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  This is an Open Access Journal Open Access journal
ISSN (Online) 2050-2966
Published by Pensoft Homepage  [21 journals]
  • Antibacterial activity of thin films TiO2 doped with Ag and Cu on
           Gracilicutes and Firmicutes bacteria

    • Abstract: BioDiscovery 20: e21596
      DOI : 10.3897/biodiscovery.20.e21596
      Authors : Dragomira Stoyanova, Iliana Ivanova, Orlin Angelov, Todorka Vladkova : This article aims to explore the antibacterial activity of thin films of TiO2 doped with Ag and Cu using two types of Gram-negative and Gram-positive test bacteria with clinical significance (Gracilicutes and Firmcutes bacteria). The thin films (thickness of about 60 nm) were deposited on glass substrates by radio frequency magnetron co-sputtering (r.f. power of 50 W) of TiO2 target with Ag and Cu pieces on its surface in an Ar atmosphere (0.8 Pa) without heating during the deposition. The total surface area of the Ag was 60 mm2 and that of the Cu was 100 mm2. Bacillus cereus, Staphylococcus epidermidis, Salmonella enterica, Escherichia coli and Pseudomonas sp. were used as test strains. The antibacterial actvity of the films was evaluated by the classical Koch's method and optical density measurements. The bactericidal effect was established at different time points between 30 min and 90 min for Pseudomonas sp. and S. enterica. The Firmicutes bacteria B. cereus and S. epidermidis were killed at the 4th and 8th hour of the treatment, respectively. The effect on E. coli was bacteriostatic until the 10th hour. The results were confirmed by assessment of the bacterial dehydrogenase activity. The studied thin films of TiO2 co-doped with Ag and Cu have a potential for application as antibacterial coatings. HTML XML PDF
      PubDate: Fri, 15 Dec 2017 15:27:23 +020
  • Identification of the gene complexes that determine some individual
           characteristics of a person

    • Abstract: BioDiscovery 20: e21998
      DOI : 10.3897/biodiscovery.20.e21998
      Authors : Irma Mosse, Alexander Kilchevsky, Alexander Gonchar, Maxim Ameliyanovich, Nikita Sedlyar : There are some data about genes associated with certain traits of a person in the scientific literature, but these data are often contradictory. It is evident that complexes of genes that affect the manifestation of the trait can be more informative. We have investigated genotypes of 9000 people, using the PCR method, in order to determine their athletic abilities or predisposition to different diseases and pathologies. In particular, we tested about 3000 women with unknown causes of miscarriages for 14 genes associated with the pregnancy development. 1,5 years later we interviewed 700 women and have identified a high genetic risk of pregnancy loss due to hereditary thrombophilia. In most of the cases, doctors took into account our data and applied for these women treatment with anticoagulant drugs such as fragmin in the subsequent pregnancies. So 86.6% of pregnant women have successfully conceived and given birth, and we have received over 500 touching letters of gratitude. Thus, genetic testing allows to identify individual human properties in order to prevent some pathologies or to chose the most suitable kind of sport. HTML XML PDF
      PubDate: Mon, 6 Nov 2017 15:36:24 +0200
  • Innovative sterilization technology - bacterial inactivation by cold argon

    • Abstract: BioDiscovery 20: e21977
      DOI : 10.3897/biodiscovery.20.e21977
      Authors : Yovana Todorova, Ivaylo Yotinov, Yana Topalova, Plamena Marinova, Evgenia Benova, Mariana Atanasova, Todor Bogdanov : Non-thermal (cold) plasma is subject of intensive scientific interest as an alternative sterilization technique for advanced control of microbial quality and safety in food biotechnology. The cold plasma is a flow of weakly ionized gas at atmospheric pressure that includes radicals, H2O2, O3, ultraviolet radiation, charged particles, exited metastable atoms, electric fields. One of the major benefits of plasma-based technologies is the synergy between the strong effects of these highly active components that provides a high bactericidal efficiency at low costs, time-saving and non-toxicity. The aim of this study is to assess the bactericidal effect of cold argon plasma in liquids and surfaces, contaminated with Gram-negative and Gram-positive spore-forming bacteria. The used plasma source is surface-wave-sustained discharge (SWD) operating at 2.45 GHz in argon (plasma torch) produced by an electromagnetic wave launcher surfatron type. The bactericidal effect was studied by direct contact treatment of contaminated liquids and agar plates with Pseudomonas aureofaciens AP-9 and Brevibacillus laterosporus BT-271. The results show that the cold argon plasma is able to inactivate bacteria at short exposure time (under 1 min). The clear sterilization zones on treated surfaces with diameter depending on exposure time and initial bacterial density were obtained. In bacteria-contaminated liquids the partial disinfection was observed at least. The potential of plasma based technologies as innovative sterilization approach is high and can be used for various purposes related to microbial control and food safety. HTML XML PDF
      PubDate: Fri, 3 Nov 2017 20:47:28 +0200
  • Participation of NO-synthase in Control of Nitric Oxide Level in Rat
           Hippocampus after Modelling of Ischaemic and Haemorrhagic Insult

