imagine (Institute of molecular genetics and genetic engineering)
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Ispitivanje uticaja simultane inhibicije PAR1 i PAR2 receptora na tumorigene osobine ćelija kolorektalnog karcinoma
No full textNa osnovu podataka internacionalne agencije za istraživanje raka i njihove internet baze
podataka o globalnoj statistici u vezi pojave raka (eng. Global Cancer Statistics,
GLOBOCAN), procenjuje se da se u 2020. u svetu pojavilo 19.3 miliona slučajeva
novoobolelih od malignih tumora (18,1 milion novoobolelih ako izuzmemo nemelanomski
karcinom kože) i skoro 10 miliona preminulih (9.9 miliona ako izuzmemo nemelanomski
karcinom kože). Poslednjih godina karcinom dojke je prestigao karcinom pluća po
učestalosti dijagnostifikovanja, sa 2.3 miliona slučajeva (11.7%), praćen plućnim (11.4%),
kolorektalnim (10.0%), prostatnim (7.3%) i želudačnim (5.6%) karcinomima. Karcinom
pluća je ostao na mestu vodećeg uzroka mortaliteta sa 1.8 miliona preminulih (18%), praćen
kolorektalnim karcinomom (9.4%), karcinomom jetre (8.3%), želudačnim (7.7%), i
karcinomom dojke kod žena (6.9%) (1).
Očekuje se da će ukupan broj obolelih od malignih bolesti 2040. godine biti 28.4 miliona,
što je povećanje od 47% u odnosu na 2020 (1)
DETECTION OF ECHINOCOCCUS MULTILOCULARIS IN ANIMALS IN SERBIA
No full textObjectives: Alveolar echinococcosis (AE) caused by the fox tapeworm Echinococcus
multilocularis is an emerging disease in Serbia, with two confirmed cases in humans. One
objective of the Worm_Profiler project is the detection and mapping of the occurrence
of E. multilocularis in different animal species in order to gain a better understanding of
the distribution and major reservoirs.
Materials and methods: Adult worms were collected from the intestines of golden
jackals (Canis aureus) while Taeniid eggs were collected from jackal feces using a flotation
and mesh filtration technique. Tissue and cyst fluid, if present, were collected from
condemned livers of various livestock. The Echinococcus tapeworm species was
identified using a multiplex PCR for E. multilocularis, E. granulosus and E. canadensis.
Results: E. multilocularis was detected in 6,9 % of golden jackals (7/101) and one pig
liver (1/31). In terms of geographical distribution, E. multilocularis was detected near
Belgrade (Ub and Donji Tovarnik), Čajetina, Svilajnac (Grabovac), Požarevac (Ljubinje)
and Niš (Vinik).
Conclusion: In Serbia, golden jackals are major reservoirs of E. multilocularis and their
presence near towns and major cities should be regarded as a concern to public health.Book of abstract: 57th Days of Preventive Medicine, International Congress Contemporary Challenges in
Public Health, 23-26. September 2025. Niš, Serbi
Postbiotics as microbial-derived therapeutics for wound healing disorders: from molecular mechanisms to future application
No full textSkin microbiota emerged as an important factor in modulating all aspects of the wound healing process, with the potential utilization of residing microbes as biological therapeutics. Commensal or probiotic bacteria represent a first layer of the cutaneous barrier protection, inhibiting detrimental effects of pathogens and modulating cutaneous immune response. In this review, we highlight the latest findings on pro-healing ability of a new subclass of probiotic-derived products named