Factors influencing axillary bud induction on nodal segments of Micromeria pulegium (Rochel) Benth.

Micromeria pulegium (Rochel) Benth.is an endemic species from family Lamiaceae. Plants from this family are characterized by presence of secondary metabolites and antioxidant components. M. pulegium contains pulegone which is a potential bio-insecticide and a bio-pesticide. Natural populations of this species are so small that there is a need for an alternative way of propagate and proliferation of individuals. Method of micropropagation was used with the goal of mass production of plants with the chemical composition of essential oils as similar as possible to that in wild-harvested plants. This paper presents the study on influence of concentration of mineral salts, carbon sources (sucrose and maltose) and nitrogen source (casein hydrolysate) on process of in vitro regeneration of plants through induction of axillary buds on the nodal segments of Micromeria pulegium. The greatest number of axillary buds was formed in explants grown on MS culture medium with 3 % sucrose and 500 mg/L casein hydrolysate

Фотодиелектрична карактеризација светлосног погона Au/TiO2 наномотори у течном медију

This article reports on photodielectric properties of hydrocolloids of TiO2 particles and Au/TiO2 hybrid particles of lateral dimension of ∼200 nm. Illumination of the colloids with visible light did not cause measurable changes in their electrical conductivity, while the application of UV (365 nm) light led to photoinduced increase in conductivity of up to 2%. The photogeneration of ions in water, regardless of the presence of the particles, makes a dominant contribution to the photoinduced increase in conductivity of the colloid

Next generation sequencing as a tool for pharmacogenomic profiling: Nine novel potential genetic markers for targeted therapy in childhood acute lymphoblastic leukemia

Uvod/Cilj Sekvenciranje nove generacije (SNG) omogućilo je genomsko profilisanje svakog bolesnika. Nova saznanja u oblasti farmakogenomike omogućavaju primenu podataka dobijenih ovom metodom u cilju otkrivanja novih mogućih genetičkih markera za ciljanu terapiju mnogih, posebno malignih bolesti. Cilj ovog istraživanja je bio da se primenom SNG odre- di genetski profil akutne limfoblastne leukemije (ALL) kod dece u cilju procene mogućih molekularnih meta za ciljanu terapiju. Metode Analizirali smo DNK uzorke 17 bolesnika obolelih od ALL dečjeg doba koristeći ciljano SNG. Napredne bioinformatičke metode su korišćene da identifikuju nove mutacije u analiziranim genima i da predvide njihov uticaj i farmakogenomski potencijal. Rezultati Identifikovali smo devet genskih varijanti koje do sada nisu opisane u relevantnim bazama podataka. U navedenim varijantama identifikovane su dve 'besmislene' varijante, ABL1 p.Q252* i AKT1 p.W22*, jedna varijanta koja pomera okvir čitanja, STK11 p.G257fs*28, i šest nesinonimnih varijanti. Kreirali smo trodimenzionalni model za četiri proteina koji bi bili produkt novih nesinonimnih varijanti. Analizirali smo farmakogenomski potencijal svake varijante i otkrili da su dve, STK11 c.1023G gt T/ p.L341F i ERBB2 c.2341C gt T/ p.R781W, mogući kandidati za ciljanu terapiju. Zaključak Nove varijante otkrivene u ovoj studiji pripa- daju uglavnom genima povezanim sa Ras signalnim putem, koji je često zahvaćen mutacijama u ALL kod dece. Farmakogenomsko profilisanje svake dečje ALL biće nezamenljivo za nove terapijske pristupe. Detekcija i inicijalna analiza novih genskih varijanti, koja je predstavljena u ovoj studiji, postaće standardna procedura za dizajniranje i razvoj individualizovane terapije za decu obolelu od ALL.Introduction/Objective Next generation sequencing (NGS) technology has enabled genomic profiling of each patient. Growing knowledge in pharmacogenomics makes it possible to use NGS data for discovery of novel potential genetic markers for targeted therapy of many diseases, especially cancers. The aim of this study was to use targeted NGS to make a genetic profile of childhood acute lymphoblastic leukemia (cALL) in order to evaluate potential molecular targets for targeted therapy. Methods We analyzed DNA samples from 17 cALL patients using NGS targeted sequencing. Advanced bioinformatic analysis was used to identify novel mutations in analyzed genes and to predict their effect and pharmacogenomic potential. Results We identified nine variants that have not been previously reported in relevant databases, including two stop-gain variants, ABL1 p.Q252* and AKT1 p.W22*, one frameshift, STK11 p.G257fs*28, and six missense variants. We created three-dimensional models of four proteins harboring novel missense variants. We analyzed pharmacogenomic potential of each variant and found that two of them, STK11 c.1023G gt T/ p.L341F and ERBB2 c.2341C gt T/ p.R781W, are suitable candidates for targeted therapy. Conclusion Most new variants detected in this study were found in the genes associated with Ras signaling pathway, which is frequently mutated in cALL patients. Pharmacogenomic profiling of each cALL will be indispensable for novel therapy approaches. Detection and initial analysis of novel variants, presented in this study, will become a standard procedure for the design and development of individualized therapies for children with ALL, leading to improved patient outcomes