    • Abstract: BioDiscovery 20: e14810
      DOI : 10.3897/biodiscovery.20.e14810
      Authors : Khalil L. Gainutdinov, Svetlana G. Pashkevich, Vyatcheslav V. Andrianov, Guzel G. Yafarova, Margarita O. Dosina, Tatiana Kh. Bogodvid, Julia P. Stukach, Dinara I. Silant'eva, Aleksandra S. Zamaro , Timur V. Sushko, Vladimir Kulchitsky : Electron paramagnetic resonance (EPR) was used as a method for recording the content of the nitric oxide (NO) in hippocampal tissues of intact rats and rats after modelling of ischaemic and haemorrhagic stroke. Based on direct measurements of NO by EPR spectroscopy, it was shown that, within 5 hours after the onset of symptoms of ischaemic and haemorrhagic stroke, the formation of NO in the hippocampus was reduced by a factor of 2-3 and this reduction was maintained for a period of between 24 and 72 hours. The results show that a systemic character of a decrease in the intensity of NO production during the modelling of ischaemic events in the brain reflects the effects of central dysregulation of the functions at the level of the whole organism such that it is appropriate to consider implementing the correction of the vital systems of the body in a stroke. It has indicated that non-selective NO-synthase blocker L-NAME reduced the low level of NO production by a factor of 3 by its administration within 72 hours after post-ischaemic and haemorrhagic stroke. It was discovered however that L-NAME returns the level of NO production to baseline (control) by its administration within 5 hours after ischaemia. HTML XML PDF
      PubDate: Wed, 18 Oct 2017 12:05:23 +030
  • Pilot assessment of cyanotoxins as potential risk factors for cancer in

    • Abstract: BioDiscovery 20: e20501
      DOI : 10.3897/biodiscovery.20.e20501
      Authors : Maya Stoyneva-Gärtner, Blagoy Uzunov, Petya Dimitrova : Cyanoprokaryotes (=cyanobacteria, blue-green algae) are the most ancient oxygen-producing phototrophic microorganisms, spread all over the Globe, which form the important basis of different food chains in aquatic and terrestrial habitats. However, due to strong anthropogenic pressure during the last decades they are also responsible for causing nuisance algal blooms in different water bodies with deleterious effects on the mankind and ecosystems mainly due to production of toxic substances (cyanotoxins). Amongst them are the microcystins, nodularins, lyngbyatoxins and aplysiatoxins, known as tumor-promotors with increase of exposure routes through which humans and animals can be placed at risk (Meriluoto et al. 2017). However, the investigations on the relations between the occurrence and development of such diseases with the cyanotoxins and their producers are extremely scarce at a global scale (Yu and Chen 1994, Ueno et al. 1996, Fleming et al. 2002, Svircev et al. 2009, Drobac et al. 2011, Labine et al. 2015). During the last 15 years cyanoblooms and microcystins, nodularins and saxitoxins were detected in 16 different Bulgarian freshwater bodies, including some drinking-water reservoirs (Stoyneva-Gärtner et al. 2017). Amongst the detected toxins some new forms were recognized by their characteristic spectra (Pavlova 2007, Pavlova et al. 2007), and, more recently, a new potential producer of lyngbyatoxin was found in the Black Sea (Stoyneva et al. 2015). The poster shows a pilot assessment of the spread of cancer distribution and mortality vs. spread of cyanoblooms and cyanotoxins in Bulgaria. The pilot assessment is made on the basis of comparison of the general regions of spread of cyanotoxins in Bulgarian water bodies and toxin-producing cyanospecies during the period 2000-2017 (Stoyneva-Gärtner et al. 2017) with the spread of cancer in Bulgaria (e.g. Valerianova et al. 2015). The comparison shows general conformities between the spread of the “most dangerous” water bodies and main regions of cancer diseases in the country. The results obtained served as a basis for a new project proposal which aims at a deepening of the studies for improvement of prevention of cancer in the country. HTML XML PDF
      PubDate: Thu, 24 Aug 2017 15:09:52 +030
  • Osteogenic, adipogenic and neurogenic differentiation of human
           adipose-derived mesenchymal stem cells before and after cryopreservation

    • Abstract: BioDiscovery 20: e20272
      DOI : 10.3897/biodiscovery.20.e20272
      Authors : Marina Hristova, Elena Hristova, Plamen Todorov : Mesenchymal stem cells (MSCs) represent a promising tool for the regeneration of damaged tissues in cell therapy. They are characterized as undifferentiated progenitors, which have the ability for self-renewal and multilineage differentiation potential. The development of effective protocols for long-term storage, with the aim of subsequent clinical usage, is essential for their application as cellular therapeutics. In our experiments, we aimed to investigate fresh and cryopreserved human adipose tissue-derived MSCs (AT-MSCs) and their osteogenic, adipogenic and neurogenic differentiation potential. The obtained results pointed out that the cells possess spindle-like shape and form characteristic wave-like layers when reaching confluency. The immunophenotypic analysis shows that they express CD73, CD90 and CD105 and lack the hematopoiеtic lineage markers CD34 and CD45. Both cryopreserved and fresh hAT-MSCs maintain similar ability to specialize towards osteogenic, adipogenic and neural lineage. In conclusion, the present study indicates that the isolated cells are cryotolerant and are able to retain their morphological and immunophenotypical characteristics  after freezing, as well as their multilineage differentiation potential. HTML XML PDF
      PubDate: Mon, 21 Aug 2017 23:16:27 +030
  • Two candidate genes for recurrent pregnancy loss and infertility: Could
           ZP3 and UPK3B give us new diagnostic and therapeutic approach'

