imagine (Institute of molecular genetics and genetic engineering)
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DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases
Get PDFThere has always been a tendency of medicine to take an individualised approach to treating patients, but the most significant advances were achieved through the methods of molecular biology, where the nucleic acids are in the limelight. Decades of research of molecular biology resulted in setting medicine on a completely new platform. The most significant current research is related to the possibilities that DNA and RNA analyses can offer in terms of more precise diagnostics and more subtle stratification of patients in order to identify patients for specific therapy treatments. Additionally, principles of structure and functioning of nucleic acids have become a motive for creating entirely new therapy strategies and an innovative generation of drugs. All this also applies to cardiovascular diseases (CVDs) which are the leading cause of mortality in developed countries. This review considers the most up-to-date achievements related to the use of translatory potential of DNA and RNA in treatment of cardiovascular diseases, and considers the challenges and prospects in this field. The foundations which allow the use of translatory potential are also presented. The first part of this review focuses on the potential of the DNA variants which impact conventional therapies and on the DNA variants which are starting points for designing new pharmacotherapeutics. The second part of this review considers the translatory potential of non-coding RNA molecules which can be used to formulate new generations of therapeutics for CVDs
Comparative genomics and molecular epidemiology of colistin-resistant Acinetobacter baumannii
Get PDFThis study aimed to investigate the prevalence and resistance mechanisms of colistin-resistant Acinetobacter baumannii (ColRAB) isolates in Serbia, assess their genetic relatedness to other circulating A. baumannii isolates in the neighbouring European countries, and analyse the global genomic epidemiology of ColRAB isolates. A total of 784 isolates of A. baumannii were recovered from hospitalised patients in Serbia between 2018 and 2021. The antimicrobial susceptibility testing was performed using disk diffusion and broth microdilution. All ColRAB isolates were subjected to DNA isolation and whole-genome sequencing (WGS). Overall, 3.94 % (n = 30) isolates were confirmed as ColRAB. Results of mutational and transcriptional analysis of genes associated with colistin resistance indicate the central role of the two-component regulating system, PmrAB, and increased expression of the pmrC gene in ColRAB. Most of the isolates (n = 29, 96.6 %) belonged to international clone II, with the most common sequence type being STPas2 (n = 23, 76.6 %). Based on the WGS analysis, ColRAB isolates belonging to the same ST isolated in various countries were grouped into the same clusters, indicating the global dissemination of several high-risk clonal lineages. Phylogenomic analysis of ColRAB isolates, together with all previously published A. baumannii genomes from South-Eastern European countries, showed that colistin resistance arose independently in several clonal lineages. Comparative genomic analysis revealed multiple genes with various roles (transcriptional regulation, transmembrane transport, outer membrane assembly, etc.), which might be associated with colistin resistance in A. baumannii. The obtained findings serve as the basis for further studies, contributing to a better understanding of colistin resistance mechanisms in A. baumannii.Related to Supplemetary materials: [https://imagine.imgge.bg.ac.rs/handle/123456789/1785]Supplementary data associated with this article can be found in the online version at doi:[10.1016/j.csbj.2022.12.045.
Structural, optical, and bioimaging characterization of carbon quantum dots solvothermally synthesized from o-phenylenediamine
Get PDFCarbon quantum dots as a novel type of carbon nanomaterials have attracted the attention of many researchers because of their
unique optical, antibacterial, and anticancer properties as well as their biocompatibility. In this study, for the first time, carbon
quantum dots were prepared from o-phenylenediamine dissolved in toluene by a solvothermal route. Subsequently, the prepared
carbon quantum dots were encapsulated into polyurethane films by a swelling–encapsulation–shrink method. Analyses of the
results obtained by different characterization methods (AFM, TEM, EDS, FTIR, photoluminescence, and EPR) indicate the significant influence of the precursor on structural, chemical, and optical properties. Antibacterial and cytotoxicity tests showed that these
dots did not have any antibacterial potential, because of the low extent of reactive oxygen species production, and showed low dark
cytotoxicity. By investigating the cellular uptake, it was established that these dots penetrated the HeLa cells and could be used as
probes for bioimaging.Supplementary data: [https://imagine.imgge.bg.ac.rs/handle/123456789/1894
Covid-19 disease severity associated with vitamin d related genetic Variants
Get PDFCOVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The
emerging amount of data indicates that vitamin D could be important for clinical presentation of
COVID-19. Here, we investigated association of genetic variants related to the altered level and
bioavailability of vitamin D with clinical severity of COVID-19. We analyzed variants in genes
significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, and CYP2R1
rs10741657), and vitamin D effect (VDR rs2228570) in 120 Serbian adult and pediatric COVID-19
patients using allelic discrimination. Furthermore, we carried out comparative population genetic
analysis among European and other worldwide populations to investigate variation in allelic
frequencies of selected variants. The results showed that DHCR7/NADSYN rs12785878 and CYP2R1
rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017,
respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the
odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There
were no associations between selected genetic variants and disease severity in pediatric patients.
Comparative population genetic analysis revealed that Serbian population had the lowest frequency of
CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and
0.66 in Spanish and Italian population, respectively), suggesting that other populations should also
investigate the relationship of CYP2R1 variant and the COVID-19 disease course. The results of the
study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults.
