imagine (Institute of molecular genetics and genetic engineering)
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Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters
The biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on many factors like the presence of appropriate ligands. Studies on anticancer activity of cadmium complexes showed that the complexation of various ligands resulted in complexes that showed better activities than approved drugs. In the present study, cadmium complexes with biologically potent thiazolyl/selenazoyl-hydrazone ligands have been prepared, and tested for their activity against different types of tumor cell models. The complexation of ligands with Cd(II) resulted in a synergistic effect. The antiproliferative activity study revealed that all complexes are more active compared to 5-fluorouracil and cisplatin. The mechanism of tumor cell growth inhibition reveal that selenium-based compounds induce cell death in T-47D (gland carci-noma) cells through apoptosis via caspase-3/7 activation. Additionally, their pro-apoptotic effect was stronger compared to etoposide and cisplatin. Nuclease activity, detected by gel electrophoresis, may be the possible mechanism of anticancer action of investigated complexes
Die Wirkung der Ergänzung von Kastanien-Tanninen auf die Produktionsergebnisse von Lämmern bei Proteinmangelrationen
The aim of this study was to investigate the effects of chestnut tannins in metabolizable protein deficiency, on dry matter (DM) intake, growth performance of finishing lambs, feed efficiency and digestibility of nutrients. The study included 30 crossbred lambs, blocked by body weight (BW) and divided into three groups, depending on the concentrations of added chestnut tannins in the rations (0, 10 and 20 g/kg DM for CON, 10T and 20T group, respectively). Rations were determined by BW and expected average daily gain (ADG), with a deficiency in metabolizable protein of about 15%. All groups received the same amount of daily feed. Dry matter intake, ADG and indicators of efficiency such as the Kleiber ratio (KR) and protein efficiency ratio (PER) were estimated. The digestibility of the rations was determined in three collection periods. Dry matter intake did not differ among groups. Growth performances for the whole experiment were significantly better for the 20T group than CON (p lt 0.05), while no differences were established for group 10T. Group 20T achieved the highest ADG and total gain (228 g/day +/- 27.8; 13.7 kg +/- 1.7), with the best average conversion of dry matter (4.4 kg DM/kg BW), KR (15.6), and PER (1.6). In all three collections, dry matter and crude protein digestibility was higher for CON, while the digestibility of ether extract was higher for the 20T group than CON. Based on these results, it can be concluded that a ration of chestnut tannins in the concentration of 20 g/kg DM, in conditions of protein deficiency, can have a positive effect on lamb performances. This can be partially explained by the ability of tannins to form complexes with proteins, which can change intestinal protein flow and utilization.Das Ziel dieser Studie war, die Wirkungen von Kastanien-Tanninen in Rationen mit
unzureichender Versorgung mit metabolisierbarem Protein auf die Aufnahme von
Trockenmasse (DM), die Wachstumsleistung von Mastlämmern, den Futteraufwand und die Verdaulichkeit von Nährstoffen zu untersuchen. Die Studie umfasste 30 Kreuzungslämmer,
die durch das Körpergewicht (BW) und die Konzentrationen von zugesetzten
Kastanien-Tanninen in der Nahrung (0, 10 und 20 g/kg DM für die Kontrolle, 10T- bzw.
20T-Gruppe) in drei Gruppen unterteilt wurden. Die Rationen wurden durch das Körpergewicht
(BW) und die erwartete durchschnittliche tägliche Zunahme (ADG) mit einem
Mangel an metabolisierbarem Protein von etwa 15% definiert. Alle Gruppen erhielten
die gleichen Futtermengen. Die DM-Aufnahmen, ADG-Werte, und Verwertungsgrößen
wie das Kleiber-Verhältnis (KR) und das Protein-Effizienz-Verhältnis (PER) wurden
geschätzt. Die scheinbare Verdaulichkeit wurde in drei Sammelperioden ermittelt. Die
DM-Aufnahme unterschied sich nicht zwischen den Gruppen. Die Wachstumsleistungen
für das gesamte Experiment waren für die 20T-Gruppe signifikant besser als für die
Kontrollgruppe (p < 0,05), während für die 10T-Gruppe keine Unterschiede festgestellt
wurden. Gruppe 20T erreichte den höchsten ADG und Gesamtzuwachs (228 g/Tag
± 27,8; 13,7 kg ± 1,7) mit der besten durchschnittlichen Umwandlung von Trockenmasse
(4,4 kg DM/kg BW) und den günstigsten Werten für KR (15,6) und PER (1,6). In allen
drei Sammelperioden war die Verdaulichkeit von DM und Rohprotein bei der Kontrolle