    • Abstract: BioDiscovery 20: e20113
      DOI : 10.3897/biodiscovery.20.e20113
      Authors : Fatma Sılan, Baris Paksoy, Taner Karakaya, Onur Yildiz, Mine Urfali, Ozturk Ozdemir : Introduction: Chromosomal indels are relatively common cytogenetic abnormalities. Nonetheless, clinical outcomes depend on the location, size and genes in deletion or duplication regions. The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by ZP3(Zona pellucida3) gene is a structural component of the zona pellucida and functions in primary binding and induction of the sperm acrosome reaction. UPK3B(Uroplakin 3B), a minor component of the apical plaques of mammalian urothelium that binds and dimerizes with uroplakin-1b(UPK1B), one of the major conserved urothelium membrane proteins. We herein report two cases presenting with the deletions encompassing POMZP3, UPK3B, ZP3, POM121 and POM121C genes. Case1: 25-year-old female presented to our clinic with recurrent pregnancy loss. After clinical and cytogenetic evaluation, which all of them do not feature, she was diagnosed as the deletion of POMZP3 and UPK3B genes with the array-CGH platform. (Agilent SurePrintG3 HumanCGH 60K) Case2: Ten-week embrio of 34-year-old female, infertile for ten years before and this is her first pregnancy after IVF, revealed the deletion of POM121,POM121C and ZP3 genes with the same array-CGH platform. Conclusion: We have evaluated the deletion of two consecutive genes -UPK3B and ZP3- in the genome by array-CGH analysis. Early abortion or infertility due to triploidic, tetraploidic embryos or uniparental disomy, resulting in a change in the structure of the zona pellucida with the mutations of ZP3 gene, may occur. Also mutations of UPK3B gene may cause abortion or infertility due to endometrial origin with defective function of the urothelium membrane proteins. ICSI could be a good choice for ZP3 deficient infertile woman and if PGS choosen without ICSI, uniparental disomia should be excluded. HTML XML PDF
      PubDate: Thu, 10 Aug 2017 14:04:33 +030
  • Comet assay - a sensitive tool for genotoxicity assessment of
           environmental stress in Mytilus galloprovincialis from the Bulgarian Black
           Sea coast

    • Abstract: BioDiscovery 20: e19265
      DOI : 10.3897/biodiscovery.20.e19265
      Authors : Bela Vasileva, Lachezar Yakimov, Borislava Kukurina, Milena Georgieva, George Miloshev, Nesho Chipev : Assessment of DNA damage is of primary concern when the pollution-related stress in living organisms has to be determined. The reason for this concern comes from the evidence that damages in DNA often lead to mutations which are potential threat for the sustainability of organisms and ecological systems. To monitor genotoxicity of the marine environment we have developed a special procedure for application of the method of Comet assay (CA) on the native populations of Mytilus galloprovincialis. Samples were collected from areas with different anthropogenic load along the Bulgarian South Black Sea coast. As the first organ to encounter marine pollutants the gills of the mussels turned-out to be the most appropriate tissue for obtaining a single-cell suspension. Comet assay tests were performed and DNA damage was quantified using several different methods including percentage of DNA in the tail, Comet head and tail area, Comet number, Tail moment, Comet shape, etc. The method allowed us to monitor and predict the genetic risk of marine environmental stressors, particularly persistent pollutants. It proved to be convenient for precise quantification of the on-site loads of genotoxic stress on coastal ecosystems. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 22:58:49 +0300
  • Genetic changes in natural Taraxacum officinale populations obtained under
           pollution stress

    • Abstract: BioDiscovery 20: e18712
      DOI : 10.3897/biodiscovery.20.e18712
      Authors : Borislava Kukurina, George Miloshev : Plant populations under stress undergo genotypic alterations which can drive the species towards extinction or adaptation. Defining a suitable plant model and the respective genetic markers for studying the perturbations in the population’s genetic diversity is of crucial importance for the needs of bioconservation and proper ecosystem management. In the current study we prove the usefulness of Taraxacum officinale (common dandelion) as a suitable model plant for genetic biomonitoring. We compared the genotype composition of four specific dandelion populations: 1) a population from the area around the closed “Kremikovtzi” metallurgical plant; 2) a population from the still working “Stomana”-Pernik metallurgical facility; 3) a population from a rural, but naturally rich in heavy metals region close to Bosnek village; 4) a control population from a clean site next to Lokorsko village. Four genetic markers of tree different kinds (a microsatellite, a ribosomal DNA marker and two chloroplastic DNA markers) were tested in order to reveal the genotype diversity in the chosen populations. Our results showed strong quantitative and qualitative genotypic differentiation between pollution-impacted and clean populations. The most interesting observation was that the unique genotypes, considered as result of mutations, were predominantly detected in the plants from the heavy metal polluted regions. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 22:55:33 +0300
  • Basal and PGF2α-stimulated secretion of pro-inflammatory cytokines from
           3T3-L1 adipocyte-like cells

