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The aim of the present study was to estimate the feasibility of blood serum hydrogen bonds energy distribution, and information-theoretic characteristics, as diagnostic markers for tumor disease in Graffi tumor bearing hamsters. Golden Syrian hamsters were randomly divided into two groups: a healthy control and an experimental one, challenged with Graffi tumor cells. The distributions of hydrogen bonds energies (-E) in the blood serum samples were investigated with a nonequilibrium process of droplets evaporation and sequential measurements of their wetting angle (Non-equilibrium Energy Spectrum (NES)). The measurements show significantly lower average hydrogen bond energy of the experimental samples than the controls. Shifts in NES toward depletion of (-E) at energy levels 0.0937, 0.1187, 0.1212, 0.1337, and 0.1387 eV, and an additional population at 0.0987, 0.1012, 0.1137, and 0.1237 eV energy levels were observed in the experimental samples compared to the controls. Such a pattern points to the possibility of utilizing the f(E) shifts at these energy levels as diagnostic markers of Graffi tumor in hamsters. Information-theoretic measures of Shannon entropy, Variation of information and Transformational information entropy were used to investigate possible differences between the experimental and control spectrum. Although they differ significantly in definitions, a comparison with the three information-theoretic measures did not reveal a statistically significant difference.

Innovative fibrous materials from cellulose derivative, cellulose acetate (CA) and water-soluble polyether, polyethylene glycol (PEG) loaded with natural biologically active compounds (BAC), quercetin (QUE) and rutin (RUT), have been successfully fabricated by blend electrospinning and dual electrospinning. Scanning electron microscopy revealed that the mean fiber diameters of all the obtained fibers were in the nanometer range. QUE and RUT incorporated in the fibrous mats were in the amorphous state, as evidenced by the performed differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The presence of the polyether in the developed fibrous material assisted the in vitro release of the biologically active compounds by improving the hydrophilicity and wettability of the mats. Rutin-containing fibrous materials manifest the highest antioxidative activity, as determined by the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method. The cytotoxicity of the fabricated novel materials was evaluated using a tumor cell line and normal mouse fibroblast cells. The mats containing QUE and QUE/RUT independent of the applied spinning method show a higher cytotoxic effect against cancer cells and 3 to 4.5 times lower cytotoxicity to a noncancer cell line. These features make the quercetin- and rutin-containing fibrous materials promising candidates for pharmaceutical, cosmetic, and biomedical use.

The Schiff base derivative (Ch-8Q) of chitosan (Ch) and 8-hydroxyquinoline-2-carboxaldehyde (8QCHO) was prepared and fibrous mats were obtained by the electrospinning of Ch-8Q/polylactide (PLA) blend solutions in trifluoroacetic acid (TFA). Complexes of the mats were prepared by immersing them in a solution of CuCl

The method of Non-equilibrium Energy Spectrum (NES) was applied in measurement of hydrogen bonds energy distribution in 1% Rosa damscena L. oil solution in deionized water. Local maxima in this spectrum were identical with these obtained in investigations of other biologically active solutions and related to particular bio effects as follows: (-0.1387 eV; 8.95 µm; 1117 cm-1). This local maximum is typical for antibacterial, anti-tumor and anti-inflammatory effects. The local maxima at (-0.1212 eV; 10.23 µm; 978 cm-1) and (-0.1262 eV; 9.82 µm; 1018 cm-1) are typical for anti-inflammatory effects and this at (-0.1112 eV; 11.15 µm; 897 cm-1) is typical for effects on the nervous system and nerve conductivity. Information theoretical analysis was performed using the values of Shannon entropy and Transformational information entropy, pointing to hydrogen bonds distribution similarities between Rosa damscena L., V. myrtillus L. and Salvia divinorum Epling. The possible chemical causes of these similarities were identified as antioxidant activity and polyphenols concentration.

During the past years, the synthesis of polymer prodrug structures, based on natural phytochemical compounds with a great range of valuable biological properties, has become a promising solution in cancer prevention, imaging, and detection. Curcumin (Curc) remains one of the most studied natural products, due to the impressive palette of biological properties and the possibility to be easily loaded in various micro- and nanostructures and chemically modified. In this study, pegylated curcumin derivatives were prepared by a direct esterification reaction between poly(ethylene glycol)diacid (PEG of 600 g/mol molar mass, PEG

