imagine (Institute of molecular genetics and genetic engineering)
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MITOCHONDRIAL MYOPATHY CAUSED BY MT-ND5 VARIANT: INTEGRATING WES AND MITOCHONDRIAL DNA ANALYSIS
No full textMitochondrial disorders caused by pathogenic
variants in mitochondrial genome represent a
heterogeneous group of disorders, including
mitochondrial myopathy, Leigh syndrome,
MELAS and others. We report a patient with
mitochondrial myopathy caused by a pathogenic
variant in the MT-ND5 gene. The patient is a male
child born after an uneventful full-term
pregnancy from healthy nonconsanguineous
parents. He presented with failure to thrive with
psychomotor delay and recurrent infections.
Neurologic examination at 11 months revealed
axial hypotonia with limb hypertonia,
hyperreflexia, head tremor, weak supporting and
postural responses, hypomimic face, bilateral
eyelid semiptosis, convergent strabismus and
inability to visually track objects. Elevated serum lactate prompted further metabolic analyses
which indicated a defect in oxidative
phosphorylation. Whole exome sequencing
(WES) analysis aimed at nuclear-encoded
mitochondrial genes was negative, but the
analysis of mitochondrial DNA revealed a
pathogenic variant c.758T>C (p.Val253Ala) in
the MT-ND5 gene, with a heteroplasmy level of
54%. Variant was confirmed by Sanger
sequencing, while the analysis of maternal
sample showed that the variant arose de novo.
This study highlights the importance of
integrating mitochondrial DNA analysis with
WES to enable precise diagnosis and treatment of
different mitochondrial disorders.Book of abstract: 15th Balkan congress of human genetics and 3rd Alpe Adria meeting of human genetics, 9 - 11 October 2025, Rikli Balance Hotel ,Bled, Sloveni
Kratak uvod u farmakoekonomiju
No full textPharmacoeconomics is a branch of health economics that evaluates the costs and benefits of pharmaceutical
interventions in resource-limited healthcare systems. Unlike classical economics, healthcare markets
diverge from assumptions of free competition, making structured economic evaluation essential for
policy and clinical decision-making. Key concepts include opportunity cost, utility, marginal utility, willingness
to pay, and the incremental cost-effectiveness ratio (ICER). Pharmacoeconomic studies categorize
costs into direct medical, direct non-medical, indirect, and intangible, assessed from perspectives such
as patients, providers, insurers, and society at large. Evaluation methods encompass cost-effectiveness,
cost-utility, cost-minimization, cost-benefit, and cost-threshold analyses, each suited to specific decision
contexts. Central to these approaches is the measurement of health outcomes and utilities, often quantified
in Quality-Adjusted Life Years (QALYs) through instruments like EQ-5D or SF-6D. Decision-analytic
frameworks, including decision trees and Markov models, support the projection of long-term outcomes
and uncertainty management in complex disease pathways. Together, these tools guide evidence-based
resource allocation, aiming to balance clinical effectiveness, quality of life, and economic sustainability.
This review provides a concise overview of the principles, methods, and models underpinning pharmacoeconomics,
highlighting its role in optimizing therapeutic choices and informing healthcare policy.Farmakoekonomija predstavlja granu zdravstvene ekonomije koja procenjuje troškove i koristi farmaceutskih
intervencija u uslovima ograničenih resursa zdravstvenog sistema. Za razliku od klasične
ekonomije, tržišta zdravstvene zaštite odstupaju od pretpostavki slobodne konkurencije, što čini sistematsku
ekonomsku evaluaciju neophodnom za oblikovanje politika i donošenje kliničkih odluka. Ključni
pojmovi uključuju oportunitetni trošak, korisnost, graničnu korisnost, spremnost na plaćanje i inkrementalni
odnos trošak-efikasnost (ICER). Farmakoekonomske studije klasifikuju troškove na direktne medicinske,
direktne nemedicinske, indirektne i nematerijalne, posmatrane iz perspektive pacijenata, pružalaca
usluga, fonda zdravstvenog osiguranja i društva u celini. Metode evaluacije obuhvataju analizu troškovne
efektivnosti, troškovne korisnosti, minimizacije troškova, troškova i koristi, kao i pragovnu analizu, pri čemu
je svaka prilagođena specifičnom kontekstu odlučivanja. Centralno mesto u ovim pristupima zauzima
merenje zdravstvenih ishoda i korisnosti, najčešće izraženih kroz godine života prilagođene kvalitetu
(QALY), pomoću instrumenata poput EQ-5D ili SF-6D. Analitički okviri odlučivanja, uključujući stabla
odlučivanja i Markovljeve modele, omogućavaju projekciju dugoročnih ishoda i upravljanje neizvesnošću