    • Abstract: BioDiscovery 20: e17757
      DOI : 10.3897/biodiscovery.20.e17757
      Authors : Bilyana Ilieva, Elena Marinova, Hristo Gagov, Rossitza Konakchieva : Adipocytes were recently identified as an important source of endocrine and paracrine mediators, regulating the metabolism and activity of various cell types and body functions. 3T3-L1 preadipocytes are useful model for physiological, pharmacological and cell signaling studies. Differentiation of 3T3-L1 murine fibroblasts into adipocyte-like cells was conducted in presence of IBMX, dexamethasone and insulin and demonstrated by Oil Red O staining of accumulated lipid droplets. Using Inflammatory Multi- Analyte Cytokines ELISArray Kit we investigated the release of cytokines under basal conditions, after PGF2α treatment for 24 hours to induce pro-inflammatory phenotype, and after PGF2α treatment and incubation in the presence of L-C-Propargylglycine (PGG, 1 mmol/l), a selective inhibitor of cystathionine-gamma-lyase (CSE). The last combination was used to explore the role of H2S, released from CSE, for cytokine and H2O2 release. We found that PGF2α strongly increased TNFα secretion from differentiated adipocytes, the latter effect being antagonized by PGG. The CSE inhibitor enhanced IL-6 production and suppressed IL-10 secretion. PGG enhanced H2O2 production of in PGF2α-treated cells. It is concluded that pro-inflammatory phenotype of differentiated 3T3-L1 adipocyte-like cells, induced by PGF2α is characterized by enhanced TNFα production which critically depends on the ability of CSE to produce H2S.  HTML XML PDF
      PubDate: Tue, 1 Aug 2017 19:14:03 +0300
  • Perivascular adipose tissue as regulator of the force of artery
           contractions in health and disease

    • Abstract: BioDiscovery 20: e19831
      DOI : 10.3897/biodiscovery.20.e19831
      Authors : Hristo Gagov, Radoslava Emilova, Daniela Dimitrova, Mitko Mladenov, Rudolf Schubert : During the last two decades, perivascular adipose tissue (PVAT) has been revealed as an important regulator of vascular processes such as proliferation of smooth muscle cells, pro- and anti-oxidant reactions in the vascular wall, angiogenesis, inflammation, apoptosis of neutrophils, migration of monocytes and others. PVAT derived mediators either increase or decrease the amplitudes of the force of artery contraction measured using isometric small vessel myography. In healthy animals and humans predominates the relaxing effect while in diseases the contractile influence of PVAT is common. In aging and pathological conditions like atherosclerosis and diabetes, or with environmental factors like tobacco smoke and high-fat diet, the phenotype of perivascular adipocytes is changed from anti-inflammatory to pro-inflammatory. This change is accompanied by a significant rearrangement of mediators released from PVAT. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 16:21:23 +0300
  • Ultrananocrystalline diamond coated implants for enhanced osseointegration

    • Abstract: BioDiscovery 20: e19830
      DOI : 10.3897/biodiscovery.20.e19830
      Authors : Silviya Stateva, Daniel Merker, Cyril Popov, Margarita Apostolova : Osteoporosis causes bones to become weak and brittle. It is known that the alterations in bone metabolism associated to osteoporosis can impair bone healing around implants and affect their osseointegration. The main objective of this study was the development of new nanostructured implant materials based on ultrananocrystalline diamond (UNCD) coatings for enhancing osseointegration. The films were deposited on Ti substrates by microwave plasma CVD from 17% CH4/N2 gas mixtures and modified by O2 or NH3/N2 plasmas. The modifications rendered the H-terminated hydrophobic as-grown films hydrophilic. The interaction of endothelial (EA.hy926) and osteosarcoma (MG63) cells with differently modified UNCD surfaces was investigated by proteome analyses. It revealed the identification of over 19 000 proteins (extracellular and cytosolic). They correspond to 508 (Ti), 634 (UNCD), 651 (O-UNCD), and 668 (NH2-UNCD) protein groups. The interaction network analysis showed differences in the connectivity of inferred protein networks between the ECM niches, which suggests the presence of specific cell microenvironments on O- and NH2-terminated UNCD surfaces. Our results show that due to a favorable combination of surface chemical and topological properties the UNCD films, as-grown and especially after their plasma modifications, may serve as superior scaffolding for promoting the cell attachment and growth during osseointegration. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 15:43:01 +0300
  • Testosterone as Diamine Oxidase Activity Regulator

    • Abstract: BioDiscovery 20: e17372
      DOI : 10.3897/biodiscovery.20.e17372
      Authors : Milena Mishonova, Hristo Gagov : Diamine oxidase (DAO) is a key enzyme of the metabolism of polyamines. Its activity was assayed in homogenate of male immature rat liver and kidney.  The androgens are important regulators of polyamines’ metabolism. It was known that testosterone (T) activates DAO in murine kidney, an effect that might depend on the intracellular level of polyamines. The aim of this research was to study the participation of androgen receptor and ornithine decarboxylase (ODC) in DAO testosterone regulation. The rats were treated i.p. 4 hours before measurements with T, T + Hydroxyflutamide (HF), an androgen receptor antagonist or T + difluoromethylornithine (DFMO), an inhibitor of ODC. It was observed that i) T significantly increased DAO activity of rat liver and kidney; ii) the presence of HF abolished the effect of T ; iii) the presence of DFMO slowly reduced the effect of T on DAO activity. It is concluded that T activates DAO mainly by a mechanism, which includes androgen receptor binding and ODC stimulation. HTML XML PDF
      PubDate: Tue, 1 Aug 2017 11:07:33 +0300
  • New Mechanisms of Perinatal Hypoxia and Perspectives of
           Pathogenesis-oriented Treatment

