In vitro investigation of antitumor and antimicrobial activities of extracts of mahonia, Mahonia aquifolium (Pursh) Nutt.

Na osnovu podataka o upotrebi vrste Mahonia aquifolium u tradicionalnoj medicini definisan je cilj našeg istraživanja, ispitivanje antitumorske i antimikrobne aktivnosti ekstrakata kore mahonije. Ispitivanjem citotoksičnosti vodenog i etanolnog ekstrakta na humanim malignim ćelijskim linijama je dokazano da ekstrakti imaju selektivnu citotoksičnu aktivnost, a najviši intenzitet dejstva su pokazali na HeLa ćelijama adenokarcinoma cerviksa. Fluorescentnom mikroskopijom i analizom faza ćelijskog ciklusa je pokazano da ekstrakti indukuju apoptozu u HeLa ćelijama. Primenom inhibitora kaspaza pokazano je da ekstrakti indukuju apoptozu preko spoljašnjeg puta aktivacije. Ispitivanja na endotelijalnim EA.hy926 ćelijama pokazala su antiangiogenetski i antimigratorni efekat ekstrakata. Primena tretmana doksorubicin/ekstrakt ukazala je na izraženo sinergističko dejstvo ekstrakta sa doksorubicinom na A549 ćelijama karcinoma pluća. Ekstrakti povećavaju zadržavanje leka u ćeliji i pojačavaju efekat doksorubicina na smanjenje migracije A549 ćelija i njihovo grupisanje u kolonije. Antimetastatski potencijal kombinacije doksorubicin/ekstrakt potvrđen je analizom ekspresije gena odgovornih za invazivnost. Oba ekstrakta ispoljavaju antimikrobni efekat, koji je najizraženiji na bakterijskoj vrsti Staphylococcus aureus. Ekstrakti dovode do smanjenja produkcije biofilma i glikokaliksa. Sa antibioticima i antimikoticima ekstrakti su delovali sinergistički. Hemijskom analizom potvrđeno je da su za aktivnost ekstrakata M. aquifolium odgovorni alkaloidi tipa berberina. Na intenzitet citotoksičnosti najviše utiču berberin, palmatin i berbamin. Rezultati su pokazali da M. aquifolium može naći svoje mesto u terapiji malignih ili infektivnih oboljenja, pojedinačno i u kombinaciji sa postojećim lekovima.The goal of our research was investigation of antitumor and antimicrobial activities of Mahonia aquifolium extracts and it was based on its use in traditional medicine. Water and ethanol extract exerted selective cytotoxic activity on examined malignant cell lines, and the best activity was observed against cervical adenocarcinoma, HeLa, cells. Fluorescence microscopy and cell cycle analysis showed that both extracts induce apoptosis in HeLa cells. Experiments with caspase inhibitors showed that extracts induce a caspase-dependent apoptosis through extrinsic pathway. Both extracts inhibit the migration of EA.hy926 cells, and exerted anti-angiogenic effect. The investigation of the doxorubicine/extract treatment showed synergistic effect of extracts with doxorubicine against lung carcinoma A549, cells. Extracts were shown to prolong doxorubicin retention time in A549 cells. A549 cells treated with doxorubicin/extract were shown to have lower migratory and colony formation potentials than the cells treated with doxorubicin alone. Antimetastatic effect of the treatment was confirmed with analysis of expression of genes responsible for malignant cells invasiveness. Extracts exerted antimicrobial effect. The best effect was observed against Staphylococcus aureus. Extracts showed potential to inhibit production of biofilm and glycocalycs. The use of extracts with antibiotics and antimycotics showed synergistic effect. Chemical analysis confirmed that berberine type alkaloids are the most responsible for activities of M. aquifolium. The compounds with the highest cytotoxic activity are: berberine, palmatine, and berbamine. The results of our research suggested that M. aquifolium may be used in therapy of malignant or infective diseases, alone or in combination with other drugs

Supplementary data for article: Pantelić, N. Đ.; Zmejkovski, B. B.; Trifunović-Macedoljan, J.; Savić, A.; Stanković, D.; Damjanović, A.; Juranic, Z.; Kaluđerović, G. N.; Sabo, T. Gold(III) Complexes with Esters of Cyclohexyl-Functionalized Ethylenediamine-N,N ’-Diacetate. Journal of Inorganic Biochemistry 2013, 128, 146–153. https://doi.org/10.1016/j.jinorgbio.2013.08.002

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2013.08.002]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1422

Excitons in a Photosynthetic Light-Harvesting System: A Combined Molecular Dynamics/Quantum Chemistry and Polaron Model Study

The dynamics of pigment-pigment and pigment-protein interactions in light-harvesting complexes is studied with a novel approach which combines molecular dynamics (MD) simulations with quantum chemistry (QC) calculations. The MD simulations of an LH-II complex, solvated and embedded in a lipid bilayer at physiological conditions (with total system size of 87,055 atoms) revealed a pathway of a water molecule into the B800 binding site, as well as increased dimerization within the B850 BChl ring, as compared to the dimerization found for the crystal structure. The fluctuations of pigment (B850 BChl) excitation energies, as a function of time, were determined via ab initio QC calculations based on the geometries that emerged from the MD simulations. From the results of these calculations we constructed a time-dependent Hamiltonian of the B850 exciton system from which we determined the linear absorption spectrum. Finally, a polaron model is introduced to describe quantum mechanically both the excitonic and vibrational (phonon) degrees of freedom. The exciton-phonon coupling that enters into the polaron model, and the corresponding phonon spectral function are derived from the MD/QC simulations. It is demonstrated that, in the framework of the polaron model, the absorption spectrum of the B850 excitons can be calculated from the autocorrelation function of the excitation energies of individual BChls, which is readily available from the combined MD/QC simulations. The obtained result is in good agreement with the experimentally measured absorption spectrum.Comment: REVTeX3.1, 23 pages, 13 (EPS) figures included. A high quality PDF file of the paper is available at http://www.ks.uiuc.edu/Publications/Papers/PDF/DAMJ2001/DAMJ2001.pd