postbiotics, defined as preparations of inanimate microorganisms and/or their components that confer a health benefit on the host. By mimicking the beneficial effect of live probiotics, postbiotics have the ability to restore healthy skin microbiome through inhibition of pathogen colonization and biofilm formation. Postbiotics also regulate skin epithelial barrier function and cutaneous immune response to suppress intracellular pathogen invasion. In order to effectively restore barrier breach, postbiotics stimulate multiple cellular components of the cutaneous wound healing process. This review describes molecular and cellular aspects of host-postbiotics interactions during cutaneous wound healing and provides a current viewpoint of therapeutic potential and advantages of postbiotics application for treatment of cutaneous wound healing disorders. In the era of rising antimicrobial resistance and epidemic proportions of wound healing disorders, probiotic-based therapeutics offer safe, effective and yet underutilized solutions for unmet clinical need
The role of SOX2 and SOX9 genes and miR-21 in phenotypical characteristics of astrocytes derived from pluripotent NT2/D1 cells
No full textAstrociti su glavne homeostatske ćelije centralnog nervnog sistema (CNS), sa jedinstvenom
sposobnošću da se aktiviraju u odgovoru na različita patološka stanja CNS-a. Poznato je da tokom
procesa aktivacije ponovo stiču određene osobine astrocitnih prekursora, uključujući ponovnu
ekspresiju regulatornih proteina SOX2 i SOX9. Iako su uloge SOX2 i SOX9 u gliogenezi poznate,
njihove funkcije u zrelim astrocitima nisu u potpunosti razjašnjene. MikroRNK (miRNK)
predstavljaju bitne regulatore različitih funkcija astrocita, pri čemu miR-21 ima značajnu ulogu u
reaktivnoj astrogliozi. Međutim, njena uloga u drugoj značajnoj fenotipskoj promeni astrocita,
senescenciji, nije poznata. Primenom lentiviralne transdukcije, imunofluorescencije i Western blot-a
na astrocitima poreklom od NT2/D1 ćelija (NT2/A) ispitane su uloge SOX2, SOX9 i miR-21 u
fenotipskim osobinama astrocita, sa fokusom na procese aktivacije i senescencije. Rezultati su
pokazali da SOX2 povećava proliferativni kapacitet NT2/A, dok SOX9 povećava migratorni
kapacitet. Takodje, pokazano je da SOX9 povećava ekspresiju NFIA i glutamatnog transportera
GLAST kao i da dovodi do povećanja kapaciteta za preuzimanje vanćelijskog glutamata u zrelim
astrocitima. Sa druge strane, utišavanje miR-21 smanjuje proliferaciju astrocita i potencijalno pomaže
njihov ulazak u senescenciju. Naši rezultati pokazuju da SOX2, SOX9 i miR-21 ostvaruju bitne uloge
u procesima aktivacije i senescencije astrocita. Razumevanje njihovog uticaja na fenotipske
karakteristike astrocita vezanih za aktivaciju i senescenciju otvara mogućnost za njihovu modulaciju
koja bi potencijalno mogla doprineti razvoju novih terapeutskih strategija za regeneraciju tkiva i
oporavak CNS-a.Astrocytes are the primary homeostatic cells of the central nervous system (CNS), with a
unique ability to reactivate in response to various pathological disorders of the CNS. During the
reactivation process, they reacquire certain characteristics of astrocytic precursors, including re-
expression of the transcription factors SOX2 and SOX9. While the roles of SOX2 and SOX9 in
gliogenesis are well known, their functions in mature astrocytes remain incompletely understood.