This could direct prevention strategies based on population specific nutrigenetic profiles.Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina - ABMBBIH May, 202
Cell Response on Laser-Patterned Ti/Zr/Ti and Ti/Cu/Ti Multilayer Systems
Get PDFArranged patterns obtained via ultrafast laser processing on the surface of Ti/Cu/Ti/Si and Ti/Zr/Ti/Si thin-film systems are reported. Two differently designed multilayer thin films Ti/Cu/Ti/Si and Ti/Zr/Ti/Si were deposited on silicon using the ion sputtering method. The bioactive surfaces of these systems involve the formation of laser-induced periodic surface structures (LIPSS) in each of the laser-written lines of mesh patterns on 5 × 5 mm areas. The formation of nano- and micro-patterns with an ultra-thin oxide film on the surfaces was used to observe the effects of morphology and proliferation of the MRC-5 cell culture line. To determine whether Ti-based thin films have a toxic effect on living cells, an MTT assay was performed. The relative cytotoxic effect, as a percentage of surviving cells, showed that there was no difference in cell number between the Ti-based thin films and the control cells. There was also no difference in the viability of the MRC-5 cells, except for the Ti/Cu/Ti/Si system, where there was a slight 10% decrease in cell viability
Coping with setbacks as early career professionals: transforming negatives into positives
No full textExploring PhaZ depolymerase sequence space for the bio-cyclable loop for biopolymers
Get PDFPolyhydroxyalkanoates (PHA) are a green substitute for conventional plastics,
owing to their biological origin, biodegradability, biocompatibility and structural
diversity. However, environmental biodegradation of PHA is achieved in a time
frame of several months to several years, depending on environmental conditions,
and properties of both PHA and PHA degrading enzymes (PhaZ) [1]. Taking into
account the high production cost of PHA, landfilling at the end of life is not likely to
be cost-effective, so enzymatic biodegradation as an alternative offers an ecofriendly
bio-cyclable route to cost-effective PHA. Our study aims to tailor PhaZ
properties to create suitable biocatalysts for the industrially relevant time frame and
operating conditions. In order to do so, we decided to randomize PhaZ sequences
and functionally screen enzyme variants for accelerated PHA degradation and
improved biocatalyst stability. Up to this day, various phaZ genes have been mutated
solely for mechanistic purposes eg. Catalytic residue identification, and elucidation
of the substrate recognition process [2,3,4,5,6,7].KNJIGA IZVODA: 9. simpozijum Hemija i zaštita životne sredine Kladovo, 4-7. jun 2023. BOOK OF ABSTRACTS : 9th Symposium Chemistry and Environmental Protection Kladovo, 4-7th June 202
Antitumor activity of natural pigment violacein against osteosarcoma and rhabdomyosarcoma cell lines
No full textSarcomas are rare and heterogenic tumors with unclear etiology. They develop in bone and connective tissue, mainly in pediatric patients. To increase efficacy of current therapeutic options, natural products showing selective toxicity to tumor cells are extensively investigated. Here, we evaluated antitumor activity of bacterial pigment violacein in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines.Related to accepted version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1928]Supp. material: [https://imagine.imgge.bg.ac.rs/handle/123456789/1929
A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia
Get PDFAntithrombin resistance is a rare subtype of hereditary thrombophilia caused by prothrombin gene variants, leading to thrombotic disorders. Recently, the Prothrombin Belgrade variant has been reported as a specific variant that leads to antithrombin resistance in two Serbian families with thrombosis. However, due to clinical data scarcity and the inapplicability of traditional genome-wide association studies (GWAS), a broader perspective on molecular and phenotypic mechanisms associated with the Prothrombin Belgrade variant is yet to be uncovered. Here, we propose an integrative framework to address the lack of genomic samples and support the genomic signal from the full genome sequences of five heterozygous subjects by integrating it with subjects’ phenotypes and the genes’ molecular interactions. Our goal is to identify candidate thrombophilia-related genes for which our subjects possess germline variants by focusing on the resulting gene clusters of our integrative framework. We applied a Non-negative Matrix Tri-Factorization-based method to simultaneously integrate different data sources, taking into account the observed phenotypes. In other words, our data-integration framework reveals gene clusters involved with this rare disease by fusing different datasets. Our results are in concordance with the current literature about antithrombin resistance. We also found candidate disease-related genes that need to be further investigated. CD320, RTEL1, UCP2, APOA5 and PROZ participate in healthy-specific or disease-specific subnetworks involving thrombophilia-annotated genes and are related to general thrombophilia mechanisms according to the literature. Moreover, the ADRA2A and TBXA2R subnetworks analysis suggested that their variants may have a protective effect due to their connection with decreased platelet activation. The results show that our method can give insights into antithrombin resistance even if a small amount of genetic data is available. Our framework is also customizable, meaning that it applies to any other rare disease
Revalorization of biodegradable polymers to valuable bacterial nanocellulose
Get PDFLarge amounts of polymers are discarded worldwide each year, leading to a significant
polymer waste in natural environment. The upcycling has been found as an efficient way to
transform polymer waste into high-value biomaterials meeting the conditions required for
circularity by being indefinitely recyclable, without reduction in value or usability.
The presented study refers to the upcycling of commercial biopolymers into bacterial
nanocellulose. Polymer blends, consisted of biodegradable polymers, such as poly(lactic acid),
PLA, poly(butylene succinate), PBS, and poly(ε-caprolactone), PCL. Polymers were hydrolyzed
and the obtained hydrolysates were investigated as potential carbon source for
K. medellinensis ID13488 growth and nanocellulose production. Degradation products were
analyzed using HPLC analysis. Different growth media, including tap water, HS medium,
absence / presence of glucose, were tested and bacterial nanocellulose growth was
confirmed under the most of the tested conditions. Once the BNC growth was set up, the BNC
production was scaled up and the obtained material was investigated in terms of structure
confirmation (FTIR analysis), thermal properties (DSC/TG analysis), morphology (optical
microscopy, AFM analysis) and crystallinity (XRD analysis). Finally, the full life cycle of mixed
biopolymers: from biodegradation to revalorization of end products into bacterial
nanocellulose appeared as perfect model approach to plastic circularity.Biotechnology for a circular bioeconomy: 28 -29 march 2023. AFOB-EFB Virtual conferenc