    • Abstract: BioDiscovery 20: e14945
      DOI : 10.3897/biodiscovery.20.e14945
      Authors : Larisa A. Balykova, Ludmila V. Ledyajkina, Vladimir A. Trofimov, Alexei P. Vlasov, Irina S. Nazarova, Victor V. Revin : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 23:16:45 +030
  • Change in morphometric and oxygen-binding properties of erythrocytes in
           vascular diseases patients

    • Abstract: BioDiscovery 20: e15079
      DOI : 10.3897/biodiscovery.20.e15079
      Authors : Natalia Gromova, Victor Revin, Nadezhda Revina, Anastasiya Kukina, Elvira Revina, Anastasiya Samonova , Ilya Solomadin, Alexander Tychkov, Inessa Moiseeva : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 20:57:38 +030
  • Antibacterial activity of thin films TiO2 doped with Ag and Cu on
           Gracilicutes and Firmicutes bacteria

    • Abstract: BioDiscovery 20: e15076
      DOI : 10.3897/biodiscovery.20.e15076
      Authors : Dragomira Stoyanova, Iliana Ivanova, Orlin Angelov, Todorka Vladkova : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 20:24:58 +030
  • Application of safe-by-design approach for curing osteoporosis – a
           lock at the future

    • Abstract: BioDiscovery 20: e15099
      DOI : 10.3897/biodiscovery.20.e15099
      Authors : Armine Grigoryan, Iliyan Kolev, Anelia Dimitrova, Margarita Apostolova : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 20:00:32 +030
  • Antiviral activity of Stachys Thracica Dav. extracts against Human Herpes
           virus type 1 and 2

    • Abstract: BioDiscovery 20: e15022
      DOI : 10.3897/biodiscovery.20.e15022
      Authors : Petya Angelova, Venelin Tsvetkov, Anton Hinkov, Daniel Todorov, Kalina Shishkova, Zhenya Yordanova, Veneta Kapchina-Toteva, Stoyan Shishkov : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 16:38:18 +030
  • Synthesis of a drug discovery library for the identification of sigma
           receptors modulators

    • Abstract: BioDiscovery 20: e14958
      DOI : 10.3897/biodiscovery.20.e14958
      Authors : Giacomo Rossino, Marta Rui, Marcello Di Giacomo, Daniela Rossi, Simona Collina : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 13:24:10 +030
  • Recent advances in the structure-guided research and development of
           antimicrobial therapeutics

    • Abstract: BioDiscovery 20: e14952
      DOI : 10.3897/biodiscovery.20.e14952
      Authors : Dimitar Trifonov, Tom Evers : HTML XML PDF
      PubDate: Mon, 17 Jul 2017 10:24:41 +030
  • Validation of a novel HPLC-based serum thymidine kinase assay for breast
           cancer detection

    • Abstract: BioDiscovery 20: e14563
      DOI : 10.3897/biodiscovery.20.e14563
      Authors : Elena Kuzmanova, Marilena Spanou, Emma Leckie, Nikolai Zhelev : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 5:44:23 +0300
  • A step forward in the identification of compounds interfering with the
           Embryonic Lethal Abnormal Vision (ELAV) protein - RNA complexes

    • Abstract: BioDiscovery 20: e14670
      DOI : 10.3897/biodiscovery.20.e14670
      Authors : Serena Della Volpe, Daniela Rossi, Francesca Vasile, Donatella Potenza, Marialaura Amadio, Alessia Pascale, Simona Collina : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 4:44:08 +0300
  • Sigma 1 receptor modulators as a new weapon against multiple sclerosis

    • Abstract: BioDiscovery 20: e14565
      DOI : 10.3897/biodiscovery.20.e14565
      Authors : Simona Collina, Marta Rui, Giacomo Rossino, Serena Della Volpe, Daniela Rossi, Arianna Scuteri, Alessio Malacrida, Guido Cavaletti : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 3:40:56 +0300
  • Cryogenic pretreatment of keratinous waste for enhanced methane production

    • Abstract: BioDiscovery 20: e14096
      DOI : 10.3897/biodiscovery.20.e14096
      Authors : Elena Kuzmanova, Joseph Akunna, Nikolai Zhelev : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 2:40:27 +0300
  • The effects of changes in composition and state of the lipids on
           erythrocytes’ oxygen-transport function in pathological conditions
           associated with the development of hypoxia

    • Abstract: BioDiscovery 20: e14701
      DOI : 10.3897/biodiscovery.20.e14701
      Authors : Victor V. Revin, Natalia V. Gromova, Elvira S. Revina, Ilya N. Solomadin, Alexander Yu. Tychkov : HTML XML PDF
      PubDate: Wed, 5 Jul 2017 1:39:59 +0300
  • Phosphorylase Kinase Inhibition Therapy in Burns and Scalds