The use of combination drug therapy instead of monotherapy is a new positive and promising approach in the treatment of cancer. Oxidal® and Pyrucet® are food supplements containing Methylene blue (USP), Caffeine (USP), Salicylic acid (USP) and Ethyl Acetoacetate and Ethyl Pyruvate respectively. The therapeutic significance of each of these compounds (their derivatives) is well established, but no data are available on their combined action in in vivo experimental tumor models. The aim of the present study was to investigate the in vivo protective effect of mono- and combined experimental therapy with dietary supplements Oxidal® and Pyrucet® in the Graffi myeloid tumor model in hamsters. For this purpose, the two drugs were administered alone or in combination in two treatment regimens - prophylactic (before) and therapeutic (simultaneously) with the transplantation of Graffi tumor cells. The protective effect was determined by the biometric parameters of tumor growth (transplantability, tumor size, mortality, mean survival time, survival rate) recorded during the experiment. The results showed a favorable effect of both drugs, administered alone or in combination, before and simultaneously with the transplantation of tumor cells on the appearance and development of Graffi tumor in hamsters. About 2-fold lower transplantability, prolongation of the latency period by 7 days, inhibition of tumor growth till 30thday of experiments, reduced mortality and increased individual and overall survival time between 7 to 10 days were observed in the Graffi tumor-bearing hamsters with experimental therapy compared to control-Graffi tumor-bearing hamsters, without therapy. The obtained data revealed that Oxidal® and Pyrucet® could be a promising candidate for the treatment of tumor diseases.

Hemocyanins (Hcs) are respiratory, oxygen-carrying metalloproteins that are freely dissolved in the hemolymph of many molluscs and arthropods. The interest in hemocyanins has grown significantly since it was found that they can be successfully used in immunotherapy of neoplastic diseases as non-specific or active stimulators of the immune system. The present study aims to assess the cytotoxicity, in vivo toxicity and antiproliferative activity of hemocyanins isolated from marine snail Rapana venosa (RvH), garden snails Helix lucorum (HlH) and Helix aspersa (HaH). For in vitro safety testing, 3T3 Neutral Red Uptake (NRU) test was used. The experiments for antiproliferative activity of the hemocyanins were performed by MTT assay on a panel of cell lines - a model of breast cancer. The in vivo toxicological assessment was performed by regular clinical examinations of hemocyanin-treated laboratory mice and histopathological analysis of hematoxylin/eosin stained preparations of parenchymal organs. The evaluation of the in vitro cytotoxicity showed that the tested hemocyanins does not induce toxic effects in nontumorigenic epithelial cell lines. In contrast, significant reduction of the viability of human breast carcinoma cell lines was found after treatment with high concentrations of hemocyanins. The in vivo experiments showed no signs of organ and systemic toxicity in the hemocyanin-treated animals. The presented data indicate that Hcs show a potential for development of novel anticancer therapeutics due to their beneficial properties, biosafety and lack of toxicity or side effects. Key words: hemocyanins (Hcs); cytotoxicity; antitumor activity; in vivo biosafety testing.

Diclofenac is one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for acute and chronic inflammatory conditions. Taking into consideration the extensive use of diclofenac, the crucial role of inflammation in tumorigenesis and data on the effects of NSAIDs on cancer cell lines, we investigated the cytotoxic potential of diclofenac on a panel of human cell lines originating from breast (MCF-7), cervical (HeLa) and colorectal cancer (HT-29). The cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye reduction assay and the half maximal inhibitory concentrations (IC50) were determined. Diclofenac had higher potency against MCF-7 and HT-29 than against HeLa. The cellular and nuclear changes were examined by fluorescent microscopy using 4′,6′-diamino-2-phenylindole (DAPI) stain and acridine orange/ethidium bromide (AO/EB). The wound-healing scratch assay showed significant reduction in the migration capacity of all tested cancer cell lines. The observed antineoplastic activity implies that the anticancer potential of NSAIDs and diclofenac, in particular, necessitates further investigation.

Electrospun membranes containing curcumin were prepared from poly(L-co-D,L-lactic) acid and polyvinylpyrrolidone. The effect of curcumin concentration on the solution viscosity and the morphology of fiber was studied. Curcumin solubility in aqueous solutions was enhanced by the formation of curcumin/polyvinylpyrrolidone water-soluble complex. Curcumin physico-chemical and therapeutic properties within the membranes were preserved upon UV-Vis light irradiation, as a part of the membranes sterilization. The biomaterials showed antibacterial activity against pathogenic microorganisms such as Staphylococcus aureus and Candida albicans. In-vitro experiments against HeLa and Graffi tumor cells and white blood cells (peritoneal macrophages and spleen lymphocytes) revealed potential biomedical application of the membranes. Electronic Supplementary Material (ESM) The online version of this article (doi: 10.1007/s12221-020-9473-z) contains supplementary material, which is available to authorized users.

Novel poly(vinyl alcohol) (PVA)/chitosan (Ch)-based fibrous materials containing an ionizable model drug, 8-hydroxyquinoline-5-sulfonic acid (SQ), were successfully fabricated by electrospinning. Complexes between the components of the crosslinked PVA/Ch/SQ mats and Cu2+ and Fe3+ ions were formed. The coordination of these ions in the mats was examined by electron paramagnetic resonance spectroscopy (EPR). The microbiological screening against S. aureus and C. albicans revealed that both the incorporation of SQ in the mats and the complexation with Cu2+ and Fe3+ imparted to these materials antibacterial and antifungal activities. Moreover, the SQ-containing mats and their complexes displayed good cytotoxicity against human cervical HeLa tumor cells. The most prominent was the cytotoxicity of the Cu2+ complex of the mats. The combined antibacterial, antifungal and in vitro antitumor activities render these novel materials promising candidates for wound dressing applications and for application in the local treatment of cervical tumors.