Anthocyanin-functionalized biopolymer films as pH-sensitive indicators

Anthocyanins are water-soluble, non-toxic flavonoid pigments, which produce the blue, red and purple color of many plants. Color change of anthocyanin extracts is a direct consequence of the transformation of their chemical structure when exposed to different pH conditions. Optical properties investigated in UV-Vis absorption and PL spectra show a clear difference between anthocyanins in acidic and in alkaline environments. Chitosan, a natural-based, non-toxic and biodegradable polysaccharide, is chosen as an ideal matrix for nanocomposites. It is proven to be a good carrier for anthocyanins, because of its ability to entrap the indicator dyes and at the same time the ability to release anthocyanins when in contact with an acidic environment. In this research, we have developed anthocyanin-enhanced biopolymer indicator systems, which provide fast colorimetric response to alterations in pH levels of the environment. Transmittance spectra of nanocomposites show excellent light-blocking properties of the films. This opens up possibilities for advancement in future technology of smart biodegradable food packaging biomaterials. The availability of innovative and healthy materials reduces the need for using synthetic plastic in the modern food industry.IX International School and Conference on Photonics : PHOTONICA2023 : book of abstracts; August 28 - September 1, 2023; Belgrad

Gold-riboflavin hybrid nanostrucutures as possible photodynamic therapy agents

This study reports on the optical properties of hybrid nanostructures that comprise gold nanoparticles (Au NPs) and biomolecule riboflavin (vitamin B2, Rb). The riboflavin is photosensitizing molecule and the generation of reactive oxygen species (ROS) by the hybrid nanoparticles was tested in various aqueous and biological environments. It was shown that the gold nanoparticles enhanced the photosensitizing activity of riboflavin. A comparison of EPR spectra obtained for the Au nanoparticle colloid, hybrid nanoparticle colloid and molecular water solution revealed that the strongest ROS signal came from the AuRb nanosystem. Furthermore, the ROS signal stability was much higher than that of the molecular solution, with a time span of several minutes. Photodynamic activity of the AuRb hybrids was tested by using gram-negative bacterium Escherichia coli as a model system. The bacteria were incubated by AuRb nanoparticles and the survival rate of the colonies was investigated by fluorescent bioimaging. The obtain results provide new insights on photosensitizer’s activities and suggest advantages of using metal-based nanoplatforms for developing of novel agents for photodynamic therapies.XVI Photonics Workshop : Book of abstracts; March 12-15, 2023; Kopaonik, Serbi

Importance of genotyping of Thiopurine S-methyltransferase in children with acute lymphoblastic leukaemia during maintenance therapy