    • Abstract: BioDiscovery 20: e11207
      DOI : 10.3897/biodiscovery.20.e11207
      Authors : Madalene Heng : Severe burns and scalds almost always result in unsightly hypertrophic scarring. Among the important processes involved in scarring are fibroblast formation and transformation of fibroblasts into myofibroblasts. Myofibroblasts contain α-smooth muscle actin which has contractile properties and can lead to wound contraction and hypertrophic scarring. Phosphorylase kinase (PhK), expressed within 5 mins of injury, is among the earliest enzymes released after tissue damage. It is responsible for activation of NF-kB, which in turn activates over 200 different genes related to inflammation, fibroblastic proliferation, myofibroblast conversion, and eventual scar tissue formation. The sequence and approximate timing of events following injury include the following: activation of PhK (5 mins), followed by appearance of neutrophils (30 mins), macrophages (hours to days), fibroblasts (1 week) and myofibroblasts (2 weeks). Cytokines and growth factors secreted by macrophages include fibroblast growth factor (FGF) and transforming growth factors α and β (TGFα and TGFβ). Fibroblast growth factor is responsible for fibroblastic proliferation, and TGFβ1 for conversion of fibroblasts into myofibroblasts. After thermal injury, the use of topical curcumin, a non-competitive, selective PhK inhibitor that blocks PhK activity upstream of NF-kB activation, was found to be associated with more rapid and improved skin healing, as well as less severe or absent scarring. HTML XML PDF
      PubDate: Fri, 24 Feb 2017 10:49:14 +020
  • Drug resistance of cancer cells is crucially affected by expression levels
           of ABC-transporters

    • Abstract: BioDiscovery 20: e11211
      DOI : 10.3897/biodiscovery.20.e11211
      Authors : Petr Mlejnek, Petr Dolezel, Eliska Ruzickova : Dasatinib (DAS), a second generation of tyrosine kinase inhibitor (TKI), represents excellent choice for the treatment of chronic myeloid leukemia resistant to imatinib. Unfortunately, recent laboratory studies suggested that antiproliferative effect of DAS might be significantly reduced due to the overexpression of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2. However, whether these drug transporters might compromise therapeutic effect of DAS in clinic is unclear. We believe that the drug transporter expression level is a crucial factor that affects the results and its consideration may help to explain the existing controversy. In addition, clinically relevant concentrations of drug must be used. In our study, human leukemia K562 cells with high and low expression levels of ABCB1 or ABCG2 were used. DAS was applied at nanomolar concentrations. We observed that K562 cells expressing high levels of ABCB1 and ABCG2 contained significantly reduced intracellular levels of DAS and these cells exhibited significantly increased resistance to this drug. Importantly, cells with the low expression of ABCB1 or ABCG2 effluxed DAS less efficiently, however, still significantly. Accordingly, the observed resistance was lower but significant. Conclusions: The antiproliferative effects of DAS might be reduced by ABCB1 or ABCG2. However, the actual effect of these ABC transporters on DAS efficiency depends on their expression levels. The lower expression levels of ABC transporters mediate lower resistance. Considering the fact that expression levels of ABCB1 and ABCG2 transporters are usually low in clinical samples, their contribution to the overall resistance to DAS is probably low but significant. HTML XML PDF
      PubDate: Wed, 8 Feb 2017 10:52:09 +0200
  • Screening an Archetypal Collection of Microorganisms for the Presence of
           Unexplored Antimicrobial Compounds

    • Abstract: BioDiscovery 20: e10763
      DOI : 10.3897/biodiscovery.20.e10763
      Authors : Lucia Cimarelli, Anna Maria Giuliodori, Anna Brandi, Karolina Adamkiewicz, Roberto Spurio, Attilio Fabbretti : HTML XML PDF
      PubDate: Wed, 8 Feb 2017 9:26:49 +0200
  • The success of stem cell transplantations and the potential
           post-transplantation complications may be dependent, among other factors,
           on the capacity of the recipient and the transplanted cells to repair DNA

    • Abstract: BioDiscovery 19: e9076
      DOI : 10.3897/BioDiscovery.19.e9076
      Authors : Lewis Reynolds : Cell therapy is presently a treatment of choice for many types of haematological and metabolic diseases and is likely to become a therapeutic option for other severe human diseases and conditions in the near future. The success of cell transplantation depends on a variety of factors, including the degree of HLA match between the donor and the recipient, the infectious burden of the graft, cell dosage, age, general state of the recipient and other incompletely characterised features of the donor and the recipient. It is likely that the individual capacity for identification and repair of DNA damage and maintenance of genomic integrity may account, at least in part, for these elusive factors that modulate transplantation outcome in terms of success rate and both long and short term post-transplantation complications. This paper outlines the role of individual repair capacity of the donor and recipient in cell transplantations, summarising the little knowledge already accumulated in the field whilst analysing the known major issues of the use of different types of stem cells. Attention will be given to their capacity to maintain the integrity of their genome, the ability to renew their own population, differentiate into various cell types and in some cases, succumb to carcinogenic transformation. Analysis of the individual capacity may become a useful tool in the assessment of the suitability of a set of freshly collected stem cells or an in vitro propagated cell line for potential clinical applications. HTML XML PDF
      PubDate: Tue, 29 Mar 2016 15:59:32 +030
  • An old wives' tale. Reproductive outcomes in pregnant women aged 35 or
           older: the role of individual repair capacity

