imagine (Institute of molecular genetics and genetic engineering)
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Comprehensive pharmacogenomics profiling of the Serbian population
No full textBackground: Pharmacogenomics offers a possibility of anticipating drug response based on individuals’ genetic profiles and represents a step toward implementation of personalized treatment through routine genetic testing. Development of highthroughput sequencing technologies aided identification and interpretation of variants in many pharmacogenes simultaneously. Nonetheless, the integration of pharmacogenomics into clinical practice is arduous, partly due to insufficient knowledge of ethnic pharmacogenetic data. The aim of our study was to assemble the most comprehensive pharmacogenomics landscape of the Serbian population so far.
Methods: We used genomic data of 881 individuals from Serbia obtained by clinical and whole exome sequencing. Raw sequencing files were processed using an in-house pipeline for alignment and variant calling. For annotation of pharmacogenetics star alleles and determination of phenotypes, we used the PharmCAT and Stargazer tools. Star allele and phenotype frequencies were calculated and compared to worldwide and European populations. Population differentiation was presented through calculation of Wright’s fixation index.
Results: Our results showed that population differentiation was the highest between the Serbian and the worldwide population. In the Serbian population, the most relevant pharmacogenes in terms of star allele frequencies and actionable phenotypes were CYP2B6, NAT2, SLCO1B1, UGT1A1 and VKORC1, that had significantly different distribution compared to other European populations.
Conclusion: In conclusion, significant differences in frequencies of pharmacogenetic phenotypes that influence response to several drug categories including statins and antidepressants indicate that inclusion of data relevant for drug response to genetic reports would be beneficial in the Serbian population. Implementation of pharmacogenetic testing could be achieved through analysis of clinical and whole exome sequencing data
Development of κ-Carrageenan/Gelatin pH-Responsive Hydrogels for Potential Skin Regeneration Application
No full textAdvanced skin care involves innovative, multifunctional, and bio-inspired biomaterials capable of regenerating skin tissue. Here, we report the facile route for the fabrication of the bio-sourced pH-responsive hydrogels based on κ-carrageenan and gelatin, with properties desirable for the treatment of versatile skin disorders. The extensive characterization revealed differences in physicochemical properties due to chemical modifications of the hydrogels. Porosity ranged from 21.67% to 95.81%. By modifying κ-carrageenan hydrogels with gelatin, the Young's modulus values increased proportionally with the gelatin content, ranging from 0.23 to 2.90 MPa, while native κ-carrageenan hydrogels had the lowest values (0.12–0.42 MPa) and native gelatin hydrogels had the highest (10.85–18.03 MPa). Native κ-carrageenan hydrogels exhibited the most pronounced swelling (18.6–27.0), followed by gelatin-modified κ-carrageenan hydrogels (6.5–23.0) and native gelatin hydrogels (7.8–9.0). The native κ-carrageenan hydrogels also displayed the highest water vapor transmission rate (WVTR) (259.99 ± 16–279.91 ± 19 g m−2 day−1), while the presence of gelatin lowered it. The hydrogels were preliminary exposed to human fibroblasts (MRC-5 cell line) and then to Caenorhabditis elegans to reveal the effects on whole living organisms. The summarized results suggest that the hydrogels represent advantageous and versatile biocompatible biomaterials set for further investigation as delivery platforms for bioactive molecules suitable for skin tissue regeneration.e70008 BIP-2024-0163.R
AKR1B1 Expression in the Colorectal Tumor Microenvironment Contributes Towards Its Prognostic Significance