Novel eco-friendly fibrous materials with complex activities from cellulose acetate and cellulose acetate/polyethylene glycol (CA,PEG) containing 5-chloro-8-hydroxyquinoline as a model drug were obtained by electrospinning. Several methods, including scanning electron microscopy, X-ray diffraction analysis, ultraviolet-visible spectroscopy, water contact angle measurements, and mechanical tests, were utilized to characterize the obtained materials. The incorporation of PEG into the fibers facilitated the drug release. The amounts of the released drug from CA/5-Cl8Q and CA,PEG/5-Cl8Q were 78 ± 3.38% and 86 ± 3.02%, respectively (for 175 min). The antibacterial and antifungal activities of the obtained materials were studied. The measured zones of inhibition of CA/5-Cl8Q and CA,PEG/5-Cl8Q mats were 4.0 ± 0.18 and 4.5 ± 0.2 cm against S. aureus and around 4.0 ± 0.15 and 4.1 ± 0.22 cm against E. coli, respectively. The complete inhibition of the C. albicans growth was detected. The cytotoxicity of the obtained mats was tested toward HeLa cancer cells, SH-4 melanoma skin cells, and mouse BALB/c 3T3 fibroblasts as well. The CA/5-Cl8Q and CA,PEG/5-Cl8Q materials exhibited anticancer activity and low normal cell toxicity. Thus, the obtained fibrous materials can be suitable candidates for wound dressing applications and for application in local cancer treatment.

Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of arthropods and mollusks that attract scientific interest with their diverse biological activities and potential applications in pharmacy and medicine. The aim of the present study was to assess the in vitro antitumor activity of hemocyanins isolated from marine snail Rapana venosa (RvH) and garden snails Helix lucorum (HlH) and Helix aspersa (HaH), as well the mucus of H. aspersa snails, in the HT-29 human colorectal carcinoma cell line. The effects of the hemocyanins on the cell viability and proliferation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alterations in the tumor cell morphology were examined by fluorescent and transmission electron microscopy. The results of the MTT assay showed that the mucus and &alpha, subunit of hemocyanin from the snail H. aspersa had the most significant antiproliferative activity of the tested samples. Cytomorphological analysis revealed that the observed antitumor effects were associated with induction of apoptosis in the tumor cells. The presented data indicate that hemocyanins and mucus from H. aspersa have an antineoplastic activity and potential for development of novel therapeutics for treatment of colorectal carcinoma.

Myosmine, 3-(1-pyrroline-2-yl) pyridine is a minor tobacco alkaloid that has also been found in various widely used foods. Recently, this phytochemical has been gaining an increasing interest as a potential risk factor for the development of oesophageal adenocarcinoma. This study aimed to examine the effects of myosmine on the cell viability and proliferative activity of erythroleukemia and hepatocellular carcinoma cells and to obtain additional information about the mechanisms underlying its cytotoxic activity. The in vitro cytotoxic effect of myosmine on the HepG2 and MEL tumour cell lines was assessed by MTT dye reduction and trypan blue dye exclusion assays. The alterations in the tumour cell morphology induced by myosmine were analysed by fluorescent microscopy after staining with acridine orange (AO)/ethidium bromide (EtBr) and 4′,6-diamidine-2′-phenylindole dihydrochloride (DAPI). Annexin V-FITC/propidium iodide (PI) staining was used to assess the apoptosis-inducing ability of myosmine. The modulating action of antioxidant treatment on myosmine-induced cytotoxicity against the HepG2 tumour cell line was also examined. The cell viability tests indicated that myosmine induced a significant dose-dependent reduction of the viability and proliferative activity of both tumour cell lines. Fluorescent microscopy studies revealed marked alterations in the morphology of myosmine-treated tumour cells with signs of cell cycle arrest and apoptosis. The results of the simultaneous treatment with myosmine and vitamin C showed modulating activity of vitamin C on the cytotoxic effect of myosmine with concentration- and time-dependent variations. The presented results could contribute to the assessment of the potential health risks associated with the dietary myosmine exposure. Abbreviations AO: acridine orange; DAPI: 4‘,6-diamidine-2‘-phenylindole dihydrochloride; DMEM: Dulbecco's modified Eagle medium; DMSO: dimethyl sulfoxide; EtBr: ethidium bromide; FITC: fluorescein isothiocyanate; GERD: gastroesophageal reflux disease; MEL: murine erythroleukemia; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NNN: N'-nitrosonornicotine; PBS: phosphate buffered saline; PI: propidium iodide

Herein we pay attention to the design, synthesis and sensor activity of a novel biocompatible perylene-3,4,9,10-tetracarboxylic diimide (PDI) pH-probe in water. The synthesized compound shows selective fluorescence signalling properties as a function of pH (pKa value of 6.35 ± 0.02) which makes the probe suitable for pH determination in the physiological range. Thus prepared water soluble fluorescent system demonstrate low cytotoxicity to L929 cell lines from 330 μM to 1.3 μM and cell permeability in the lower concentration range. That findings show the high potential of the newly prepared PDI probe for monitoring of pH variations in bio-samples.