Physicochemical characterisation of pottery from the Vinca culture, Serbia, regarding the firing temperature and decoration techniques

A study of decorated Neolithic pottery samples from the excavation site Plocnik, Serbia, was performed using X-ray powder diffraction (XRPD), Fourier transform infrared (FTIR) and X-ray fluorescence (XRF) spectroscopy. The investigated samples belong to the era of the Vinca culture that existed in the central Balkan region from the mid VI until the first half of the V millennium BCE. The mineralogical composition of the pottery samples and comparison of the investigated pottery with thermally treated local clay indicated firing temperatures in the range from 600 to 800 degrees C. Two different types of white pigments were identified in white incrusted decorations: calcium carbonate and bone white (composed of crushed bones). This is the first evidence of the use of bones for decorations in pottery of the Vinca culture from the excavation site Plocnik. In addition to this, it was revealed that the potters used the iron reduction technique for obtaining black decorations

Spectroscopic investigation of two Serbian icons painted on canvas

A multianalytical study of two Serbian icons, The Virgin and Child and St. Petka, painted on canvas by unknown authors was performed in order to identify the materials used as pigments, binders and the ground layer. The investigated icons belong to the Museum of the Serbian Orthodox Church in Belgrade. Samples, collected from different parts of the icons, were analysed by: optical microscopy (OM), energy dispersive X-Ray fluorescence (EDXRF), Fourier transform infrared (FTIR) and micro-Raman spectroscopy. The obtained results revealed the presence of the following pigments: Prussian Blue, ultramarine, Green Earth, iron oxides, Lead White and Zinc White. Linseed oil was used as the binder. The materials used for the ground layers were gypsum, calcite, baryte and Lead White. The gilded surface of the icon The Virgin and Child was made of gold. The gilded surface on the frame of this icon was made of imitation of gold, i.e., Schlagmetal, since EDXRF spectroscopy showed the presence of copper and zinc, while gold was not detected. Based on the style and the consideration of an art historian, as well as on the obtained results for the corresponding pigments and binder, both icons were most probably made at the end of 19th or the beginning of the 20th century

Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms

The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34(+) cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV) and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF) patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET) and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34(+) cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs

Slow Magnetic Relaxation and Single-Molecule Toroidal Behaviour in a Family of Heptanuclear {CrIIILnIII6} (Ln=Tb, Ho, Er) Complexes

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. The synthesis, magnetic properties, and theoretical studies of three heterometallic {Cr III Ln III 6 } (Ln=Tb, Ho, Er) complexes, each containing a metal topology consisting of two Ln 3 triangles connected via a Cr III linker, are reported. The {CrTb 6 } and {CrEr 6 } analogues display slow relaxation of magnetization in a 3000 Oe static magnetic field. Single-crystal measurements reveal opening up of the hysteresis loop for {CrTb 6 } and {CrHo 6 } molecules at low temperatures. Ab initio calculations predict toroidal magnetic moments in the two Ln 3 triangles, which are found to couple, stabilizing a con-rotating ferrotoroidal ground state in Tb and Ho examples and extend the possibility of observing toroidal behaviour in non Dy III complexes for the first time

Synthesis, cytotoxicity and computational study of novel protoberberine derivatives

A novel and efficient synthetic route was developed for the preparation of protoberberine derivatives. A methodology, designed primarily to control the substitution patterns on the terminal rings, was used to access a small array of these compounds. An initial biological profiling suggested an anticancer potential of the synthesised derivatives, while structure-based target fishing identified their potential targets and established a rational basis for further structural modifications. Although the activities need further improvement, the study demonstrated that the described approach may be useful in the discovery of novel lead compounds

New Results on Pb-Au Collisions at 40 AGeV from the CERES/NA45 Experiment

In 1999 the CERES/NA45 ran at the CERN SPS with a beam energy of 40 GeV/nucleon. The data set comprises about 8.7 millions Pb-Au events with a trigger selection corresponding to approximately the most central 30% of the geometrical cross section. Results on low-mass electron pair analysis are presented. The upgrade of the experimental setup with the radial drift TPC has allowed to enhance hadron physics capabilities of the experiment. New results on hadron spectra (including Lambda) and flow are presented.Comment: Talk at the International Nuclear Physics Conference INPC2001, Berkeley, CA, July 29th - August 3rd 200

Universal Pion Freeze-out in Heavy-Ion Collisions

Based on an evaluation of data on pion interferometry and on particle yields at mid-rapidity, we propose a universal condition for thermal freeze-out of pions in heavy-ion collisions. We show that freeze-out occurs when the mean free path of pions lambda_f reaches a value of about 1 fm, which is much smaller than the spatial extent of the system at freeze-out. This critical mean free path is independent of the centrality of the collision and beam energy from AGS to RHIC.Comment: 5 pages, 3 figures, revised version resubmitted to PR