MicroRNAs (miRNAs) are key regulators of various astrocytic functions, with miR-21 playing a
significant role in reactive astrogliosis. However, its role in another major phenotypic change in
astrocytes, senescence, is unknown. Lentiviral transduction, immunofluorescence, and Western blot
analysis were employed to investigate the roles of SOX2, SOX9, and miR-21 in the phenotypic
properties of astrocytes derived from NT2/D1 cells (NT2/A), with the focus on the processes of
reactivation and senescence. Our results showed that SOX2 increases the proliferative capacity of
NT2/A, while SOX9 increases their migratory capacity. SOX9 also increases the expression of NFIA
and the glutamate transporter GLAST, as well as the capacity for extracellular glutamate uptake in
mature astrocytes. Silencing miR-21 reduces astrocyte proliferation and potentially promotes their
senescence. Our findings indicate that SOX2, SOX9, and miR-21 play critical roles in the processes
of astrocyte reactivation and senescence. Understanding the influence of these factors on astrocyte
phenotypic characteristics related to reactivation and senescence opens the possibility for their
modulation, which could potentially contribute to the development of novel therapeutic strategies for
tissue regeneration and CNS recovery
Core influencers and network structure of co-occurring antibiotic, metal and biocide resistance genes and mobile genetic elements in Belgrade's airborne resistome during autumn season
No full textUrban air harbors complex microbial communities carrying resistance determinants. This study
characterized the airborne resistome across seven Belgrade locations with varying pollution
during autumn season using shotgun metagenomics. We profiled antibiotic resistance genes
(ARGs), metal resistance genes (MRGs), biocides resistance genes (BRGs), and mobile genetic
elements (MGEs) via CARD, MegaRes, isfinder, integrall, and plasmid databases. Spearman
rank correlation of the top 35 elements from each category constructed co-occurrence
networks, split into positive and negative correlation subnetworks. Key elements emerged as
high-influence hubs. Betweenness centrality identified plasmid NZ_CP016737.1, ARGs
mdtF and acrD, and MRGs mntH and pstA as critical connectors in both networks. Degree
centrality highlighted overlapping hubs: ARGs (mdtB, msbA, emrB), plasmids
(NZ_MG591698.1, NZ_CP041417.1, NZ_CP077309.1, NZ_LN868944.1), genus Escherichia
sp., and MRG cusA. Crucially, eigenvector centrality identified an identical core set of the
top 10 most influential elements in both networks: ARGs mdtB, msbA, emrB; integrons
CP051219.1 and AP023197.1; genus Escherichia sp.; plasmids NZ_MG591698.1,
NZ_CP041417.1, NZ_CP077309.1, NZ_LN868944.1; and MRG cusA. Network topology
revealed stark differences. The positive correlation network exhibited high modularity (0.75),
forming distinct modules featuring the hub genera Lactococcus sp. and Escherichia sp. The
negative correlation network showed low modularity (0.30), lacking clear clustering. We
identified a persistent core of highly influential elements (specific efflux pump ARGs,
plasmids, integrons, Escherichia, and MRG cusA) dominating Belgrade's airborne resistome
network across correlation types. The dominance of Escherichia and Lactococcus as hubs
within structured positive co-occurrence modules highlight their significance in resistance
dissemination, likely driven by co-selection pressures and facilitated by MGEs.Zbornik sažetaka: V simpozijum biologa i ekologa Republike Srpske sa međunarodnim učešćem - SBERS 2025 Prirodnomatematički fakultet, Univerzitet u Banjoj Luci, 13-15. novembar 202
Integrativni pristupi u proučavanju mikroRNK: od transkriptomike i strukturne genomike do funkcionalne validacije u CAKUT
No full textCongenital Anomalies of the Kidney and Urinary Tract (CAKUT) are the most common developmental
malformations and the leading cause of chronic kidney disease in children. Although numerous point
mutations and structural variants in genes associated with CAKUT have been discovered in previous
research, they can explain only 20% of cases. This points to the existence of a more complex control of
gene function through regulatory molecules and networks of gene interactions in the development of
the urinary system. Of special note are microRNAs, small non-coding RNAs that perform fine tuning of
gene expression and whose changes in expression level have the potential to significantly affect
penetrability and expressivity of CAKUT.
This paper describes a journey in which CAKUT research became a model for understanding the potential
of microRNAs in the development of congenital anomalies. From transcriptomic discoveries and
bioinformatic integrations, through mapping of DNA regions with Copy Number Variation, to functional
experiments, a new perspective of understanding inheritance and phenotypic variability has been shaped.
Today, CAKUT is defined as a complex network of regulatory signals in which microRNAs have a potential
role as both initiators and modifiers of the disease.