u složenim bolestima. Ovi alati usmeravaju alokaciju resursa zasnovanu na dokazima, sa ciljem
uravnoteženja kliničke efikasnosti, kvaliteta života i ekonomske održivosti. Ovaj pregled daje sažet prikaz
principa, metoda i modela farmakoekonomije, naglašavajući njenu ulogu u optimizaciji terapijskog izbora
i kreiranju zdravstvene politike
Comparative RNA-Seq Analysis of Colon Spheroids and Patient-derived Tissues Identifies Non-Canonical Transcript Isoforms of Protein-Coding Genes Implicated in Colon Carcinogenesis
No full textObjectives:This study aimed to identify transcript isoforms of protein-coding genes with potential relevance to the malignant transformation of gut mucosa.Methods:Colon cancer cell lines (HCT116, DLD1, SW620) and immortalized cells derived from healthy gut epithelium (HCEC-1CT) were cultured as spheroids and subjected to RNA sequencing to profile both canonical and non-canonical transcripts. The resulting data were compared with prior bioinformatics study findings that analyzed RNA-seq datasets from 473 patient-derived tumor and 417 non-tumor colon tissue samples.Results:Among 375 transcripts previously reported as significantly dysregulated in colon (39 up-regulated and 336 down-regulated), 32 transcripts displayed expression patterns in colon cell lines consistent with those observed in patient tissues (4 up-regulated and 28 down-regulated). In silico characterization of these molecules revealed that all of them exhibited at least 1 feature commonly associated with RNAs possessing regulatory functions, such as coding truncated protein isoform, exosomal localization, or enrichment in repetitive elements. The most prominently dysregulated transcripts with consistent expression profiles across both datasets were NTMT1-204 (up-regulated in cancer) and BLOC1S6-218 and DCTN1-205 (both down-regulated in cancer). The remaining 343 transcripts did not show consistent expression patterns in the cell lines, suggesting their dysregulation in patient-derived tissues may be due to the stromal or microenvironmental factors absent in vitro.Conclusion:In summary, this comparative transcriptomic analysis identified 32 transcript isoforms, comprising 2 canonical and 30 non-canonical transcripts, that may play regulatory roles in colon carcinogenesis and warrant further investigation in the context of gut epithelial cell biology
Targeting Melanogenesis with Postbiotics: An Integrated Zebrafish-Based Assessment of Lactobacillus salivarius BGHO-1 and Lactobacillus paracasei BGSJ2-8
No full textSkin hyperpigmentation disorders represent a major dermatological challenge, and safe
alternatives to conventional depigmenting agents remain scarce. Probiotics and their postbiotic derivatives have emerged as promising natural candidates; however, only a few
bacterial strains have been investigated for melanogenesis-inhibitory activity, and their
true potential remains largely unexplored. Here, we report for the first time the biosafety
profile and anti-melanogenic activity of Lactobacillus salivarius BGHO-1 and Lactobacillus
paracasei BGSJ2-8, and assess their possible use in the treatment of skin hyperpigmentation. Two complementary zebrafish-based approaches were employed: (i) image-assisted
analysis of pigmentation patterns, melanocyte morphology, and melanocytotoxicity, and
(ii) quantitative melanin analysis, enabling integrated safety and efficacy evaluation. We
investigated both native and heat-inactivated preparations, including whole cultures, cellfree supernatants, isolated cells, and separated cell walls/membranes and cytoplasmic
fractions. While several fractions demonstrated the ability to inhibit melanogenesis, the cell
wall/membrane fraction was the most potent, reducing melanin content by 64% compared
to untreated embryos, while causing no systemic side effects and preserving melanocyte
structure. Furthermore, this fraction did not elicit inflammatory responses or neutropenia, underscoring its favorable safety profile at anti-melanogenic doses. Collectively, this
study identifies specific postbiotics as effective and safe modulators of melanogenesis
and highlights their translational potential in developing novel approaches for treating
skin hyperpigmentatio
Environmental microorganisms and their populations as biotechnological solution to plastic pollution
No full textGlobal research efforts to develop biotechnological solutions for plastic waste management,
based on environmental microbes and their consortia, are underway. Multipronged approach,
combining different strategies such as metagenomics, functional screening, directed evolution
and metabolic engineering of degrading microbes, represents a step forward for achieving a
circular economy for plastics.