Composite fibrous materials are prepared from poly(ethylene oxide) (PEO) and beeswax (BW) by single-spinneret electrospinning using chloroform as a common solvent. The obtained fibers have core-sheath-like structure, as evidenced by the water contact angle values and corroborated by the results on the elemental composition of the fiber's surface determined by X-ray photoelectron spectroscopy (XPS) and by analyses with scanning electron microscopy of fibers before and after selective extraction of PEO or BW. Furthermore, the core-sheath-like structure is proven by transmission electron microscopy. This is attributed to self-assembly of BW molecules on the surface of the formed fibers driven by the incompatibility between PEO and BW. 5-Nitro-8-hydroxyquinoline (NQ) is embedded as a model drug with antibacterial, antifungal, and anticancer properties in the PEO/BW fibrous materials. XPS analyses reveal that NQ is present on the surface of the PEO/BW/NQ materials. Using a purposely designed cell for fixation of the fibrous materials the NQ release in phosphate buffer solution with рН 7.4 is followed. The new PEO/BW/NQ fibrous materials exhibit antibacterial activity against S. aureus and E. coli, antifungal effect against C. albicans, and selective anticancer activity against HeLa (human cervical adenocarcinoma cells) and SH-4 (human melanoma cells) cell lines.

Novel fibrous materials from poly(ε-caprolactone) (PCL), chitosan (Ch) and natural phenolic acid ferulic acid (FA) of diverse design were successfully prepared by electrospinning or electrospinning combined with dip-coating. FA incorporated in the PCL fibrous mats or in the Ch coating was in the amorphous state as evidenced by the performed differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The release of FA was affected by the composition and design of the polymer matrix. The incorporation of a combination of FA and Ch in the fibrous mats imparted to these materials higher killing rates against pathogenic bacteria S. aureus than that of FA-containing mats or Ch-coated mats alone. The FA-containing fibrous materials as well as those coated with Ch or Ch-FA inhibited the adhesion of S. aureus bacteria. Moreover, FA preserved its antioxidant activity when incorporated in the fibers or in the Ch coating. It was found that the cytotoxicity of all types of FA-containing mats against HeLa tumor cells was higher than that of the free FA. Thus, the obtained fibrous materials can be suitable candidates for wound dressing applications and for application in local treatment of cervical tumors.

Novel fibrous materials from polylactide (PLA) and Schiff base from Jeffamine ED® and 8-hydroxyquinoline-2-carboxaldehyde (Jeff-8Q) or its complex with Cu

The aim of present study was to obtain novel fibrous materials based on cellulose derivative and polyethylene glycol loaded with natural biologically active compound quercetin by electrospinning. Several methods including scanning electron microscopy (SEM), IR spectroscopy, X-ray diffraction analysis (XRD), water contact angle measurements, differential scanning calorimetry (DSC), and UV-VIS spectroscopy were utilized to characterize the obtained materials. The incorporation of polyethylene glycol in the fibrous material resulted in increased hydrophilicity and burst release of quercetin from the fibers. Quercetin-containing fibrous mats exhibited high antioxidant activity as estimated by DPPH free radical scavenging method. In vitro tests with HeLa tumor cells and SH-4 melanoma skin cells were performed in order to determine the cytotoxicity of the novel materials. It was found that the fibrous CA/PEG/QUE materials exhibited high cytotoxic effect against both cell lines. Therefore, the novel polymeric materials containing quercetin are promising candidates for biomedical and pharmaceutical applications.

Novel fibrous materials from polylactide (PLA) and Schiff base from Jeffamine ED® and 8-hydroxyquinoline-2-carboxaldehyde (Jeff-8Q) or its complex with Cu2+ (Jeff-8Q.Cu2+) were successfully prepared by using one-pot electrospinning or electrospinning combined with dip-coating. These approaches enabled the fabrication of materials of diverse design: non-woven textile in which Jeff-8Q or Jeff-8Q.Cu2+ was predominantly in the fibers' bulk (type “in”) or was deposited as a thin film on the surface of the fibers (type “on”). The morphology of the mats and chemical composition of their surface were analyzed by means of scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The coordination of Cu2+ ions in Jeff-8Q.Cu2+/inPLA and Jeff-8Q.Cu2+/onPLA mats was examined by electron paramagnetic resonance (EPR) spectroscopy. It was found that the in vitro release of Jeff-8Q (Jeff-8Q.Cu2+) from the type “on” mats was more rapid than that of the type “in” mats. Enhancement of the antioxidant activity of the Jeff-8Q.Cu2+-containing fibrous mats as compared to mats containing Jeff-8Q was observed. In contrast to the neat PLA mat, the Jeff-8Q- and Jeff-8Q.Cu2+-containing mats (both type “in” and “on”) displayed high in vitro antitumor activity against human cervical HeLa cells. The obtained materials are promising for use in local tumor treatment.