No full textBackground AKR1B1, a member of the aldo-keto reductase enzyme family involved in the polyol pathway of aldehyde metabolism, is aberrantly expressed in colorectal cancer (CRC). Our previous studies demonstrated that AKR1B1 knockdown reduced the motility and proliferation of CRC cell lines, and its elevated expression was correlated with increased mesenchymal marker expression, inflammation, and poor prognosis in CRC patient cohorts. However, whether stromal cells also express AKR1B1 and whether stromal expression can affect clinical outcomes has not been examined. Objectives To evaluate the expression of AKR1B1 within the tumor microenvironment (TME) of CRC, with a paticular focus on stromal cells, and to assess its association with clinical outcomes. Methods We assessed AKR1B1 expression in colorectal tumors utilizing publicly available transcriptomic data from CRC tumors. Single-cell RNA-sequencing data from CRC samples were analyzed to determine cell type-specific expression. Immunohistochemistry based assessment of AKR1B1 expression was performed in Turkish and Serbian cohorts. Co-localization of AKR1B1 and CD163 (M2 macrophage marker) was evaluated by immunoflourescence. Results AKR1B1 was expressed in both the epithelial and stromal components of colorectal tumors, with higher expression observed in the stroma. Single-cell transcriptomic analysis revealed AKR1B1 expression in myeloid cells, T and NK cells, B cells, dendritic cells, fibroblasts, and epithelial cells. Notably, AKR1B1-expressing macrophages were predominantly of the M2 phenotype, and AKR1B1 expression and M2 marker expression showed strong positive correlation in bulk transcriptomic data. Immunofluorescence confirmed the colocalization of CD163 and AKR1B1 in stromal macrophages. Moreover, immunohistochemical analysis of AKR1B1 expression in tumor stroma from a cohort of Turkish patients revealed that its expression was associated with favorable overall survival, particularly in tumors with higher stromal infiltration. Conclusions Overall, our findings underscore the significant influence of the TME composition on the relationship between AKR1B1 expression and clinical outcomes.e70974 CAM4-2025-01-0456.R
Strains of the genus Acinetobacter, potential degraders of plastics
No full textThe genus Acinetobacter is a group of diverse Gram-negative saprobic bacteria that are a major cause of nosocomial
infections worldwide. However, this genus also contains many environmentally important species as well, which can
degrade contaminants such as hydrocarbons and crude oil [1]. In the recent years there are studies that report
Acinetobacter strains as degraders of plastic materials, primarly polyethylene. Lyu and co-workers showed that a deepsea
bacterium, Acinetobacter venetianus F1, can biodegrade polyethylene via alkane metabolic pathway [2]. That is
promising solution because excessive production and use of plastic leads to environmental pollution, and it is necessary
to find novel potent strains for improving the remediation techniques [3]. In this work, the potential of strains of the
genus Acinetobacter for the degradation of various plastic substrates was investigated, including: terephthalic acid
(TPA), bis(2-hydroxyethyl) terephthalate, polycaprolactone, impranil, polyethylene terephthalate, polyhydroxybutyrate,
linear low density polyethylene and polypropylene. The study was conducted on plates with mineral agar which
contained 2% each substrate as carbon source. Acinetobacter strains isolated from the polluted environment were
investigated. The results showed that all strains of the genus Acinetobacter, produce enzymes involved in the
degradation of various plastic substrates. The most promising strains are A. proteolyticus and A. haemolyticus which
can grow at all investigated substrates except TPA. With this study, our group has contributed to the discovery of new
strains that can be used in bioremediation processes to reduce plastic pollution, however futher experiments for
optimization of conditions to obtain high degradation percentages for each substrate as well as degradation mechanisms
are needed.E-book: 19th International Conference on Chemistry and the Environment ICCE 2025 Belgrade 8-12 June 202
Phenolicsandcellwallremodellingin fruits of tomatooverexpressing GGP1gene
