imagine (Institute of molecular genetics and genetic engineering)
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Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients
Get PDFIntroduction: The finding that long noncoding RNAs (lncRNAs) originating from tumor cells could be found in general circulation has prompted the idea to use lncRNAs as noninvasive diagnostic biomarkers of particular diseases. In this study we explored the expression pattern of circulating GAS5..
Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD
Get PDFPatients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus and patient clinical phenotype. This is especially effective for the study of patients with neurodevelopmental disorders (NDD), including those falling within the autism spectrum disorders (ASD). A key question is whether this correlation between genetics and clinical presentation at the level of the patient can be translated to the cell phenotypes arising from the neurodevelopment of patient induced pluripotent stem cells (iPSCs). Here, we examine how iPSCs derived from ASD patients with an associated CNV inform our understanding of the genetic and biological mechanisms underlying the aetiology of ASD. We consider selection of genetically characterised patient iPSCs; use of appropriate control lines; aspects of human neurocellular biology that can capture in vitro the patient clinical phenotype; and current limitations of patient iPSC-based studies. Finally, we consider how future research may be enhanced to maximise the utility of CNV patients for research of pathological mechanisms or therapeutic targets
Impact of pollution on rivers in Montenegro: Ecotoxicological perspective
No full textMontenegrin surface water and groundwater are important for the Balkan Peninsula since they are connected by the transboundary Dinaric Karst Aquifer System with the waters of additional five countries. The pollution from the surface water can rapidly infiltrate in aquifer and endanger this sensible ecosystem and the health of humans through drinking water supply. This chapter gives insights in the pressures of pollution on Montenegrin waters and in a limited literature data regarding freshwater ecotoxicological studies in Montenegro. Also, this chapter provides new ecotoxicological data obtained during survey in 2019, with a focus on the sites which are identified as hotspots of fecal pollution. The highest responses of biomarkers which indicate embryotoxic, genotoxic, and phytotoxic effects in zebrafish embryo test and in roots of Allium cepa were obtained at Ćehotina – downstream of Pljevlja. Similar results were detected at the site downstream Mojkovac at Tara, yet this site is affected by different type of pollution. Genotoxic endpoints in zebrafish stressed out sites on Morača and Lim rivers which are under pressures of fecal pollution. The data in this chapter provides an insight into current status obtained by the ex situ bioassays and indicates need for more comprehensive in situ assessment
Phylogeographic and taxonomic considerations on Goniolimon tataricum (Plumbaginaceae) and its relatives from south-eastern Europe and the Apennine Peninsula
No full textGoniolimon species are mainly components of the Eurasian steppe or steppe-like rocky vegetation, with some taxa occurring also in south-eastern Europe and northern Africa. We analysed the variability of: (i) two maternally inherited plastid loci (rpl32-trnL and 3 ' rps16-5 ' trnK) in 110 individuals of six currently accepted species from the Balkans and one species from the Apennines, to provide new insights into their origin and evolutionary history; and (ii) quantitative morphological characters (14 independent characters and one ratio character) in 641 individuals of three species of which two are morphologically and ecologically similar (G. italicum and G. tataricum) and the third, G. dalmaticum, was frequently misidentified as G. tataricum in the past, to provide new taxonomic treatment for proposed G. tataricum subspecies. We delineated several quantitative and five qualitative characters studied in a more limited sample as diagnostic for the identification of four subspecies (three newly described and one in a new rank) of G. tataricum. The history of westward peripheral populations of this species in the Balkans and the Apennines was rather complex and driven by local geo-historic events. These events facilitated multiple waves of east-west expansion of lineages originating from sources outside of the Balkan Peninsula which periodically diversified and occupied localised areas in the Balkans during the Pleistocene. An initial spread of an ancient G. tataricum lineage throughout south-eastern Europe probably occurred during the Messinian Salinity Crisis. Inter- and intraspecific hybridisation/introgression, as well as retention of ancestral polymorphisms, was common in G. tataricum and related taxa over time