Antiproliferative effects of biochemically isolated from Trichinella spiralis muscle larvae, livers and spleens from healthy and T. spiralis infected rats heat-sensitive bioactive substances (HSBSes) were studied in vitro on nonactivated and mitogen activated with phytohemagglutinin (PHA) lymphocytes and bone marrow precursor cells. Stronger antiproliferative effects were established for HSBSes from parasite and infected host tissues than from healthy rats. Stronger growth inhibiting and immune modulating activ-ities of HSBSes were determined on PHA activated lymphocytes. Also antiproliferative effects were established on bone marrow precursor cells. This probably was a result of changed liver metabolism and immunity in T. spiralis infected hosts., {"references":["Aranzamendi, C., F. Fransen, M. Langelaar, F. Franssen, P. Van Der Ley, J. Van Putten, V. Rutten, E. Pinelli. (2012). Trichinella spiralis-secreted products modulate DC functionality and expand regulatory T cells in vitro. Parasite Immunology, 34, 210–223.","Balazh, A. & I. Blazhek. (1982). Control of cell proliferation by endogenous inhibitors. Mir Publishing House, Moscow, pp. 302, (In Russian).","Bliss, S. K., S. P. Bliss, D. P. Beiting, A. Alcaraz, J. A. Appleton. (2007). IL-10 regulates movement of intestinally derived CD4+ T cells to the liver. The Journal of Immunology, 178, 7974–7983.","Duan, L. X., X. M. Guan, C. S. Zhang, P. Ru, J. Ni, Y. M. Su, L. F. Chen, X. C. Zhang. (2011). Research progress on anti-tumor mechanism of Trichinella spiralis. Chinese Journal of Parasitology and Parasitic Diseases, 29, 2, 142–146. (In Chinese).","Gong, P., J. Zhang, L. Cao, Z. Nan, J. Li, Yang J, H. Fang, H. Jiao, T. Jiang, L. Su, X. Zhang. (2011). Identification and characterization of myeloma-associated antigens in Trichinella spiralis. Exp. Parasitol., 127, 4, 784–788.","Gruden-Movsesijan, A. & L. Sofronic-Milosavjevic. (2010). Experimental trichinellosis in rats – peritoneal macrophage activity. Arch. Biol. Sci., Belgrade, 62, 1, 15–22.","Guo, K., X. Sun, Y. Gu, Z. Wang, J. Huang, X. Zhu. (2016). Trichinella spiralis paramyosin activates mouse bone marrow-derived dendritic cells and induces regulatory T cells. Parasites & Vectors, 9, 569.","Ilic, N., M. Colic, A. Gruden-Movsesijan, I. Majstorovic, S.Vasilev, L. Sofronic-Milosavljevic. (2008). Characterization of rat bone marrow dendritic cells initially primed by Trichinella spiralis antigens. Parasite Immunology, 30, 9, 491–495","Ivanov, D., R. Milcheva, S. Petkova, M. Gabrashanska. (2014). Serum sialic acid levels in Trichinella spiralis infected rats. Comptes rendus de l'Academie bulgare des Sciences, 2014, 2, 217–222.","Petkova, S., E. Gabev, L. Mihov, M. Bogoeva, E. Pozio, N. Astrukova. (2005). Therapeutic activity of mebendazole on murine experimental model on the muscle stage of trichinellosis. Comptes rendus de l'Academie bulgare des Sciences, 58, 1, 97–102.","Sofronic-Milosavljevic, L, N. Ilic, E. Pinelli, A. Gruden-Movsesijan. (2015). Review Article. Secretory products of Trichinella spiralis muscle larvae and immunomodulation: Implication for autoimmune diseases, allergies and malignancies. Hindawi Publishing Corporation, Journal of Immunology Research, Article ID 523875, http://dx.doi.org/10.1155/2015/523875.","Tsocheva-Gaytandzhieva, N. T. (2005). Review Article: Fasciolosis and tumour growth. Helminthologia (Bratislava), 42, 2, 107–113.","Tsocheva-Gaytandzhieva, N. T. (2006). Chronic fasciolosis and endogenous inhibitors of cell proliferation. Professor Marin Drinov Academic Publishing House, Bulgarian Academy of Science, Sofia, Bulgaria, First Edition, pp. 108 (In Bulgarian).","Tsocheva-Gaytandzhieva, N. T. (2016). Effects of nematode infections on tumors in animals and on tumor cell cultures. Proceedings of the Seventh Workshop of Experimental Models and Methods in Biomedical Research, May 16–18, 2016, Sofia, Bulgaria.","Tsocheva-Gaytandzhieva, N., R. Toshkova, E. Gardeva, L. Yossifova, S. Petkova, V. Nanev. (2016). Antiproliferative activity against tumour cells of biologically active substances isolated from livers of healthy and Trichinella spiralis infected rats. Comptes rendus de l'Academie bulgare des Sciences, 69, 11, 1443–1448.","Verly, W. G., Y. Deschamps, J. Pushpathadam. (1971). The hepatic chalone. I. Assay method for the hormone and purification of the rabbit liver chalone. Canadian J. Biochem., 49, 1376–1383.","Wang, X. L., B. Q. Fu, S. J. Yang, X. P. Wu, G. Z. Cui, M. F. Liu, Y. Zhao, Y. L. Yu, X. Y. Liu, H. K. Deng, Q. J. Chen, M. Y. Liu. (2009). Trichinella spiralis – a potential anti-tumor agent. Veterinary Parasitology, 159, 249–252."]}