No full textTomato fruit ripening involves complex physiological processes, including the biosynthesis and degradation of cell wall components such as polysaccharides, phenolics, and proteoglycans, leading to fruit softening. In this study, we investigated how the overexpression of GDP-Lgalactose phosphorylase (GGP1)– a key gene in the Lgalactose-dependent ascorbate (Asc) biosynthesis pathway- under the control of two fruit-specific promoters, namely PPC- phosphoenolpyruvate carboxylase and PG– polygalacturonase, influences cell wall properties and phenolic profile. It was shown that GGP1 overexpression increases Asc content in ripening tomato fruit and upregulates genes associated with cell wall remodelling [1]. Here, we demonstrated that PPC-GGP1 and PG-GGP1 transgenic lines exhibited significant structural alterations in the fruit parenchyma compared to wild-type fruits, particularly a disruption of cell wall composition and organisation [2]. These included modifications in spatial distribution and chemical composition of homogalacturonans and arabinogalactans, as well as changes in the pectin methylation degree. Alongside with reduced content of free chalconaringenin, p-coumaric and protocatechuic acids, the amount of cell wall-bound p-coumaric acid and the corresponding monolignol, p-coumaryl alcohol, was higher in the transgenic fruits. These findings highlight a metabolic interplay between Asc biosynthesis and cell wall remodelling, with potential implications for postharvest fruit quality and storage.Programme and Book of Abstracts 25-28 JUNE 2025, Budapes
Transcript PHF19-207 May Be a Long Non-Coding RNA with Tumor-Promoting Role in Colon Cancer
No full textRecent pan-cancer transcriptome analysis has revealed differential activity of two alternative PHF19 gene promoters in malignant versus non-malignant gut mucosa. One of these promoters upregulated in colon cancer leads to the expression of the PHF19-207 transcript, suggesting its potential role in tumor promotion. The objective of this study was to investigate the function of PHF19-207 using in silico tools and publicly available data, as well as to assess its expression in colon cancer. Expression analyses were conducted via qPCR and RNA sequencing on RNA extracted from the immortalized colonic epithelial cell line HCEC-1CT, as well as a series of colon cancer cell lines cultured in both 2D and 3D environments. The expression of PHF19-207 was found to be elevated in all malignant cell lines compared to the non-malignant HCEC-1CT cell line in both culture conditions, with the most prominent increase observed in cell lines derived from advanced stages of the disease and in the HCEC-1CT cell line overexpressing KRAS. Furthermore, the PHF19-207 transcript was detected in exosomes derived from malignant cells. These findings suggest that PHF19-207 holds potential as a diagnostic biomarker. In addition, in silico analyses indicate that this transcript may function as a long non-coding RNA involved in the regulation of gene expression. Further functional investigations are required to elucidate its precise role in colon carcinogenesis
The role of the Notch signaling pathway in rhabdomyosarcomas
No full textRhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with poor prognosis in cases of metastasis. Different
signal transduction pathways have been studied in RMS cells as to shed some light into the tumorigenesis and metastasis
mechanisms of this cancer in the search for new diagnostic and therapeutic strategies. The Notch pathway,
which regulates cell survival, is widely studied in different cancers, including sarcomas and its activation has been
known to induce cell motility. To this end, the present review explores the role of the Notch signaling pathway in the
progression of RMS and in potential therapeutic strategies
Mechanisms Maintaining Mitochondrial DNA Polymorphisms: The Role of Mito-Nuclear Interactions, Sex-Specific Selection, and Genotype-by-Environment Interactions in Drosophila subobscura
No full textExperimental mito-nuclear introgression lines (MNILs) were established by backcrossing isofemale lines of D. subobscura originating from the same populations. MNILs were subjected to a series of life-history experiments designed to test the fitness of the bearers of different combinations of two main mtDNA haplotypes on their own nuclear background, as well as on the background of the opposite haplotype. By having 11 replicas of the four mito-nuclear combinations, we could test not only the adaptive significance of the differences between the two main haplotypes but also the influence of additional variation present within each of the 11 combinations on fitness. Testing the fitness of individuals of both sexes enabled us to examine if sex-specific selection has a role in maintaining the frequencies of the two mtDNA haplotypes in nature. Conducting the fitness assays on two different temperatures enabled us to test whether different temperatures favor specific mtDNA haplotypes or mito-nuclear genotypes and consequently promote stable sympatric mtDNA variation. The results show weak signature of genotype-by-environment interactions, and no sex-specific selection regarding differences between the two main haplotypes. However, individual models across different life-history components showed these two mechanisms at play in promoting mtDNA variability present in specific mito-nuclear crosses. Our models show that mito-nuclear interactions are, in fact, more important as units of selection