    • Abstract: BioDiscovery 18: e8970
      DOI : 10.7750/BioDiscovery.2015.18.2
      Authors : Rumena Petkova, V Dimitrova, Nikolai Zhelev, Stoyan Chakarov : At present, childbirth is being progressively postponed until later age. Women aged 35 or older may have to wait longer to conceive than younger women and are more likely to be referred to fertility evaluations, but in a significant proportion a spontaneous conception would be achieved in the timeframe typical of younger women. Pregnancies where mothers are ≥ 35 are associated with more risks for pregnancy loss, chromosomal disease, pregnancy-associated complications, prematurity and low birthweight. These concerns, however, are not uncommon in younger women as well. This puts forward the question whether advanced age per se is the underlying cause for the increased risk for adverse outcomes in older pregnant women, or whether there might be other factors that account for it but do not radically worsen the prospects for favourable outcomes. The individual risks associated with childbirth late in life may stem from maternal genetic background rather than being a simple function of age. There is plenty of preliminary evidence that individual capacity for identification and repair of DNA damage may constitute a major factor in female fertility and fecundity. Subtle deficiencies in the repair capacity may have little to no importance in younger pregnant women but may make a significant difference in older women. The outcomes of pregnancies in women >35 are largely dependent on the pre-pregnancy health status and the quality of antenatal care, and may not be dramatically different from outcomes in younger women. HTML XML PDF
      PubDate: Wed, 23 Dec 2015 0:00:00 +0200
  • A de novo microdeletion 2p24.3-25.1 identified in a girl with global
           development delay

    • Abstract: BioDiscovery 18: e8967
      DOI : 10.7750/BioDiscovery.2015.18.1
      Authors : Hristo Y. Ivanov, Vili K. Stoyanova, Radoslava Vazharova, Aleksandar Linev, Ivan Ivanov, Samuil Ivanov, Lubomir Balabanski, Draga Toncheva : Interstitial microdeletions of the distal 2p are very rare. A small number of cases have been reported in the literature, involving regions 2p23-p25, 2p23-p24 and 2p24-p25. The most common symptoms involve: intrauterine growth retardation, developmental delay, mental retardation, microcephaly, craniofacial anomalies, musculoskeletal abnormalities, congenital heart defect and hearing impairment. Herein we report on a Caucasian girl, born after in vitro fertilization with discrete facial dysmorphism, growth failure, borderline neurodevelopment and congenital heart defect. A de novo pericentric inversion of chromosome 2 was identified by routine karyotyping. An interstitial microdeletion of 2p24.3p25.1 was found by array karyotyping and following FISH analysis revealed that the deletion affects the inverted chromosome 2. This case illustrates the utility of high resolution methods to identify submicroscopic quantitative changes in structurally rearranged chromosomes. The precise determination of the genetic content of small quantitative changes in the genome provides important information for genetic counseling, enabling to predict the course of disease and the planning of adequate therapy and prophylaxis in affected families. HTML XML PDF
      PubDate: Sat, 10 Oct 2015 0:00:00 +0300
  • Blood-Based Gene Expression in children with Autism spectrum disorder

    • Abstract: BioDiscovery 17: e8966
      DOI : 10.7750/BioDiscovery.2015.17.2
      Authors : Hristo Y. Ivanov, Vili K. Stoyanova, Nikolay T. Popov, M. Bosheva, Tihomir I. Vachev : Comparative gene expression profiling analysis is useful in discovering differentially expressed genes associated with various diseases, including mental disorders. Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although numerous autism susceptible genes were identified, the etiology of autism is not fully explained. The study aimed to examine gene expression profiling in peripheral blood from 60 individuals divided into two groups: children with ASD and age- and gender-matched healthy subjects (ASD control). A genome-wide sequencing of copy DNA molecules was conducted to obtain information for quantitative expression of all genes subject to this study and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis was used to further understand genes’ biological functions. Based on the conducted expression analysis 23 differentially expressed genes and 21 KEGG signaling pathways with statistical significant change were identified. Blood-based comparative gene expression profiling analysis is useful in discovering genetic markers associated with ASD. Our data will provide a valuable resource for discovery purposes and for comparison to other gene expression-based, genome-wide studies and other functional data. HTML XML PDF
      PubDate: Wed, 30 Sep 2015 0:00:00 +0300
  • APOE4, oxidative stress and decreased repair capacity - a no-brainer.
           Faulty lipid metabolism and increased levels of oxidative damage may be
           risk factors in the pathogenesis of late-onset dementia

