 24 h, the cells were treated with NM at 0, 50, 100, 250, 500 and 1000 Ојg/ml, in triplicate at each dose. Phorbol 12-myristate 13-acetate (PMA), 100 ng/ml was added to cells to induce MMP-9 secretion. Cell proliferation was evaluated by MTT assay, MMP expression by gelatinase zymography, invasion through Matrigel, apoptosis by using live green caspase detection kit (Molecular Probe), and COX-2 and COX-1 expression by Western blot.
NM had no effect on U-937 cell growth at a concentration of 250 Ојg/ml and exhibited an antiproliferative effect at 500 Ојg/ml concentration. Zymography did not demonstrate MMP-2 or MMP-9 secretion in normal cells; however, PMA strongly induced MMP-9, which was inhibited by NM in a dose-dependent manner. Cell penetration through Matrigel was significantly reduced (by 95%) at 250 Ојg/ml NM and completely blocked at 500 Ојg/ml NM. NM induced slight apoptosis at 100 Ојg/ml and moderate at 500 and 1000 Ојg/ml concentration. NM inhibited COX-2 expression in a dose-dependent fashion and had no effect on COX-1 expression.
Our results suggest that NM has potent inhibitory effects on U-937 cell growth and expression of inflammatory mediators, significant parameters in AML progression.
influenza, one of the oldeist and most common infections, poses a serious health problem causing significant morbidity and mortality, and imposing substantial economic costs. The efficacy of current ...drugs is limited and improved therapies are needed. A unique nutrient mixture (NM), containing ascorbic acid, green tea extract, lysine, proline, N‐acetyl cysteine, selenium among other micronutrients, has been shown to exert anti‐carcinogenic and anti‐atherogenic activity both in vitro and in vivo. Many of the constituents of NM have been shown to have an inhibitory effect on replication of influenza virus and HIV. This prompted us to study the effect of NM on influenza A virus multiplication in infected cells and neuraminidase activity (NA) in virus particles. Addition of NM to Vero or MDCK cells post infection resulted in dose‐dependent inhibition of viral nucleoprotein (NP) production in infected cells. NM‐mediated inhibition of viral NP was selective and not due to cytotoxicity towards host cells. This antiviral effect was enhanced by pretreatment of virus with the nutrient mixture. Individual components of NM, namely ascorbic acid and green tea extract, also blocked viral NP production, conferring enhanced inhibition when tested in combination. Incubation of cell‐free virus with NM resulted in dose‐dependent inhibition of associated NA enzyme activity. In conclusion, the nutrient mixture exerts an antiviral effect against influenza A virus by lowering viral protein production in infected cells and diminishing viral enzymatic activity in cell‐free particles.
Long-term survival of patients with hepatocellular carcinoma (HCC), a common cancer worldwide, remains poor, due to metastasis and recurrence.
To investigate the effect of a novel nutrient mixture ...(NM) containing ascorbic acid, lysine, proline, and green tea extract on human HCC cell line Sk-Hep-1 In vivo and In vitro.
After one week of isolation, 5-6 week old male athymic nude mice were inoculated with 3 x 10(6) SK-Hep-1 cells subcutaneously and randomly divided into two groups; group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighed and processed for histology. We also tested the effect of NM In vitro on SK-Hep-1 cells, measuring cell proliferation by MTT assay, invasion through Matrigel, apoptosis by green caspase detection kit, MMP secretion by zymography, and morphology by H&E staining.
NM inhibited tumor weight and burden of SK-Hep-1 xenografts by 42% and 33% respectively. In vitro , NM exhibited 33% toxicity over the control at 500 and 1,000 microg/ml concentration. Zymography demonstrated MMP-2 and MMP-9 secretion which was inhibited by NM in a dose dependent fashion, with virtual total inhibition at 1000 microg/ml. Invasion through Matrigel was inhibited at 100, 500 and 1,000 microg/ml by 53%, 83% and 100% respectively. NM induced slight apoptosis at 100 microg/ml, and profound apoptosis at 500 microg/ml and 1000 microg/ml concentration.
These results suggest that NM has therapeutic potential in treatment of HCC.
X-rays produced by compact flares corotating with a Keplerian accretion disc are modulated in time by Doppler effects. We improve on previous calculations of these effects by considering recent ...models of intrinsic X-ray variability, and we compute the expected strength of the relativistic signal in current data of Seyfert galaxies and black hole binaries. Such signals can clearly be seen in, for example, recent XMM–Newton data from MCG–6-30-15, if indeed the X-rays are produced by corotating flares concentrated toward the inner disc edge around an extreme Kerr black hole. The lack of the signal in the data collected so far gives support to models where the X-ray sources in active galaxies do not follow Keplerian orbits close to the black hole.
We investigate possible sky survey modes with the Middle Sized Telescopes (MST, aimed at covering the energy range from ∼100GeV to 10TeV) subsystem of the Cherenkov Telescope Array (CTA). We use the ...standard CTA tools, CORSIKA and sim_telarray, to simulate the development of gamma-ray showers, proton background and the telescope response. We perform simulations for the H.E.S.S.-site in Namibia, which is one of the candidate sites for the CTA experiment. We study two previously considered modes, parallel and divergent, and we propose a new, convergent mode with telescopes tilted toward the array center. For each mode we provide performance parameters crucial for choosing the most efficient survey strategy. For the non-parallel modes we study the dependence on the telescope offset angle. We show that use of both the divergent and convergent modes results in potential advantages in comparison with use of the parallel mode. The fastest source detection can be achieved in the divergent mode with larger offset angles (∼6° from the field of view center for the outermost telescopes), for which the time needed to perform a scan at a given sensitivity level is shorter by a factor of ∼2.3 than for the parallel mode. We note, however, the direction and energy reconstruction accuracy for the divergent mode is even by a factor of ∼2 worse than for other modes. Furthermore, we find that at high energies and for observation directions close to the center of the array field of view, the best performance parameters are achieved with the convergent mode, which favors this mode for deep observations of sources with hard energy spectra.