Berberine chloride (Brb) is a natural isoquinoline quaternary alkaloid that displayed a set of beneficial biological properties such as antioxidant, antimicrobial, antitumor, anti-inflammatory, and antiviral. Brb is poorly soluble in water and body fluids and its intestinal absorption is very low, which predetermine its low bioavailability. Polymeric nanoparticles seem to be a good platform to overcome these drawbacks. In this study, for the first time, stable aqueous dispersions of nanoparticles (NPs) based on complexes of Brb and poly(methacrylic acid) (PMA) or poly(acrylic acid) (PAA), were successfully prepared by mixing their dilute aqueous solutions as evidenced by the performed dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. It was found that the mean diameter and zeta potential of NPs depended on the Brb molar fraction. In the case of Brb/PMA and Brb/PAA NPs the encapsulation efficiency was observed to approach a maximum value of 58.9 ± 0.5% and of 78.4 ± 0.9%, respectively, at values of Brb molar fraction at which maximum amount of complexes was obtained. The performed differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses revealed that Brb incorporated in the NPs was in the amorphous state. The Brb release profile was pH-dependent. The Brb-containing NPs displayed good antioxidant capacity close to that of free Brb. In vitro cell viability studies demonstrated that the Brb/PMA (PAA) NPs exerted a higher cytotoxicity against HeLa tumor cell than non-tumor BALB/c 3T3 mouse fibroblast cells. Thus, the obtained NPs are promising candidates in the drug delivery systems in the treatment of cervical tumors.

Curcumin (Curc) exhibits anti-inflammatory, antibacterial and antitumor activity. However, its clinical application is limited by its poor bioavailability related to its extremely low water solubility. Novel materials allowing enhanced release of Curc in aqueous medium were obtained. The new materials consisted of electrospun fibers from cellulose acetate (CA) (mean fiber diameter ca. 780 nm ± 110 nm) with electrosprayed Curc/polyvinylpyrrolidone (Curc/PVP) particles. Scanning electron microscopy (SEM) showed that separated and evenly distributed particles of Curc/PVP were deposited on the surface of the mats and on the inner layers of the mat. X-ray diffraction studies showed that Curc was in amorphous state. In vitro studies demonstrated that Curc release was facilitated from Curc/PVP-on-CA mats (ca. 78% for 24 h) compared with the materials in which Curc was incorporated in CA fibers (17% for 24 h). Moreover, the curcumin-containing materials exhibited antibacterial activity against Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). Curc/PVP-on-CA fibrous mats exhibited high in vitro cytotoxicity towards HeLa tumor cells. Therefore, the obtained materials are promising for antibacterial wound dressing applications as well as for application in local treatment of cervical tumors.

Pure C-phycocyanin (C-PC) was isolated from Arthronema africanum to evaluate its potential antitumor effects in vivo and in vitro. Experimental myeloid Graffi tumor in hamsters was used as a model. The cell proliferation assay showed that C-PC treatment, at concentration of 100 µg mL -1 for 24 h, significantly inhibited the growth of Graffi tumor cells (51.4% viability). Agarose gel electrophoresis of the genomic DNA of treated cells displayed time- and concentration-dependent fragmentation pattern, typical for apoptosis. Apoptotic process was related to the increase in cellular manganese and copper/zinc superoxide dismutases and glutathione reductase activities, coupled with a low catalase activity. In vivo C-PC administration (5.0 mg kg -1 body weight) suppressed the tumor transplantability and growth, while the mean survival time of the tumor-bearing hamsters was increased. The results revealed promising antitumor activities of A. africanum C-PC and suggested the potential of this natural biliprotein pigment for future pharmacological and medical applications. The study provided new data on the mechanism of the C-PC-induced apoptosis in which the imbalance of antioxidant enzymes that favoured hydrogen peroxide accumulation might play a leading role. Key words: Antitumor activity, Arthronema africanum , In vivo , In vitro , C-pycocyanin, Myeloid Graffi tumor