The developed integrative approach shows that the integration of molecular data better explains the
molecular basis of CAKUT and opens up space for translational methods. This defines the foundations for
more precise risk stratification, monitoring the course of the disease and the development of personalized
therapeutic strategies. This framework lays the foundation for the future application of advanced molecular
methods and multi-omics analysis, as well as machine learning algorithms, in order to create predictive
models for use in the diagnosis and treatment of CAKUT.Urođene anomalije bubrega i urinarnog trakta (engl. Congenital Anomalies of the Kidney and Urinary Tract
– CAKUT) predstavljaju najčešće razvojne malformacije i vodeći uzrok hronične bubrežne insuficijencije
kod dece. Iako su dosadašnjim istraživanjima otkrivene brojne pojedinačne mutacije i strukturne varijante
u genima koji su povezani sa sa CAKUT-om, one mogu objasniti samo 20% slučajeva. To upućuje na postojanje
složenije kontrole genske funkcije preko regulatornih molekula i mreža genskih interakcija u razvoju
urinarnog sistema. Posebno se izdvajaju mikroRNK, male nekodirajuće RNK koje fino regulišu gensku ekspresiju
i čije promene u nivou ekspresije imaju potencijal da značajno utiču na penetrabilnost i ekspresivnost
CAKUT-a.
U ovom radu prikazan je put kojim je istraživanje CAKUT-a postalo model za razumevanje potencijala
mikroRNK u nastanku urođenih anomalija. Od transkriptomskih otkrića i bioinformatičkih integracija, preko
mapiranja regiona DNK sa varijabilnim brojem kopija, pa sve do funkcionalnih eksperimenata, oblikovana
je nova perspektiva razumevanja nasleđivanja i fenotipske varijabilnosti. CAKUT se danas definiše kao
složena mreža regulatornih signala u kojoj mikroRNK imaju potencijalnu ulogu i kao pokretači i kao modifikatori
bolesti.
Razvijeni integrativni pristup pokazuje da integracija molekularnih podataka bolje objašnjava molekularnu
osnovu CAKUT-a i otvara prostor translacionim metodama. Time se definišu temelji za precizniju stratifikaciju
rizika, praćenje toka bolesti i razvoj personalizovanih terapijskih strategija. Ovakav okvir postavlja
osnovu za buduću primenu naprednih molekularnih metoda i multi-omics analiza, kao i algoritama mašinskog
učenja, u cilju kreiranja prediktivnih modela za primenu u dijagnostici i lečenju CAKUT-a
Boosting Antibiotic Efficacy of Azole Drugs against Methicillin-Resistant Staphylococcus Aureus by Coordination to Rhenium Carbonyl Complexes
No full textHerein, a library of rhenium di- and tricarbonyl complexes featuring various antimicrobial azoles as monodentate ligands is synthesized and characterized. Their antimicrobial activity is evaluated against both methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), and selected compounds are also assessed for cytotoxicity, yielding promising therapeutic indices. Notably, the complexation of antifungal azoles to the rhenium core enhances antimicrobial efficacy, with a compound exhibiting up to a 32-fold improvement in minimum inhibitory concentration (MIC) values relative to the parent azole. Structure–activity relationships indicate that cationic fac-[Re(CO)3]+ complexes consistently outperform their cis-[Re(CO)2]+ counterparts, and mechanistic studies suggest that active complexes disrupt bacterial membrane integrity and interfere with the electron transport chain. Complementary small-angle X-ray scattering and in silico analysis corroborate these findings, offering insights into the mechanism of action of this family of complexes
Biodegradation and Upcycling of Bioplastics and Paper Waste by Streptomyces microflavus DG19
No full textBioplastic materials offer a sustainable alternative to the current plastic economy, as they are derived
from renewable feedstocks and/or are biodegradable. However, the efficiency of their biodegradation is
strongly dependent on the biocatalyst involved. This work explores the biocatalytic potency of strain
Streptomyces microflavus DG19 for biopolymer biodegradation. Results show that S. microflavus DG19
rapidly degrades poly(3hydroxybutyrate-co-3-hydroxyvalerate) films in liquid culture (96% weight loss in
7 days) and is capable of poly(ε-caprolactone) and cellulose degradation, however, it was unable to
degrade poly(hydroxy octanoate) (PHO) (1). Functional annotation of the strains proteome revealed a