    • Abstract: BioDiscovery 17: e8969
      DOI : 10.7750/BioDiscovery.2015.17.1
      Authors : Ashima Nayyar, Lubomira Chakalova : Dementia is very common in the elderly and its incidence increases in an age-dependent fashion. Alzheimer''s disease and vascular cognitive decline are the most common cases of dementia in the elderly. Amyloid burden and increased levels of oxidative damage have been implicated to play significant roles in the pathogenesis of late-onset dementia. In this paper we propose that there are three major genetic factors that may modulate the risk for dementia in later life: carriership of <em>APOE</em> variant alleles, carriership of mitochondrial DNA of haplogroups associated with ineffective oxygen utilisation (specifically, haplogroup H) and carriership of genetic polymorphisms conferring subtly deficient DNA repair. All three factors are quite common in the European populations. Each of these three factors may not have significant effect on the phenotype when taken separately, but when combined in the same genotype, the effects may be cumulative. Further studies are needed in order to elucidate the genotype-phenotype relationships and provide a reliable basis for assessment of the genetic risk for sporadic late-onset dementia. Lifestyle alterations and therapies targeted at decreasing the oxidative burden to aging cells and tissues may decrease the risk for neurological decline in later life. HTML XML PDF
      PubDate: Thu, 24 Sep 2015 0:00:00 +0300
  • Human pluripotent stem-cell-derived cardiomyocytes in cardiovascular drug
           discovery and development

    • Abstract: BioDiscovery 16: e8965
      DOI : 10.7750/BioDiscovery.2015.16.1
      Authors : Kirsty Lewis, Kerry Falconer : Cardiovascular disease (CVD) is an alarming health problem responsible for a large percentage of fatality worldwide. Current treatment is limited and research is ongoing to address this serious health problem. As mortality rates rise, the demand for novel therapeutics has pressed the pharmaceutical industry to explore alternative approaches for CVD drug development. Human pluripotent stem cells (hPSCs) hold great promise in bringing new effective cardiovascular treatments to the market through providing an improved testing platform for pre-clinical drug screening. Both stem cells derived from pre-implantation human embryos or somatic cells by reprogramming are under intense investigation for their potentially valuable attributes of cell renewal and pluripotency. This approach aims to overcome the lack of appropriate human cardiac disease models for toxicology testing by providing a novel system that is scalable, reproducible and from an inexhaustible source. Here we review the opportunities for cardiomyocytes derived from human stem cells in the field of cardiovascular drug development. HTML XML PDF
      PubDate: Sun, 28 Jun 2015 0:00:00 +0300
  • Small molecules and human cardiomyogenesis: Is there a bottleneck in
           current research'

    • Abstract: BioDiscovery 15: e8968
      DOI : 10.7750/BioDiscovery.2015.15.2
      Authors : Dimitar Trifonov : Human pluripotent stem cell derived cardiomyocytes (hPSC-derived CMs) have a vast potential in drug discovery, disease modeling and regenerative medicine. In recent years various differentiation protocols for hPSC-derived CMs have been developed. Most of them utilize the modulation of human cardiomyogenesis via small-molecule compounds. However, setbacks to the large-scale application of hPSC-derived CMs still abound: insufficient insight into important signaling pathways for cardiac lineage-specific differentiation and identification of suitable small-molecule modulators; inconsistent results due to unstandardised culturing techniques; lack of effective maturation of hPSC-derived CMs in vitro. So is there a bottleneck in current research' This paper attempts to answer this question. HTML XML PDF
      PubDate: Tue, 31 Mar 2015 0:00:00 +0300
  • NRF2 inhibition causes repression of ATM and ATR expression leading to
           aberrant DNA Damage Response

    • Abstract: BioDiscovery 15: e8964
      DOI : 10.7750/BioDiscovery.2015.15.1
      Authors : Hilal S Khalil, Yusuf Deeni : Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a master regulator of the antioxidant response (AR) pathway and functions as a transcription factor for basal and oxidative stress-induced expression of a battery of detoxification enzymes and cytoprotective genes. Recent evidence has also demonstrated a role of NRF2 in driving resistance of numerous cancers to chemotherapeutic agents. ATM and ATR are serine/threonine kinases that are activated following DNA damage and function as central components of DNA Damage Response (DDR) pathway. Activities of these kinases cause cell cycle arrest and activate DNA repair signals leading to cytoprotection against genotoxic agents. In this study, we elucidated the roles of ATM- and ATR- dependent DDR and NRF2- mediated AR pathways in promoting cytoprotection following cisplatin challenge in ovarian cancer cell line models. We also determined whether these pathways were inter-dependent for full activation following genotoxic insults and as such demonstrated crosstalk in their signaling mechanism to elicit cytoprotective pathways. Treatment with cisplatin caused NRF2 induction and generation of reactive oxygen species (ROS) that caused cytotoxicity in ovarian cancer cells. This was attenuated by the ROS scavenger N-Acetyl cysteine, implicating NRF2 function in cytoprotection against cisplatin. Treatment with retinoic acid (RA) caused down regulation of NRF2, disruption of AR pathway, significant accumulation of ROS and enhanced cisplatin cytotoxicity. Interestingly, RA treatment also led to repression of total ATM and ATR proteins and aberrant DDR activation following cisplatin challenge. In order to determine whether the RA induced ATM and ATR repression was dependent on NRF2 inhibition, we silenced NRF2 using SiRNA. This caused transcriptional repression of both <em>ATM</em> and <em>ATR</em> expression as determined by their promoter driven luciferase assays. Thus, NRF2 inhibition led to DDR suppression by down-regulating ATM and ATR that led to enhanced cytotoxicity. These findings demonstrate mechanism of crosstalk between the AR and the DDR pathways and extend the scope of NRF2 in promoting cancer therapeutic resistance. HTML XML PDF
      PubDate: Sat, 28 Mar 2015 0:00:00 +0200
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