The optical properties of gold nanoparticle clusters are presented from the point of view of their applications in biophotonics, where the absorption and scattering spectra are crucial. Generalised multiparticle Mie theory and finite difference time domain (FDTD) technique are used for theoretical description of the far- and nearfield optical properties of two dimensional nanoparticle ensembles. The system under consideration consists of spherical gold nanoparticles from 20 to 200 nm in diameter, forming 2D clusters in water. The properties of the far-field absorption and scattering spectra as a function of the cluster size, particle dimensions, and interparticle distance are investigated for ordered hexagonal structure of the particle arrays. It is found that the absorption efficiency can be shifted to the IR spectral range by increasing array size and decreasing interparticle distance. The increase in the array size also results in enhancement of the scattering efficiency while the absorption is reduced. The near-field intensity distribution is inhomogeneous over the array, as formation of zones with intensity enhancement of about two orders of magnitude is observed in specific areas. The optical properties of an ensemble whose configuration is reproduced from real experiments of gold nanoparticle deposition onto cancer cells are also presented. The results obtained can be used in designing of nanoparticle arrays with applications in biophotonics, bioimaging and photothermal therapy.

Rabbits and rats were inoculated with material derived from FLK cells producing permanently bovine leukaemia virus (BLV). The viral presence in the inoculum was proved by transmission electron microscopy, immunofluorescence, immunogold labelling demonstrating viral Tax protein, and PCR analysis. About 30 % of the infected animals sustained BLV seropositivity during the experiment, and demonstrated symptoms of lympholeukaemia - clinical manifestation of an immunosuppressive condition, increased number of lymphocytes and lymphoblasts, and preneoplastic lymphoid cell accumulations in the liver, lungs, kidneys, and lymph nodes. BLV DNA, detected by PCR in diseased animals, indicates the role of BLV as an aetiological factor of lympholeukaemia, developed in these animals after BLV infection. The alterations in rats were more pronounced than those in rabbits. The results prove that these two species of laboratory animals, especially rats, are suitable models for the in vivo studies of leukaemogenesis caused by BLV/HTLV infections.

The cytotoxic, antibacterial, and antifungal activities of cyanobacterium Gloeocapsa sp. strain Gacheva 2007/R-06/1 were investigated and the possibility for an enhancement of these activities by changing the culture conditions evaluated. Fatty acids of this cyanobacterium were found to be active against Streptococcus pyogenes. Exopolysaccharides inhibited the growth of both Gram-positive and Gram-negative bacteria and the fungus Candida albicans. Both exopolysaccharides and fatty acid mixtures also significantly decreased the viability of human cervical carcinoma cells, HeLa. Greater biological activities were exhibited by Gloeocapsa sp., cultured at suboptimal temperatures (15–26°C) than at optimal and supraoptimal ones. In comparison with higher light intensity, the low-light cultivation stimulated the cytotoxicity of the fatty acids. In general, low temperatures decreased the growth of Gloeocapsa sp., but promoted its biological activity. Prolonged cultivation also had a beneficial impact on the bioactivity. Compared to 4 days, the 17-day cultivation resulted in fourfold higher antibacterial and antifungal activities of exopolysaccharides and more than twice increases in their cytotoxicity. The study revealed that this cyanobacterial isolate is a new source of natural products with potential for pharmacological and medical applications.

The efforts of scientists are aimed at finding anti-cancer agents of natural origin which have high biological activity, low toxicity and broad spectrum of therapeutic activity. This study was desi...

The antiproliferative activity of electrospun mats of poly(L-lactide- co-D,L-lactide) (coPLA) containing quaternized chitosan (QCh) and/or doxorubicin hydrochloride (DOX) was evaluated against the Michigan Cancer Foundation-7(MCF-7) human breast carcinoma cell line. QCh- and DOX-containing nanofibrous mats possess good antiproliferative activity and decrease considerably the viability of the MCF-7 cells for the different periods of cell incubation as confirmed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Fluorescent microscopy analyses and scanning electron microscopy observations revealed that apoptosis was one of the major mechanisms of MCF-7 cell death induced by the QCh- and DOX-containing mats.

Theoretical and experimental results on the heating process of gold nanoparticles irradiated by nanosecond laser pulses are presented. The efficiency of particle heating is demonstrated by in-vitro photothermal therapy of human tumor cells. Gold nanoparticles with diameters of 40 and 100 nm are added as colloid in the cell culture and the samples are irradiated by nanosecond pulses at wavelength of 532 nm delivered by Nd:YAG laser system. The results indicate clear cytotoxic effect of application of nanoparticle as more efficient is the case of using particles with diameter of 100 nm. The theoretical analysis of the heating process of nanoparticle interacting with laser radiation is based on the Mie scattering theory, which is used for calculation of the particle absorption coefficient, and two-dimensional heat diffusion model, which describes the particle and the surrounding medium temperature evolution. Using this model the dependence of the achieved maximal temperature in the particles on the applied laser fluence and time evolution of the particle temperature is obtained.