höher, während die Verdaulichkeit des Rohfetts bei der 20T-Gruppe höher war als bei der
Kontrolle. Aus den Ergebnissen kann geschlossen werden, dass Kastanientannine in
einer Konzentration von 20 g/kg DM Futter bei Proteinmangel einen positiven Effekt auf
die Leistung von Mastlämmern haben können. Dies kann teilweise durch die Fähigkeit
von Tanninen erklärt werden, Komplexe mit Proteinen zu bilden, die den Proteinfluss
durch den Verdauungstrakt und seine Verwertung verändern können
Native Non-Saccharomyces Yeasts as a Tool to Produce Distinctive and Diverse Tamjanika Grape Wines
The enological potential of two previously characterized indigenous yeast isolates, Hanseniaspora uvarum S-2 and Candida famata WB-1, in pure and sequential inoculation with commercial yeast Saccharomyces cerevisiae QA23 were analyzed in industrial-scale vinification of the grape variety Tamjanika. Their contribution to the quality and aroma profile was investigated by quantifying volatile compounds and wine sensory evaluation. Both yeast isolates were able to complete alcoholic fermentation, to reduce ethanol concentration up to 1.06% v/v (in monoculture) in comparation to S. cerevisiae QA23, and to enhance aroma and sensory profile. Based on calculated odor activity values (OAV), p-cymene, ethyl hexanoate, ethyl octanoate, and ethyl decanoate were the major aroma volatile compounds in all Tamjanika wine samples. Analyzed yeast strains significantly affected relative contribution of volatile compounds and can be considered responsible for the differences and uniqueness of the obtained wine samples. Besides confirmation of good enological and fermentative characteristics, selected isolates can be characterized as high ester-producing strains with potential to enhance the floral and fruity aromas of wine. The present study represents a further step toward the use of indigenous yeast isolates at industrial-scale fermentation in order to ensure the regional signature of Tamjanika wine
Chemical engineering methods in analyses of 3d cancer cell cultures: hydrodynamic and mass transport considerations
A multidisciplinary approach based on experiments and mathematical modeling was used in biomimetic system development for three-dimensional (3D) cultures of cancer cells. Specifically, two cancer cell lines, human embryonic teratocarcinoma NT2/D1 and rat glioma C6, were immobilized in alginate microbeads and microfibers, respectively, and cultured under static and flow conditions in perfusion bioreactors. At the same time, chemical engineering methods were applied to explain the obtained results. The superficial medium velocity of 80 mu m s(-1) induced lower viability of NT2/D1 cells in superficial microbead zones, implying adverse effects of fluid shear stresses estimated as similar to 67 mPa. On the contrary, similar velocity (100 mu m s(-1)) enhanced the proliferation of C6 glioma cells within microfibers compared to static controls. An additional study of silver release from nanocomposite Ag/honey/alginate microfibers under perfusion indicated that the medium partially flows through the hydrogel (interstitial velocity of similar to 10 nm s(-1)). Thus, a diffusion-advection-reaction model described the mass transport to immobilized cells within microfibers. Substances with diffusion coefficients of similar to 10(-)(19)-10(-11) m(2) s(-)(1) are sufficiently supplied by diffusion only, while those with significantly lower diffusivities (similar to 10(-1)(9) m(2) s(-1)) require additional convective transport. The present study demonstrates the selection and contribution of chemical engineering methods in tumor model system development
Bacterial nanocellulose as green support of platinum nanoparticles for effective methanol oxidation
Bacterial nanocellulose, BNC, has emerged as a new class of nanomaterials recognized as renewable, biodegradable, biocompatible and material for versatile applications. BNC also proved as a perfect support matrix for metallic nanoparticle synthesis and appeared as suitable alternative for widely used carbon based materials. Following the idea to replace commonly used carbon based materials for platinum supports with the green and sustainable one, BNC appeared as an excellent candidate. Herein, microwave assisted synthesis has been reported for the first time for platinum nanoparticles supported on BNC as green material. Bacterial nanocelullose-platinum catalyst, Pt/BNC, was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), atomic force microscopy (AFM), X-ray diffractometry (XRD) and transmission-electron microscopy (TEM) analysis. The obtained results confirmed successful synthesis of new Pt-based catalyst. It was found that Pt/BNC catalyst has high electrocatalytic performance in methanol oxidation reaction. Green/sustainable catalytic system is highly desirable and provided by the elegant microwave assisted synthesis of Pt/BNC will pave the way for a larger scale application and expedite the market penetration of such fuel cells.This is the peer reviewed version of the paper: M. Ponjavic, S. Stevanovic, J. Nikodinovic-Runic, et al., Bacterial nanocellulose as green support of platinum nanoparticles for effective methanol oxidation, International Journal of Biological Macromolecules (2022), [https://doi.org/ 10.1016/j.ijbiomac.2022.10.278
Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia
Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered
The Significance of MGMT Promoter Methylation Status in Diffuse Glioma
A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O6-methylguanine-DNA methyltransferase (MGMT). Younger patients (50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p ≈ 0.05). The OS of the hypermethylated group was 9.6 ± 1.77 months, whereas the OS of the unmethylated group was 5.43 ± 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required
In Vitro and In Vivo Biocompatible and Controlled Resveratrol Release Performances of HEMA/Alginate and HEMA/Gelatin IPN Hydrogel Scaffolds
Scaffold hydrogel biomaterials designed to have advantageous biofunctional properties, which can be applied for controlled bioactive agent release, represent an important concept in biomedical tissue engineering. Our goal was to create scaffolding materials that mimic living tissue for biomedical utilization. In this study, two novel series of interpenetrating hydrogel networks (IPNs) based on 2-hydroxyethyl methacrylate/gelatin and 2-hydroxyethyl methacrylate/alginate were crosslinked using N-ethyl-N′-(3-dimethyl aminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Characterization included examining the effects of crosslinker type and concentration on structure, morphological and mechanical properties, in vitro swelling, hydrophilicity as well as on the in vitro cell viability (fibroblast cells) and in vivo (Caenorhabditis elegans) interactions of novel biomaterials. The engineered IPN hydrogel scaffolds show an interconnected pore morphology and porosity range of 62.36 to 85.20%, favorable in vitro swelling capacity, full hydrophilicity, and Young’s modulus values in the range of 1.40 to 7.50 MPa. In vitro assay on healthy human fibroblast (MRC5 cells) by MTT test and in vivo (Caenorhabditis elegans) survival assays show the advantageous biocompatible properties of novel IPN hydrogel scaffolds. Furthermore, in vitro controlled release study of the therapeutic agent resveratrol showed that these novel scaffolding systems are suitable controlled release platforms. The results revealed that the use of EDC and the combination of EDC/NHS crosslinkers can be applied to prepare and tune the properties of the IPN 2-hydroxyethyl methacrylate/alginate and 2-hydroxyethyl methacrylate/gelatin hydrogel scaffolds series, which have shown great potential for biomedical engineering applications
Цитотоксични потенцијал естара линолеинске киселине детектованих у одбрамбеним секретима стонога Megaphyllum bosniense и M. unilineatum (Diplopoda: Julida)
Najveći broj stonoga iz klase Diplopoda poseduje hemijsku zaštitu od predatora
i/ili patogenih mikroorganizama, koji podrazumeva prisustvo odbrambenih
žlezda (ozadena) na trupu čiji se sekreti izbacuju u spoljašnju sredinu preko
otvora koji se naziva ozopora. Predstavnici reda Julida su poznati po tome da su
najčešće dominantne komponente njihovih odbrambenih sekreta hinoni. Pored
hinona, u sekretima ozadena Julida registrovani su i alkoholi, aldehidi, ketoni,
fenolna jedinjenja, kao i brojni estri zasićenih i nezasićenih karboksilnih
kiselina. Dosadašnja istraživanja su pokazala da su ekstrakti odbrambenih
sekreta Julida, kao i pojedinačna jedinjenja koja u njihov sastav ulaze, biološki
aktivni prirodni proizvodi, ali njihov citotoksični potencijal nije dovoljno
istražen. U ovoj studiji je ispitivan uticaj različitih estara linoleinske
kiseline (butil-, pentil-, heksil-, heptil-, oktil-, nonil-, fenetil- i 3-
fenilpropil-linoleat) detektovanih u odbrambenim sekretima stonoga
Megaphyllum bosniense i M. unilineatum na vijabilnost normalnih (BEAS-2B) i
kancerskih (A549) ćelija pluća korišćenjem MTT testa. Svi ispitivani estri su
smanjivali vijabilnost ćelija, pri čemu je postojala značajna razlika u odgovoru
kancerskih u odnosu na normalne ćelije u slučaju tri estra (heksil-, fenetil- i 3-
fenilpropil-linoleat). Iako su estri karboksilnih kiselina poznati kao malo
reaktivna jedinjenja, rezultati ove studije pokazuju da predstavnici ove klase