Uvod. Tiopurin-S-metiltransferaza (TPMT ) je enzim koji katalizuje inaktivaciju merkaptopurina, leka koji se široko primenjuje u lečenju akutne limfoblastne leukemije (ALL) kod dece. Kada se osobe s nedostatkom TPMT leče standardnim dozama merkaptopurina, kod njih se razvija teška i po život opasna mijelotoksičnost. Cilj rada. Cilj rada je bio da se utvrdi da li kod dece s ALL koji su nosioci mutacije u genu za TPMT individualizovanjem doziranja merkaptopurina može da se smanji mijelotoksičnost terapije, te da li broj tandemskih ponovaka (engl. variable number of tandem repeats - VNTR) u promotoru gena za TPMT ima uticaja na efekte terapije merkaptopurinom. Metod rada Metodima lančane reakcije umnožavanja DNK (engl. polymerase chain reaction - PCR) ispitano je 50 nasumično odabrane dece lečene ALL IC-BFM 2002 protokolom na najčešće mutacije u genu za TPMT. Za 20 dece je PCR metodima određen VNTR genotip. Ispitanicima je tokom faze održavanja beležen broj nedelja kada su terapiju dobijali u punim ili smanjenim dozama, kao i broj nedelja bez terapije. Rezultati Među 50 dece bilo je 29 dečaka (58%) i 21 (42%) devojčica, uzrasta od 1,8 do 17,3 godine (medijana 6,2 godine). Utvrđeno je četvoro (8%) heterozigotnih nosilaca mutacija, kod kojih je otkrivena TPMT*3A varijanta. Posle 12, 14, 16 i 19 nedelja lečenja smanjenim dozama merkaptopurina bolesnici su, zbog dobrog podnošenja terapije, postepeno počeli da primaju punu dozu leka. Nije bilo odlaganja terapije. Smanjenje kumulativne doze merkaptopurina za bolesnike sa TPMT mutacijama bilo je 7,8%, 7,4%, 11,2% i 16,6%. Između dece bez TPMT mutacija i heterozigota nije za- beležena statistički značajna razlika u trajanju lečenja punim (53,6 nasuprot 55,7 nedelja) i smanjenim dozama merkaptopurina (19,9 nasuprot 15,2 nedelje). Otkrivenih VNTR bilo je između četiri i sedam. Većina bolesnika imala je različit broj VNTR na homolognim hromozomima. Najčešće uočen polimorfizam bio je VNTR*5. Nije zabeležena korelacija između nasleđivanja TPMT i VNTR genotipa. Zaključak Farmakogenetskim principima u lečenju ALL dece može se postići napredak u podnošenju lečenja merkaptopurinom.INTRODUCTION Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyses the inactivation of mercaptopurine (MP) which is widely used in the treatment of acute lymphoblastic leukaemia (ALL) of childhood. Potentially fatal myelotoxicity may develop after standard doses of MP in TPMT deficient patients. OBJECTIVES To establish if individually tailored doses of MP can reduce myelotoxicity in ALL patients carrying mutations in the TPMT gene. To establish if variable number of tandem repeats (VNTR) genotype influences the treatment effects of MP. METHOD Fifty randomly selected patients treated according to ALL IC-BFM 2002 protocol were tested for most frequent TPMT gene mutations using PCR based methods. VNTR genotype was determined in 20 children by PCR methods. During the maintenance phase, we recorded the number of weeks when therapy was applied in either full doses, reduced doses or when patients were without any therapy. RESULTS Fifty children were examined, 29 boys (58%) and 21 girls (42%); age ranged from 1.8-17.3 years (median 6.2 years). Four patients (8%) were heterozygous for TPMT mutations, all of them carrying the TPMT*3A variant. After 12, 14, 16 and 19 weeks of therapy with reduced doses of MP, the patients switched to full doses due to good tolerance. There was no therapy omission. Cumulative dose of MP was reduced for 7.8%, 7.4%, 11.2% and 16.6%, respectively, in patients with TPMT mutations. No significant difference was found between children with no mutations and TPMT heterozygotes regarding full dose therapy (53.6 vs. 55.7 weeks, respectively) and reduced dose therapy (19.9 vs. 15.2 weeks respectively). The number of detected VNTRs ranged from four to seven. The majority of patients had different number of VNTRs on homologous chromosomes. Most frequently detected polymorphism was VNTR*5. No correlation was found between TPMT and VNTR genotype inheritance. CONCLUSION Obeying pharmacogenetic principles in the treatment of childhood ALL may improve the tolerance of therapy with MP