Nanofibrous materials containing the antitumor drug doxorubicin hydrochloride (DOX) were easily prepared using a one-step method by electrospinning of DOX/poly(L-lactide-co-D,L-lactide) (coPLA) and DOX/quaternized chitosan (QCh)/coPLA solutions. The pristine and DOX-containing mats were characterized by ATR-FTIR and X-ray photoelectron spectroscopy (XPS). The release rate of DOX from the prepared fibers increased with the increase in DOX content. The DOX release process was diffusion-controlled. MTT cell viability studies revealed that incorporation of DOX and QCh in the nanofibrous mats led to a significant reduction in the HeLa cells viability. It was found, that the antitumor efficacy of the DOX-containing mats at 6 h was higher than that of the free DOX. SEM, TEM, and fluorescence microscopic observations confirmed that the antitumor effect of QCh-based and DOX-containing fibrous mats was mainly due to induction of apoptosis in the HeLa cells.

Synthesis and impact on the tumour growth of palladium(II) complex of 5-amino-1,10-phenanthroline Pd(5-NH 2 -phen) 2 (NO 3 ) 2 and the protonated dimer (phen) 2 (H + )(BF 4 − ) have been described. In the reported experiments a cancerous (100% lethality) myeloid subcutaneous tumour (with Graffi-tumour origin) in hamsters was used. The animals were injected i.p. with different doses of the substances. The longest mean survival time (1.65 times longer than the controls) was achieved when the substance Pd(5-NH 2 -phen) 2 (NO 3 ) 2 was injected into the animals. One of the animals even survived until the 71st day, which is 2.2 times longer than the controls. The compound (phen) 2 (H + )(BF 4 − ) prolonged the mean life-time of the animals 1.4 times in comparison to the controls. On the other hand, the Pd(II) complex of 1,10-phenanthroline, Pd(phen) 2 (H 2 O)(NO 3 ) 2 , did not reveal any antitumour activity. Our experience concerning the effect of other drugs on this tumour has shown a survival time no longer than 4–5 d after the death of the controls.

The cell wall sulfated polysaccharide of the red microalga Porphyridium cruentum (Rhodophyta) (PcrPSH) exhibited strong antitumor activity against Graffi myeloid tumor in hamsters both in vitro and...

The purpose of this work was to investigate the possibility for the preparation of new poly(3-hydroxybutyrate) (PHB)/poly(ethylene glycol) (PEG)-based fibrous materials containing natural phenolic compound caffeic acid (CA) of diverse architectures, as well as to study the impact of the fiber composition on the in vitro CA release profile and on the biological properties of the fibrous materials. The application of the one-pot electrospinning enabled the fabrication of nanofibrous materials from PHB and PEG loaded with the CA. Materials with targeted design were obtained by coating with polyelectrolyte complex of alginate (Alg) and N,N,N-trimethylchitosan (TMCh). Three different processing paths were used to obtain coated mats: (i) with CA incorporated in the PHB/PEG core; (ii) with CA embedded in the Alg layer; and (iii) with CA included in the TMCh layer. The in vitro release of CA was modulated by controlling the composition and the architecture of the nanofibrous mats. The performed microbiological screening and MTT cell viability studies revealed that in contrast to the bare mats, the CA-containing nanofibrous materials were effective in suppressing the growth of the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli and displayed good cytotoxicity against human cervical HeLa tumor cells. In addition, the proliferation of murine spleen lymphocytes and peritoneal macrophages was increased by the prepared CA-containing nanofibrous materials. The obtained materials are promising for antibacterial wound dressing applications as well as for application in local treatment of cervical tumors.

Influenza infection was induced in white mice by intranasal inoculation of the virus A/Aichi/2/68 (H3N2). The lung protease and the protease-inhibitory activities were followed for 9 days after infection. The intranasal application of a polyphenol-rich extract (PC) isolated from Geranium sanguineum L. induced a continuous rise in the anti-protease activity but did not cause substantial changes in the lung protease activity of healthy mice. Influenza virus infection triggered a slight reduction in protease activity in the lungs at 5 and 48 h post infection (p.i.) and a marked increase at 24 h and 6 day p.i. Protease inhibition in the lungs was reduced at 24 and 48 h p.i. and an increase was observed at 5 h and 6 and 9 days p.i. PC treatment brought both activities to normal levels. The restoration of the examined parameters was consistent with a prolongation of mean survival time and reduction of mortality rate, infectious virus titre and lung consolidation. PC reinstated superoxide production by alveolar macrophages and increased their number in virus-infected mice. The favourable effect on the protease and the protease-inhibitory activities in the lungs of influenza-virus-infected mice apparently contributes to the overall protective effect of PC in the murine experimental influenza A/Aichi infection. The antiviral effect of the individual constituents was evaluated.