hemijskih jedinjenja mogu imati citotoksični potencijal.Највећи број стонога из класе Diplopoda поседује хемијску заштиту од предатора
и/или патогених микроорганизама, који подразумева присуство одбрамбених
жлезда (озадена) на трупу чији се секрети избацују у спољашњу средину преко
отвора који се назива озопора. Представници реда Julida су познати по томе да су
најчешће доминантне компоненте њихових одбрамбених секрета хинони. Поред
хинона, у секретима озадена Julida регистровани су и алкохоли, алдехиди, кетони,
фенолна једињења, као и бројни естри засићених и незасићених карбоксилних
киселина. Досадашња истраживања су показала да су екстракти одбрамбених
секрета Julida, као и појединачна једињења која у њихов састав улазе, биолошки
активни природни производи, али њихов цитотоксични потенцијал није довољно
истражен. У овој студији је испитиван утицај различитих естара линолеинске
киселине (бутил-, пентил-, хексил-, хептил-, октил-, нонил-, фенетил- и 3-
фенилпропил-линолеат) детектованих у одбрамбеним секретима стонога
Megaphyllum bosniense и M. unilineatum на вијабилност нормалних (BEAS-2B) и
канцeрских (A549) ћелија плућа коришћењем МТТ теста. Сви испитивани естри су
смањивали вијабилност ћелија, при чему је постојала значајна разлика у одговору
канцерских у односу на нормалне ћелије у случају три естра (хексил-, фенетил- и 3-
фенилпропил-линолеат). Иако су естри карбоксилних киселина познати као мало
реактивна једињења, резултати ове студије показују да представници ове класе
хемијских једињења могу имати цитотоксични потенцијал.Knjiga sažetaka: Treći Kongres biologa Srbije, Zlatibor, Srbija 21 - 25. 9. 2022
Од отпада до биотерапеутика
Iako su bioterapeutici doveli do revolucionarnih promena u lečenju raka,
dokazali svoju efikasnost u saniranju mikrobnih infekcija i lečenju ljudi sa
retkim bolestima, zbog visoke cene nisu svima dostupni. Inovativni pristup gde
otpad ulazi u sastav hranjivih podloga za gajenje bakterija bi mogao dovesti do
smanjenja cene bioterapeutika. Fermentacijom na skali od 5 L je dobijeno
nekoliko bioaktivnih prirodnih proizvoda, pri čemu je različit otpad bio izvor
hranjivih materija za gajenje mikroorganizama proizvođača. Prodigiozin,
sekundarni metabolit bakterije Serratia marcescens, dobijen je gajenjem S.
marcescens u tečnoj podlozi sa homogenizovanim mesnim nareskom, a prinos
prodigiozina je poboljšan čak 10 puta u poređenju sa standardnom podlogom.1
Kada je Pseudomonas sp. BK25H gajen u podlozi sa komponentama kuhinjskog otpada
dobijen je odličan prinos piocijanina od 12,5 mg L-1. Slično, aktinomicin D i
staurosporin, sekundarni metaboliti Streptomyces sp. BV365 i 410, su dobijeni
gajenjem proizvođača u hranjivim podlogama sa komponentama poljoprivrednog
otpada ili otpada dobijenog preradom lignoceluloze. S obzirom da neka od
navedenih jedinjenja dostižu komercijalnu vrednost od 2.500,00 evra za 1 mg
(https://www.sigmaaldrich.com/RS/en/product/sigma/s5921), dobijeni rezultati idu u
prilog ideji da bi se otpadne materije mogle koristiti kao jeftine sirovine za
proizvodnju vrednih hemikalija, uz istovremeno smanjenje njihove cene, pri čemu
bi se i količina otpadnih tokova redukovala.Иако су биотерапеутици довели до револуционарних промена у лечењу рака,
доказали своју ефикасност у санирању микробних инфекција и лечењу људи са
ретким болестима, због високе цене нису свима доступни. Иновативни приступ где
отпад улази у састав храњивих подлога за гајење бактерија би могао довести до
смањења цене биотерапеутика. Ферментацијом на скали од 5 L је добијено
неколико биоактивних природних производа, при чему је различит отпад био извор
храњивих материја за гајење микроорганизама произвођача. Продигиозин,
секундарни метаболит бактерије Serratia marcescens, добијен је гајењем S.
marcescens у течној подлози са хомогенизованим месним нареском, а принос
продигиозина је побољшан чак 10 пута у поређењу са стандардном подлогом.1
Када је Pseudomonas sp. BK25H гајен у подлози са компонентама кухињског отпада
добијен је одличан принос пиоцијанина од 12,5 mg L-1. Слично, актиномицин Д и
стауроспорин, секундарни метаболити Streptomyces sp. BV365 и 410, су добијени
гајењем произвођача у храњивим подлогама са компонентама пољопривредног
отпада или отпада добијеног прерадом лигноцелулозе. С обзиром да нека од
наведених једињења достижу комерцијалну вредност од 2.500,00 евра за 1 mg
(https://www.sigmaaldrich.com/RS/en/product/sigma/s5921), добијени резултати иду у
прилог идеји да би се отпадне материје могле користити као јефтине сировине за
производњу вредних хемикалија, уз истовремено смањење њихове цене, при чему
би се и количина отпадних токова редуковала.Knjiga sažetaka: Treći Kongres biologa Srbije, Zlatibor, Srbija 21 - 25. 9. 2022