Despite a proposed overlap between microbial enzymatic capacity to degrade lignocellulosic
biomass and plastics, bioprospecting efforts to identify microorganisms able to catabolize both
types of substrates remain limited. Studies focusing on environmental niches that are not readily
accessible for sampling, representing underexplored reservoirs of enzymatic activities with
potential biotechnological applications, are also relatively scarce.
Screening of 1000 environmental isolates, from water and soil environments that are not typically
included in bioprospecting efforts and from laboratory evolved natural and synthetic consortia,
for degradation of a range of plastic and lignocellulosic substrates and metataxonomic profiling
of selected screened environments, as well as the assessment of their overall functional potential
and future directions will be presented.VII Congress of the Serbian Genetic Society Zlatibor; October 2 to 5, 2024
IDENTIFICATION OF CELLULAR FACTORS IN USTILAGO MAYDIS INVOLVED IN THE CELL'S RESPONSE TO CYTOTOXIC AND GENOTOXIC STRESS
No full textThroughout their lifespan, microorganisms encounter various environmental changes. Some
changes are beneficial, while others have negative impacts on their survival and reproduction.
To adapt to these negative changes, microorganisms have developed different strategies. We
have discovered that unicellular basidiomycete Ustilago maydis can restore population
abundance after devastating stress by utilizing biomolecules freed from dying cells. We named
this repopulation strategy "Repopulation upon shattering" (RUS). However, utilizing these
nutrient-rich biomolecules is challenging as they also exhibit toxic effects on cells. Therefore,
U. maydis needs to employ a wide variety of cellular factors to utilize these nutrients
successfully. Our research has revealed that some of these factors also play important roles in
genome stability. We have identified 5 cellular factors (RGS6, RGS9, RGS22, RGS24, RGS26)
that are crucial for the mechanisms of RUS and genome integrity. RGS6 refers to nonmuscle
myosin heavy chain IIa, RGS9 is the DNA repair exonuclease REC1, RGS22 is the ubiquitin
specific protease 7, RGS24 is the receptor for activated kinase 1 (RACK1), and RGS26 is the
ubiquitin specific protease 8. Mutations in any of these genes lead to the inability of mutant
cells to recover from oxidative stress and to repair DNA lesions caused by genotoxic agents
such as MMS, DEB, HU, and UV radiation.VII Congress of the Serbian Genetic Society Zlatibor; October 2 to 5, 2024
NT2/D1 EARLY NEURAL PROGENITORS IN 3D ALGINATE MICROFIBERS AS A MODEL SYSTEM FOR SCREENING THE EFFECT OF BIOACTIVE COMPOUNDS
No full textNT2/D1 embryonal carcinoma cells represent a well-established in vitro model of human
neurogenesis. Alginate fibers’ platform, a 3D cell culture system, is a biocompatible,
structurally supportive environment for neurogenesis suitable for investigating the effects of
bioactive compounds on neurodevelopment.
Using manual extrusion NT2/D1 cells were immobilized in alginate microfibers and neural
differentiation was induced by 48h of induction with retinoic acid (RA). Initiation of neural
differentiation in the 3D model was evaluated by assessment of morphological features, cell
viability, apoptosis and expression of pluripotency factors and early neural markers. Using the
same methodology, we investigate potential effects of major components of energy drinks,
caffeine and taurine, on the NT2/D1 early neural progenitors.
We established the alginate microfibers as a 3D model system for in vitro neural differentiation
of immobilized NT2/D1 cells and evaluated the effects of caffeine and taurine on the early
stages of neural differentiation of NT2/D1 cells. Upon RA induction NT2/D1 neural progenitors
retained viability and proliferative capacity and showed decreased expression of pluripotency
markers SOX2, OCT4, and NANOG and increased expression of early neural markers SOX3,
PAX6, and miR219. We also revealed the effects of caffeine and taurine on the viability,
proliferation and expression of SOX2 and PAX6 of the NT2/D1 neural progenitors.
Neural differentiation of NT2/D1 cells immobilized within alginate microfibers represents a
promising 3D model for studying the effects of bioactive compounds on human neurogenesis.VII Congress of the Serbian Genetic Society Zlatibor; October 2 to 5, 2024
PATIENT-DERIVED INDUCED PLURIPOTENT STEM CELLS WITH 22Q11.2 MICRODELETION: A MODEL SYSTEM FOR INVESTIGATING NEURODEVELOPMENTAL DISORDER
No full textNeurodevelopmental disorders (NDDs) like autism spectrum disorders, intellectual disability
and schizophrenia represent considerable public health challenges. Molecular pathways
underlying NDDs remain largely unidentified. Syndrome associated with a heightened risk of
NDDs is 22q11.2 Deletion Syndrome (22q11.2DS), caused by microdeletion 22q11.2. In 98%
of cases the microdeletion is 1.5Mb or 3Mb in length. This study is focused on a cohort of
patients with 1.5Mb microdeletion, aiming to establish model system for investigation of
NDDs.