novel extracellular depolymerase (SmPHBase) with a defined catalytic and binding domain. Molecular
docking of SmPHBase’s AlphaFold predicted structure with PHB and PHO dimer was employed to better
understand its mode of substrate recognition and analyze the enzymes potential as a bioplastic
hydrolyzing catalyst. Furthermore, soil burial tests resulted in 48%±4% and 47%±19% weight loss of a PHB-
lined paper cup and PHBV film, respectively, highlighting the applicability of S. microflavus DG19 as a composting enhancer for bioplastic and bioplastic-coated consumer goods. Moreover, S. microflavus
DG19 can utilize 3-hydroxybutyrate as a carbon source and coupled with the >30 biosynthetic gene
clusters, can offer a route for upcycling bioplastic-containing waste.Book of abstract: ESAB Congress 2025, E-Congress 2025 - November 24-26, 202
Salivary microbiome signatures of Poles and Serbians and its potential for prediction of biogeographic ancestry
No full textBiogeographical ancestry analysis is valuable in forensic investigations, especially in missing person cases or
crimes without eyewitnesses, as it helps to infer geographic origins from genetic markers. This approach enhances
forensic efforts by providing essential clues for identifying individuals with limited direct evidence.
Slavic-speaking populations are poorly distinguishable based on human genome variability. However, recent
studies show that even populations with close biogeographic origin could be differentiated based on salivary
microbiomes. Nevertheless, the salivary microbiomes of Slavs have not been characterized yet. Therefore, this
study aimed to compare the composition of the salivary microbiomes of Western and Southern Slavs’ representatives.
16S rRNA libraries from salivary microbiomes of 40 Poles (Western Slavs) and 40 Serbians (Southern
Slavs) were prepared via PCR and sequenced on the MiSeq FGx platform (Illumina), giving approximately
100,000 reads per sample. Bioinformatic and statistical analyses were performed to assess the alpha and beta
diversity of microbiomes and determine the differences in the abundance of bacterial genera between the groups
studied. Analyses of alpha (ACE, Chao1, Shannon, and Simpson) and beta (Jaccard and Bray-Curtis dissimilarity)
diversities in the salivary microbiomes clearly distinguished between Poles and Serbians. Alpha and beta diversity
metrics were significantly higher in the Serbian population. Fusobacterium, Lautropia, Porphyromonas,
Actinobacillus, Capnocytophaga, and Kingella were the most significantly increased genera in Serbians, whereas
Veillonella, Selenomonas, Megasphaera, and Atopobium were more prevalent in Poles. In summary, our study
identified significant differences in the salivary microbiomes of Poles and Serbians, with distinct microbial
signatures associated with each population. These findings highlight the potential of salivary microbiome
analysis as a tool for predicting biogeographic ancestry. Nevertheless, further analysis extended to other Slavicspeaking
populations is necessary to clarify this issue
Homophenylalanine-derived benzo[1,4]diazepine-2,5-diones are strong bacterial quorum sensing inhibitors
No full textBenzo[1,4]diazepines show a large diversity of biological activities and are still commonly used as medications against a broad range of diseases. Within our research in the field of chemo-enzymatic alkaloid synthesis, we developed a synthetic route towards close structural relatives, namely benzo[1,4]diazepine-2,5-diones. Possible antimicrobial activities of these substances are barely known up to date. We thus screened a selection of 21 of these compounds and discovered their ability to interfere with bacterial communication (quorum sensing, QS). Derivatisation of the respective substances by a refined synthetic route resulted in a generation of 9 congeners with drastically enhanced activity, setting the stage for the application of benzo[1,4]diazepine-2,5-diones, a formerly under-investigated compound class, as QS modulators. Molecular docking experiments were performed to evaluate potential protein interaction partners – LuxP, LasR, AbaI, and RhlR – which are involved in QS. The results of the docking calculations show a high energy binding site for three analogues, 5q, 15a and 15b, in the autoinducer binding-pocket of LasR, with the position of a fluorine substituent on the diazepine core structure determining the exact spatial orientation of the compounds