Polynuclear Silver(I) Complex with Thianthrene: Structural Characterization, Antimicrobial Activity and Interaction with Biomolecules
Get PDFNew silver(I) complex with thianthrene (tia), [Ag(NO3)(tia)(H2O)]n, was synthesized by the reaction of AgNO3 with an equimolar amount of tia in ethanol/dichloromethane (v/v 1:1) at room temperature, and characterized by NMR, IR and UV-Vis spectroscopy and single-crystal X-ray diffraction analysis. The antimicrobial activity of the synthesized complex was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and Candida spp. This complex showed significant activity toward important human pathogens Gram-positive Staphylococcus aureus and Candida parapsilosis with minimal inhibitory concentrations (MICs) being 3.91 µg/mL. The interaction of [Ag(NO3)(tia)(H2O)]n with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate the binding affinity towards these biomolecules for possible insights on the mode of antimicrobial activity. The binding affinity of the investigated complex to BSA is higher than that for DNA, indicating that proteins could be more favorable binding sites for this complex in comparison to the nucleic acids
Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression
No full textAcinetobacter baumannii je globalno rasprostranjen nozokomijalni patogen koji se odlikuje izuzetnom sposobnošću ekstremno brzog sticanja rezistencije na antibiotike, kao i adaptacije na preživljavanje u suvim uslovima bolničke sredine [1]. Zbog velike zastupljenosti rezistentnih sojeva protiv kojih ne postoji delotvorna terapija, Svetska zdravstvena organizacija (WHO, 2017) i Centri za kontrolu i prevenciju bolesti (CDC, 2019), označili su A. baumannii kao patogen od kritične važnosti za otkriće novih antimikrobnih agenasa ili novih terapijskih strategija [2]. Targetiranje virulencije je oblik alternativnog terapijskog pristupa koji pruža mogućnost prevencije teže kliničke slike kod inficiranih pacijenata posredstvom inhibicije ekspresije ključnih faktora virulencije, uz istovremenu redukovanu selekciju rezistentnih mutanata [3].Rezultati i Diskusija: Od četiri različito supstituisana hidroksihalkona, sintetisanih u postupku bazno-katalizovane Claisen-Schmidt kondenzacije, selektiran je metkosi-supstituisani derivat kao najpotentniji inhibitor produkcije biofilma kod A. baumannii. Primenom Real-Time kvantitativne PCR metode sa reverznom transkriptazom ispitan je uticaj subinhibitornih koncentracija selektiranog jedinjenja (70, 35 i 10 μg/mL) na ekspresiju gena faktora virulencije povezanih sa produkcijom biofilma kod A. baumannii: ompA, bap i abaI. Pokazana je značajna dozno-zavisna nishodna ekspresija ompA gena, koji kodira OmpA protein spoljašnje membrane ćelijskog zida, koji učestvuje u brojnim virulentnim osobinama A. baumannii, kao što su adhezija, citotoksičnost, motilitet i rezistencija na imunski odgovor i antibiotike [4]. Takođe, zabeležena je značajna inhibicija ekspresije bap gena, koja je neophodna za adheziju na humane epitelne ćelije, i abaI gena, integralnog dela bakterijskog kvorum-sensing sistema, koji kodira sintazu autoinduktorskih molekula. Sposobnost antivirulentnog delovanja metoksi-supstituisanog derivata hidroksihalkona potvrđena je demonstracijom inhibicije fenotipske ekspresije faktora virulencije povezanih sa ekspresijom ompA, bap i abaI gena, kao što su adhezija za komponente ekstracelularnog matriksa (fibronektin i kolagen), površinski motilitet i produkcija autoinduktorskih molekula.Zaključak: Metoksi-supstituisani hidroksihalkon ispoljava antivirulentno dejstvo protiv A. baumannii, pre svega posredstvom nishodne regulacije ompA gena, što se reflektuje u inhibiciji produkcije biofilma, sposobnosti adhezije i površinskog motiliteta ovog patogena.Over the last two decades, Acinetobacter baumannii has emerged as one of the most troublesome pathogens, rapidly acquiring resistance to virtually