Lung Microbiota: From Healthy Lungs to Development of Chronic Obstructive Pulmonary Disease
No full textDie Gesundheit der Lunge hängt von einem komplexen Zusammenspiel der Lungenmikrobiota ab. Diese setzt sich aus der Bakteriota, der Mykobiota und dem Virom zusammen. Studien haben gezeigt, dass die Lungenmikrobiota eine entscheidende Rolle beim Schutz des Wirtsorganismus spielt, indem sie die angeborene und adaptive Immunität der Lunge reguliert. Bei der chronisch-obstruktiven Lungenerkrankung (COPD) handelt es sich um eine entzündliche Erkrankung der Lunge, die durch eine veränderte Zusammensetzung und Vielfalt der Mikrobiota (Dysbiose) gekennzeichnet ist. Die Lungendysbiose nimmt mit dem Fortschreiten der COPD und während Exazerbationen zu. Es wurden 2 Modelle der Dysbiose vorgeschlagen: Dysbiose- und Entzündungszyklen sowie die Störung des bakteriellen Interaktoms. Ob der treibende Faktor für die Pathogenese der COPD jedoch beim Wirt oder bei der Mikrobiota liegt, ist noch unbekannt. Zwar wurden in jüngster Zeit die Wechselwirkungen zwischen Wirt und Mikrobiota sowie zwischen den Mikroben untereinander bei COPD hervorgehoben, doch die zugrunde liegenden Mechanismen müssen noch weiter erforscht werden. Die Funktion der Darm-Lungen-Achse ist für die Aufrechterhaltung der Lungengesundheit von entscheidender Bedeutung. Bei COPD ist diese Funktion jedoch beeinträchtigt. Die Anwendung von Probiotika hat sich als vorteilhaft für den Wirt erwiesen und es ist wahrscheinlich, dass zukünftige Fortschritte in diesem Bereich zur Therapie von COPD beitragen werden. In dieser Übersichtsarbeit werden die Zusammensetzung der Lungenmikrobiota, molekulare Mechanismen sowie klinische Aspekte im Hinblick auf Wirt und Mikrobiota bei Gesundheit und COPD umfassend dargestellt.Lung health is dependent on a complex picture of the lung microbiota composed of bacteriobiota, mycobiota, and virome. The studies have demonstrated that the lung microbiota has a crucial role in host protection by regulating innate and adaptive lung immunity. Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease featuring changed microbiota composition and diversity, known as a dysbiosis. The lung dysbiosis increases with the progress of COPD and during exacerbation. Two models of dysbiosis have been proposed: dysbiosis and inflammation cycles and the disturbance of bacterial interactome. Still, it is unknown if the driving factor of the pathogenesis of COPD belongs to the host or microbiota. Recently, host–microbiota and microbe–microbe interactions have been highlighted in COPD, but the mechanisms behind these interactions need further exploration. The function of the gut–lung axis is crucial for the maintenance of lung health and is affected in COPD. The application of probiotics has resulted in host–beneficial effects, and it is likely that future progress in this field will aid in the therapy of COPD. In this review, the composition of the lung microbiota, molecular mechanisms, and clinical aspects relating to host and microbiota in health and COPD are comprehensively provided.This is translated version of original paper: Stanković, M.. (2025). Lung Microbiota: From Healthy Lungs to Development of Chronic Obstructive Pulmonary Disease. in International Journal of Molecular Sciences MDPI., 26(4), 1403. [https://doi.org/10.3390/ijms26041403
Supplementary information for the article:Parezanovic, M., Stevanovic, N., Andjelkovic, M., Ugrin, M., Pavlovic, S., Stojiljkovic, M., & Skakic, A. (2025). Phenylbutyric Acid Modulates Apoptosis and ER Stress-Related Gene Expression in Glycogen Storage Disease Type Ib In Vitro Model. Molecular Genetics & Genomic Medicine, 13(1), e70054. https://doi.org/10.1002/mgg3.70054
No full textTable 1. Guide RNA sequences (gRNAs) used for CRISPR/Cas9-knockout, Table 2. Primers used for PCR amplification, Table 3. Primers used for RT-qPCR methodRelated to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/2762]Supplementary material for: [https://doi.org/10.1002/mgg3.70054