Comparative Analysis of Different Methods for Graphene Nanoribbon Synthesis

Graphene nanoribbons (GNRs) are thin strips of graphene that have captured the interest of scientists due to their unique structure and promising applications in electronics. This paper presents the results of a comparative analysis of morphological properties of graphene nanoribbons synthesized by different methods. Various methods have been reported for graphene nanoribons synthesis. Lithography methods usually include electron-beam (e-beam) lithography, atomic force microscopy (AFM) lithography, and scanning tunnelling microscopy (STM) lithography. Sonochemical and chemical methods exist as well, namely chemical vapour deposition (CVD) and anisotropic etching. Graphene nanoribbons can also be fabricated from unzipping carbon nanotubes (CNTs). We propose a new highly efficient method for graphene nanoribbons production by gamma irradiation of graphene dispersed in cyclopentanone (CPO). Surface morphology of graphene nanoribbons was visualized with atomic force and transmission electron microscopy. It was determined that dimensions of graphene nanoribbons are inversely proportional to applied gamma irradiation dose. It was established that the narrowest nanoribbons were 10-20 nm wide and 1 nm high with regular and smooth edges. In comparison to other synthesis methods, dimensions of graphene nanoribbons synthesized by gamma irradiation are slightly larger, but the yield of nanoribbons is much higher. Fourier transform infrared spectroscopy was used for structural analysis of graphene nanoribbons. Results of photoluminescence spectroscopy revealed for the first time that synthesized nanoribbons showed photoluminescence in the blue region of visible light in contrast to graphene nanoribbons synthesized by other methods. Based on disclosed facts, we believe that our synthesis method has good prospects for potential future mass production of graphene nanoribbons with uniform size, as well as for future investigations of carbon nanomaterials for applications in optoelectronics and biological labeling

Half-sandwich ruthenium(II)-arene complexes: synthesis, spectroscopic studies, biological properties, and molecular modeling

In search for antitumor metal-based drugs that would mitigate the severe side-effects of cisplatin, Ru(II) complexes are gaining increasing recent interest. In this work, we report on the synthesis, characterization (1H- and 13C-NMR, FT-IR), and cytotoxicity studies of two new half-sandwich organometallic Ru(II) complexes of the general formula [Ru(η6-arene)(XY)Cl](PF6) where arene = benzene or toluene and XY = bidentates: dipyrido[3,2-a:2′,3′-c]phenazine (dppz) or 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip), which are bound to Ru(II) via two phenanthroline-N atoms in a characteristic “piano-stool” configuration of Ru(II)-arene complexes—as confirmed by vibrational and NMR spectra. In addition, cytotoxic studies were performed for similar half-sandwich organometallic [Ru(η6-p-cymene)(Me2dppz)Cl]PF6 complex (Me2dppz = 11,12-dimethyl-dipyrido[3,2-a:2′,3′-c]phenazine). This study is complemented with elaborate modeling with density functional theory (DFT) calculations, which provided insight into reactive sites of Ru(II) structures, further detailed by molecular docking on the B-DNA dodecamer, which identified binding sites and affinities: most pronounced for the [Ru(η6-benzene)(aip)Cl](PF6) in both A-T and G-C regions of the DNA minor groove. Cytotoxic activity was probed versus tumor cell lines B16, C6, and U251 (B16 mouse melanoma, C6 rat glioma, U251 human glioblastoma) and non-tumor cell line HACAT (HACAT normal human keratinocytes).This is the peer-reviewed version of the following article:Nikolić, S.; Grgurić-Šipka, S.; Djordjević, I. S.; Dahmani, R.; Dekanski, D.; Vidičević, S.; Tošić, J.; Mitić, D.; Grubišić, S. Half-Sandwich Ruthenium(II)-Arene Complexes: Synthesis, Spectroscopic Studies, Biological Properties, and Molecular Modeling. Journal of Coordination Chemistry 2019, 72 (1), 148–163. [https://doi.org/10.1080/00958972.2018.1553298].Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3753

Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia

Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context