Leukemia is characterized by uncontrolled marrow cell proliferation and metastatic foci. We investigated the antitumor potential of a nutrient mixture on malignant leukemia P-388 cells.
The nutrient ...mixture containing lysine, proline, ascorbic acid, green tea extract and other nutrients is formulated to target key pathways in cancer progression. The cells were treated with the mixture, and tested at doses 0, 10, 50, 100, 500 and 1000 μg/ml in triplicates. The effects were evaluated by cell proliferation, Matrigel invasion, cell morphology and apoptosis. The in vivo effect was measured in male nude mice (n = 12) inoculated with P-388 cells. After randomly dividing in two groups, each group was fed regular and the nutrient mixture supplemented diet and the mice were sacrificed after four weeks.
The nutrient mixture decreased P-388 cell proliferation at 500 and 1000 μg/ml. Only 10% cells were viable at 1000 μg/ml. Matrigel invasion was significantly inhibited in a dose dependent manner with virtually total inhibition at 1000 μg/ml. Cell morphological features notably changed with dose increase to 1000 μg/ml. Analysis of apoptotic cells on live green caspase kit exhibited gradual increase with the increasing dose of the nutrient mixture, and at 1000 μg/ ml 92% of P-388 cells were in late apoptosis. Tumors in the group of mice supplemented with the nutrient mixture had 50% lower weight compared to the tumors in control group (p = 0.0105). Histopathologically, both the groups of tumors were similar, yet size of tumors in the group treated with the nutrient mixture was considerably smaller.
These results indicate that the nutrient mixture exhibited significant action against multiple targets in P-388 leukemia and may have potential in human leukemia.
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent a series of upgrades, involving the ...exchange of the MAGIC-I camera and its trigger system, as well as the upgrade of the readout system of both telescopes. We use observations of the Crab Nebula taken at low and medium zenith angles to assess the key performance parameters of the MAGIC stereo system. For low zenith angle observations, the standard trigger threshold of the MAGIC telescopes is ∼ 50GeV. The integral sensitivity for point-like sources with Crab Nebula-like spectrum above 220GeV is (0.66 ± 0.03)% of Crab Nebula flux in 50h of observations. The angular resolution, defined as the σ of a 2-dimensional Gaussian distribution, at those energies is ≲ 0.07°, while the energy resolution is 16%. We also re-evaluate the effect of the systematic uncertainty on the data taken with the MAGIC telescopes after the upgrade. We estimate that the systematic uncertainties can be divided in the following components: < 15% in energy scale, 11%–18% in flux normalization and ± 0.15 for the energy spectrum power-law slope.
ABSTRACT
We present a measurement of the extragalactic background light (EBL) based on a joint likelihood analysis of 32 gamma-ray spectra for 12 blazars in the redshift range z = 0.03–0.944, ...obtained by the MAGIC telescopes and Fermi-LAT. The EBL is the part of the diffuse extragalactic radiation spanning the ultraviolet, visible, and infrared bands. Major contributors to the EBL are the light emitted by stars through the history of the Universe, and the fraction of it that was absorbed by dust in galaxies and re-emitted at longer wavelengths.
The EBL can be studied indirectly through its effect on very high energy photons that are emitted by cosmic sources and absorbed via γγ interactions during their propagation across cosmological distances. We obtain estimates of the EBL density in good agreement with state-of-the-art models of the EBL production and evolution. The 1σ upper bounds, including systematic uncertainties, are between 13 per cent and 23 per cent above the nominal EBL density in the models. No anomaly in the expected transparency of the Universe to gamma-rays is observed in any range of optical depth. We also perform a wavelength-resolved EBL determination, which results in a hint of an excess of EBL in the 0.18–0.62 $\mu\mathrm{ m}$ range relative to the studied models, yet compatible with them within systematics.
Untreated acute promyelocytic leukemia is the most malignant form of acute leukemias, with median survival of less than one month. We investigated in vitro and in vivo synergistic effects of a ...nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract, on acute promyelocytic leukemia HL-60 cells.
In vitro, the HL-60 cells were cultured and exposed to NM at doses 0-1000 μg/ml. Cell viability was assessed by Trypan blue dye exclusion test, matrix metalloproteinases (MMP) expression by gelatinase zymography, invasion through Matrigel and apoptosis by live green Poly Caspase Detection Kit. In vivo studies were carried out in athymic nude mice subcutaneously inoculated with HL-60 cells.
In vitro, NM exhibited a dose dependent reduction in cells viability. Zymography revealed matrix MMP-2 and phorbol 12-myristate 13-acetate induced MMP-9 expression. NM inhibited expression of both MMP in a dose dependent manner. Similar step-wise reduction in the Matrigel invasion by HL-60 cells was also observed by this combination with incremental doses. Gradually increasing doses of NM induced significant apoptosis in HL-60 cells. In vivo, NM inhibited tumor growth by 50%.
The results indicate that NM significantly suppresses tumor growth, decreases cell viability, inhibits MMP expression, Matrigel invasion and induces apoptosis in HL-60 cells.
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