Peripheral blood mononuclear cells from patients with 1.5 Mb microdeletion and healthy
individuals were reprogrammed using CytoTuneTM-iPS2.0 Sendai Reprogramming Kit.
Generated induced pluripotent stem cells (iPSCs) were genotyped in order to identify if any
additional pathogenic CNVs exist. Pluripotency of the iPSCs was assessed through RT-PCR
analysis. STEMdiff Trilineage Differentiation Kit was used to validate the ability of iPSCs to
differentiate into the cells of three germ layers: ectoderm, mesoderm, and endoderm.
iPSCs were generated from three patients with a 1.5Mb microdeletion and two healthy
individuals. They expressed pluripotency markers and differentiated into cells of three germ
layers. Genotyping identified additional CNVs in some of the iPSC lines.
iPSC lines from 22q11.2DS patients and healthy controls were successfully established and
they provide a valuable platform for studying NDDs.VII Congress of the Serbian Genetic Society Zlatibor; October 2 to 5, 2024
NEW INSIGHTS INTO MOLECULAR COMPLEXITY OF GENOME PROTECTION IN USTILAGO MAYDIS
No full textThe maintenance of genome integrity is one of the most fundamental cellular processes that
ensures genome stability by employing molecular factors that are mostly conserved in all
domains of life. Our research focuses on identification of novel cellular components of the
molecular machineries underlying preservation of genome integrity concentrating our focus on
homologous recombination (HR)-mediated repair of double strand brakes. For this purpose, we
exploit a model system Ustilago maydis. Several facts make this microorganism suitable for
this type of research: it is extremely radiation resistant with HR at the base of this resistance;
30% of its genes are of unknown function which opens possibility that some of these are
dedicated to modulation/regulation of HR and DNA repair; it is a BRCA2 organism showing
some surprising features in common with the higher eukaryotes’ (including humans’) HR
system. Besides, U. maydis possesses an impressive capacity to recover from massive damage
i.e., to reconstitute devastated cell populations by recycling biomolecules released from dead
cells. Importantly, we have found that this substrate may be mutagenic which opens up a
methodological approach to identify new genes involved in both processes-repopulation and
genome protection.
Through different approaches we have identified and partially characterized a number of
cellular factors responsible for maintenance of genome integrity. Two are previously known
HR factors, while majority are completely uncharacterized genes. Notably, we have identified
novel components of HR machinery, as well as components of cytoskeleton, endosomes,
chromatin remodeling complexes, transcription regulation whose absence leads to genome
instability.VII Congress of the Serbian Genetic Society Zlatibor; October 2 to 5, 2024
Transcriptome profiling provides insight into the mechanism of siliconmediated mitigation of copper stress in cucumber plants
No full textCopper (Cu) toxicity significantly impairs optimal plant growth and development. Silicon (Si)
has been recognized for its beneficial effects on plants exposed to stress. While the mechanisms
by which silicon induces stress resistance in plants are diverse, the molecular regulation remains
unclear. To identify the molecular pathways that may enhance copper tolerance in cucumber
plants, we conducted transcriptome analyses of both control and copper-treated cucumber roots,
with and without added Si. Our comparative transcriptome analysis revealed that Si significantly
influenced gene expression in cucumber plants. Under control conditions, Si treatment altered
the expression of 1,841 genes (1,365 up-regulated and 476 down-regulated), which were primarily
involved in response to stimulus, transcription regulator activity, cell wall organization and metabolic
processes. When exposed to copper stress alone, 7,114 genes (4,534 up-regulated and 2,580
down-regulated) exhibited differential expression, with many of these genes related to defense
responses, oxidative stress response, transmembrane transporter activity, and oxidoreductase and
peroxidase activity. Si treatment tended to revert the transcriptome of copper-stressed cucumber
to the level of control plants, altering the expression of a total of 5,375 genes, with 3,601
up-regulated and 1,774 down-regulated. These findings suggest that Si may function as an elicitor,
preconditioning cucumber plants and enhance copper tolerance. This study contributes to our
understanding of the molecular mechanisms underpinning silicon-mediated copper tolerance.Book of abstract: 5th International Conference on Plant Biology (24th SPPS Meeting