all available antibiotics. This has urged researchers to seek alternative ways to fight this pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm activity of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. We used quantitative Real-Time PCR to evaluate mRNA expression of virulence-associated genes (ompA, bap, abaI) in extensively drug-resistant (XDR) A. baumannii wound isolate and A. baumannii ATCC 19606 strain, treated with selected compound. Also, we tested biofilm production, fibronectin- and collagen-mediated adhesion, surface motility and quorum-sensing activity of treated strains. The results revealed downregulation of the expression of all tested virulence genes together with the reduction of biofilm production, adhesion and motility. The most notable finding is significant reduction of ompA gene expression, whose encoded protein product is associated with numerous virulence traits of A. baumannii. Therefore, we conclude that selected methoxy-substituted hydroxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of the bacterial adhesins, most importantly OmpA, which is reflected in reduced biofilm formation, adhesion and surface motility.Conference: [https://www.morressier.com/event/femsonline2020/5f33917158e720f5e5546bb7]Related to the article: [http://dx.doi.org/10.1002/cbdv.202000786]Related to accepted version: [https://imagine.imgge.bg.ac.rs/handle/123456789/2821]Related to supp. material: [https://imagine.imgge.bg.ac.rs/handle/123456789/2822
Supplementary data for the article: Vidović, M.; Franchin, C.; Morina, F.; Veljović-Jovanović, S.; Masi, A.; Arrigoni, G. Efficient Protein Extraction for Shotgun Proteomics from Hydrated and Desiccated Leaves of Resurrection Ramonda Serbica Plants. Anal Bioanal Chem 2020, 412 (30), 8299–8312. https://doi.org/10.1007/s00216-020-02965-2.
Get PDFSupplementary material for: [https://doi.org/10.1007/s00216-020-02965-2]Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1364
Photoactivatable Surface-Functionalized Diatom Microalgae for Colorectal Cancer Targeted Delivery and Enhanced Cytotoxicity of Anticancer Complexes
Get PDFSystemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and characterization of a bio-inspired hybrid multifunctional drug delivery system based on diatom microalgae. The microalgae's surface was chemically functionalized with hybrid vitamin B-12-photoactivatable molecules and the materials further loaded with highly active rhenium(I) tricarbonyl anticancer complexes. The constructs showed enhanced adherence to colorectal cancer (CRC) cells and slow release of the chemotherapeutic drugs. The overall toxicity of the hybrid multifunctional drug delivery system was further enhanced by photoactivation of the microalgae surface. Depending on the construct and anticancer drug, a 2-fold increase in the cytotoxic efficacy of the drug was observed upon light irradiation. The use of this targeted drug delivery strategy, together with selective spatial-temporal light activation, may lead to lower effective concentration of anticancer drugs, thereby reducing medication doses, possible side effects and overall burden for the patient
Reaction of a 3-aryilidene-2-thiohydantoin derivative with polymeric trans-[CuCl2(DMSO)(2)](n) complex: unexpected isomerization to dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2)
Get PDFThe 3-arylidene-2-thiohydantoin derivative, 3-[(2-hydroxybenzylidene)amino]-2-thioxoimidazolidin-4-one, was synthesized in a two-step condensation reaction of 2-hydroxybenzaldehyde, thiosemicarbazide and ethyl chloroacetate. The ligand was structurally characterized by NMR and IR spectroscopy, as well as by elemental analysis. In the reaction of the well-known polymeric trans-[CuCl2(DMSO)(2)](n) complex with the polydentate thiohydantoin type ligand, instead of the corresponding copper thiohydantoin complex, unexpectedly, the dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2) complex (1) was formed predominantly as the final stable product. The structure of the complex 1 was confirmed by single crystal X-ray diffraction analysis. The cis-complex is obtained through assisted isomerization of the trans-form, in which the thiohydantoin derivative has a crucial role
Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients
No full textFludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high-expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients