imagine (Institute of molecular genetics and genetic engineering)
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Gut Microbiota as a Potential Target for Improving Immunotherapy
No full textImmune-mediated diseases, including cancer and autoimmune disorders, are a growing global health
burden. While immune checkpoint inhibitors (ICI)s and immunogenic cells have achieved significant success
in oncology, approaches involving immunosuppressive immune cells are under investigation for autoimmune
diseases. Increasing evidence highlights the gut microbiota as an important factor influencing
immunotherapy outcomes. Clinical and preclinical data show that greater microbial diversity and enrichment
of beneficial taxa correlate with improved therapeutic responses and fewer immune-related adverse
events in ICI-treated patients. Our findings demonstrated that specific members of gut microbiota associate
with the differentiation of dendritic cells (DC) with more pronounced immunogenic properties, which
could be leveraged to improve the efficacy of DC-based anti-cancer vaccines. On the other hand, by using
the animal model of multiple sclerosis, we demonstrated that the efficacy of myeloid-derived suppressor
cells (MDSC) in attenuation of the disease symptoms is followed by preservation of gut microbiota with an
immunosuppressive metabolic profile. These data support the idea that interventions based on specific
probiotics, dietary fibres, and faecal microbiota transplantation (FMT) could be used to improve the antitumor
and anti-inflammatory effects of therapies.Imunski posredovane bolesti, uključujući kancer i autoimunske bolesti, predstavljaju sve veći globalni
zdravstveni izazov. Dok su terapije sa inhibitorima imunskih kontrolnih tačaka (eng. immune checkpoint inhibitors,
ICI) i imunogenim ćelijama postigle značajan uspeh u onkologiji, pristupi zasnovani na imunosupresivnim
ćelijama istražuju se u terapiji autoimunskih bolesti. Sve veći broj studija ukazuje da je
mikrobiota creva važan faktor koji utiče na ishod imunoterapije. Klinički i preklinički podaci pokazuju da
veći diverzitet mikrobiote creva i prisustvo “korisnih” taksona koreliraju sa boljim terapijskim odgovorima
i manjim brojem neželjenih efekata kod pacijenata lečenih ICI terapijom. Naša istraživanja pokazala su da
pojedini predstavnici mikrobiote creva utiču na diferencijaciju dendritskih ćelija sa izraženijim imunogenim
svojstvima, što se može iskoristiti za unapređenje efikasnosti vakcina protiv tumora. S druge strane,
korišćenjem životinjskog modela multiple skleroze pokazali smo da je terapijska efikasnost supresorskih
ćelija mijeloidnog porekla u ublažavanju simptoma bolesti praćena očuvanjem mikrobiote sa imunosupresivnim
metaboličkim profilom. Ovi podaci podržavaju ideju da bi intervencije zasnovane na
specifičnim probioticima, dijetetskim vlaknima ili transplantaciji fekalne mikrobiote mogle doprineti
jačanju antitumorskih i antiinflamatornih efekata terapija
Multiphasic acute disseminated encephalomyelitis (MDEM) in a patient with systemic lupus erythematosus and C4A deficiency: case-based review
No full textAcute disseminated encephalomyelitis (ADEM) is a fulminant inflammatory demyelinating disorder of the central nervous system, typically triggered by an aberrant immune response to infectious agents or vaccination. While ADEM is primarily observed in the pediatric population, it can also develop in adults; however, the precise host factors that increase susceptibility to ADEM remain poorly understood. Although ADEM has occasionally been reported in association with systemic lupus erythematosus (SLE), we present, to our knowledge, the first documented case of multiphasic ADEM in a patient with monogenic SLE caused by a homozygous frameshift mutation in the C4A gene. Herein, we provide a comprehensive literature review focusing on clinical manifestations and therapeutic approaches for ADEM and its multiphasic variants in SLE. Moreover, we propose a potential pathophysiological link between inherited C4A deficiency and susceptibility to central nervous system demyelination, offering novel insight into mechanisms underlying the development of ADEM in the context of SLE
Rare co-existence of 15q26 deletion syndrome and lymphangioleiomyomatosis: diagnostic and therapeutic challenge
No full text15q26 deletion syndrome is a rare genetic condition caused by the deletion of terminal end of the long arm of chromosome 15 (Drayer’s syndrome). Clinical presentation usually implies intrauterine growth restriction, postnatal growth failure, varying degrees of intellectual disability, developmental delay, typical facial appearance, brachydactyly and diaphragmatic hernia. Lymphangioleiomiomatosis (LAM) is a rare genetic disease affecting multiple organs, which almost exclusively afflicts women. Typical presentation of LAM disease is pulmonary LAM, characterized by cyst-like destruction of pulmonary tissue, which leads to loss of pulmonary function, and if progresses further can lead to recurring pneumothoraxes. Co-existence of these two rare diseases hasn’t been reported so far. Here we report a case of the simultaneous presence of 15q26 deletion syndrome and LAM disease in a 38-year-old female. She presented with short statue, brachydactyly, pes equinovarus, microcephaly and signs of intellectual disability manifesting from birth and early childhood. At the age of 23 she starts to suffer of recurring pneumothoraxes with gradual loss of pulmonary function. CT and pathohistological findings revealed the presence of pulmonary LAM and genetic testing revealed 15q26.2 microdeletion characteristic for 15q26 deletion syndrome. Successful treatment of LAM using mTOR inhibitor Sirolimus resulted in clinical and functional improvement
Unlocking Cotinignans: Dual Synthetic Routes to Novel Auronolignans with Anticancer Potential and Mechanistic Insights
No full textThis dataset supports a study on the biomimetic synthesis of auronolignans derived from aurone sulfuretin and sinapyl alcohol. Two synthetic strategies were employed: a chemical route using silver carbonate (Ag₂CO₃) and an enzymatic route utilizing laccase from Trametes versicolor. Both approaches successfully yielded two novel auronolignans, cis-isocotinignan A (1) and trans-isocotinignan A (2). Comparative analysis revealed that the chemical method provided superior yields with fewer side products. The isolated compounds were comprehensively characterized using one- and two-dimensional NMR spectroscopy and infrared (IR) spectroscopy. The dataset comprises raw spectral data supporting structural elucidation, along with HPLC chromatograms documenting product isolation and purification.readme.txt (9.361Kb)***Dataset contents*** 1H NMR spectrum of cis-isocotininan A (1) recorded in CD3OD.csv (88.91 Kb), 1H NMR spectrum of cis-isocotininan A (1) recorded in CD3OD.png (1.04 Mb), 1H NMR spectrum of trans-isocotininan A (2) recorded in CD3OD + CDCl3.csv (89.52 Kb), 1H NMR spectrum of trans-isocotininan A (2) recorded in CD3OD + CDCl3.png (1.04 Mb), 13C NMR spectrum of cis-isocotininan A (1) recorded in CD3OD.csv (88.91 Kb), 13C NMR spectrum of cis-isocotininan A (1) recorded in CD3OD.png (1.04 Mb), 13C NMR spectrum of trans-isocotininan A (2) recorded in CD3OD + CDCl3.csv (89.52 Kb), 13C NMR spectrum of trans-isocotininan A (2) recorded in CD3OD + CDCl3.png (1.04 Mb), COSY spectrum of cis-isocotininan A (1).png (1.04 Mb), COSY spectrum of cis-isocotininan A.csv (88.91 Kb), COSY spectrum of trans-isocotininan A (2).png (1.04 Mb), COSY spectrum of trans-isocotininan A.csv (89.52 Kb), FTIR spectrum of cis-isocotininan A (1).png (1.04 Mb), FTIR spectrum of cis-isocotininan A.csv (88.91 Kb), FTIR spectrum of trans-isocotininan A (2).png (1.04 Mb), FTIR spectrum of trans-isocotininan A.csv (89.52 Kb), HMBC spectrum of cis-isocotininan A (1).png (1.04 Mb), HMBC spectrum of cis-isocotininan A.csv (88.91 Kb), HMBC spectrum of cis-isocotininan A (2).png (1.04 Mb), HMBC spectrum of trans-isocotininan A.csv (89.52 Kb), HPLC bio synthesis isocotininan A.csv (88.91 Kb), HPLC bio synthesis isocotininan A.png (1.04 Mb), HPLC chem synthesis isocotininan A.csv (89.52 Kb), HPLC chem synthesis isocotininan A.png (1.04 Mb), HSQC spectrum of cis-isocotininan A (1).png (1.04 Mb), HSQC spectrum of cis-isocotininan A.csv (88.91 Kb), HSQC spectrum of cis-isocotininan A (2).png (1.04 Mb), HSQC spectrum of trans-isocotininan A.csv (89.52 Kb), NOESY spectrum of cis-isocotininan A (1).png (1.04 Mb), NOESY spectrum of cis-isocotininan A.csv (88.91 Kb), NOESY spectrum of cis-isocotininan A (2).png (1.04 Mb), NOESY spectrum of trans-isocotininan A.csv (89.52 Kb)File readme.txt (9.361Kb) is under licence public domain CC
NLRP3 promoter methylation as a predictive biomarker for glucocorticoid response in patients with inflammatory bowel disease
No full textGlucocorticoids are used for inflammatory bowel disease (IBD) therapy; however nearly 50 % of IBD patients exhibit resistance or dependence. This study evaluates the relationship between methylation level at two CpG sites (cg21991396 and cg00448525) within NLRP3 promoter and glucocorticoid response of 94 IBD pediatrics (39 with Crohn's disease (40.4 %)) and 47 IBD adults (26 with Crohn's disease (55.3 %)). Disease activity scores were collected before the treatment, after the first full-dose reduction and after 3 months of therapy. Patients with active disease despite receiving a standard dose of prednisone were considered resistant, while those who initially responded but relapsed upon dose reduction were classified as dependent. The DNA methylation was investigated through sodium bisulfite conversion followed by pyrosequencing. In IBD adults, methylation levels at both NLRP3 CpG sites increased with patients’ age (p = 0.0038 and p = 0.0018, respectively). In IBD pediatrics, the methylation level at both CpG sites negatively correlated with the disease activity score before treatment (p = 0.031 and p = 0.072, respectively) and after 1 month of therapy (p = 0.037 and p = 0.067, respectively). Furthermore, poor glucocorticoid response after one month of therapy in pediatric patients was associated with lower methylation levels at both CpG sites (p = 0.045 and p = 0.038, respectively). Crohn’s disease patients had higher percentage of good responders compared to ulcerative colitis patients (p = 0.06). These findings indicate that NLRP3 methylation might change through patients’ lifespan and could have different clinical implications for pediatric and adult IBD forms
Exploring plastolytic and lignocellulolytic potential of microbial isolates from aquatic and soil environments
No full textDespite the long availability of lignocellulosic biomass and the recent emergence of plastics, bioprospecting for
microorganisms capable of degrading both remains limited. Such microorganisms could offer promising solutions for
addressing green waste and plastic pollution simultaneously. Over 640 microbial isolates from aquatic environments:
groundwater - GW, lakewater – LW and seawater – SW [1-3] and soil environments: vermicompost – VC and
laboratory-evolved synthetic consortia – SC, were screened for overlapping plastolytic and lignocellulolytic activity
using model substrates representative of polyester-based plastics: Impranil® DLN-SD (SD) and DL 2077 (DL),
polyethylene bis(2-hydroxyethyl) terephthalate (BHET) and polycaprolactone diol (PCL) and biomass components:
carboxymethyl cellulose (CMC), xylan (XYL), arabinoxylan (AXYL) and lignin (LIG) as sole carbon source for their
growth, predominantly under aerobic conditions. Approximately 70% and 83% of all screened isolates demonstrated
growth on at least 3 different tested plastic and lignocellulosic substrates, respectively. Between 94% and 100% of all
screened SW isolates could grow on each tested plastic substrate, while all screened VC isolates grew on SD and DL
substrates. All screened isolates from LW, VC and SC demonstrated growth on all tested lignocellulosic substrates. In
the screening, substrate-degrading isolates, that are of potential biotechnological interest, were most frequently detected
on CMC and SD (1:5 and 1:6 screened isolates, respectively) and least frequently on LIG and BHET (1:125 and 1:333,
respectively). Over 79% of all detected plastic- (SD, BHET) and CMC-degrading isolates were from water
environments, mainly GW, with CMC-degrading activity in GW observed predominantly in sediment isolates and in
one GW occurrence with confirmed hydraulic connection with surface water. Nearly all of XYL and LIG degradation
(93% and 100%, respectively) was observed in studied soil isolates. Of 71 (44 GW and 27 soil) substrate-degrading
isolates that were identified by partial 16S rDNA sequencing, Pseudomonas (25%), Bacillus (16%) and Acidovorax
(11%) were the most represented genera among identified GW isolates, while Streptomyces (52%), Stenotrophomonas
(19%) and Pseudomonas (11%) were the most represented genera among identified soil isolates. Of these, 2 GW and
18 VC isolates demonstrated simultaneous plastolytic and lignocelullolytic activity in the screening. In conclusion,
water environments harbour microorganisms capable of plastic degradation and should be more often included in
bioprospecting efforts. Identified isolates with simultaneous plastolytic and lignocellulolytic activities may be of
potential biotechnological interest and their genomes will be further explored in silico to identify potential enzymatic
candidates involved in this overlapping activity.E-book: 19th International Conference on Chemistry and the Environment ICCE 2025
Belgrade 8-12 June 202
Sustainable eco-friendly active packaging from food processing waste: Recycled starch and pomegranate peel extract for biodegradable solutions
No full textReducing plastic usage and improving food preservation are critical steps toward a more sustainable future, and
converting food waste into eco-friendly food packaging offers a promising solution to both challenges [1]. Food
packaging is essential for safeguarding food from spoilage and microbial growth, with active packaging technologies
providing an effective means of extending shelf life. While plastic packaging is commonly chosen for its affordability
and strong mechanical and barrier properties, its environmental persistence and limited biodegradability pose significant
sustainability issues. In response, there has been growing interest in biopolymers as an alternative to synthetic plastics,
offering both environmental benefits and the potential to retain desirable packaging qualities.
This study focuses on developing advanced, sustainable food packaging materials derived from food processing waste.
Specifically, recycled starch from potato chip factory waste and poly(vinyl alcohol) (PVA) were combined to create an
active food packaging material. To enhance the packaging's functionality, pomegranate peel extract (PPE), typically
discarded during fruit juice production, was incorporated for its natural antioxidant and antimicrobial properties.
Additionally, in a fermentation process conducted in an 8-channel bioreactor, recycled starch served as a growth medium
for Streptomyces anulatus BV365 producing actinomycin D (ActD)2, a bioactive compound with antimicrobial effects,
to further boost the material’s effectiveness.
The study produced several novel packaging materials with varying PPE concentrations (5% and 10%), along with a
control sample without PPE, using glycerol as a plasticizer. The incorporation of PPE and ActD enhanced the
packaging’s ability to extend food shelf life by imparting antioxidant and antimicrobial properties. Meanwhile, the
starch-PVA blend, contributes to the biodegradability of the packaging. The materials were characterized using a range
of analytical techniques, including Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy
(SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), wettability and water contact angle (WCA)
measurements. FTIR analysis confirmed the successful incorporation of PPE and ActD, while the addition of PPE
improved the mechanical strength and swelling behavior of the starch-PVA based materials at both 5 and 10 wt%
concentration. These findings demonstrate that the combination of enhanced functionality with environmental
sustainability makes these bio-based packaging materials a promising alternative for reducing plastic waste while still
preserving food quality.E-book: 19th International Conference on Chemistry and the Environment ICCE 2025 Belgrade 8-12 June 202
Effect of the overexpression of the GGP1 gene on cell wall remodelling and redox state in the tomato fruit
No full textTomato fruit ripening is a complex physiological process that involves morphological, anatomical, biochemical, and molecular alterations. One of these changes occurring during ripening is the softening of the fruit, which is attributed to modifications in the biosynthesis and degradation of individual cell wall components, i.e. polysaccharides and proteoglycans. In addition, ripening is affected by redox processes, and interplay of the reactive oxygen species (ROS) and specific antioxidants, enzymes, ascorbate, and phenolic compounds. The present study aims to determine the impact of the overexpression of the GDP-l-galactose phosphorylase (GGP1) gene under the control of two fruit-specific promoters, namely PPC - phosphoenolpyruvate carboxylase and PG - polygalacturonase on cell wall properties, activities of H2O2-regulating enzymes and the abundance of phenolic compounds. PPC-GGP1 and PG-GGP1 transgenic lines revealed significant structural changes in fruit parenchyma, compared to wild type fruit, followed by a disturbance in the spatial distribution and molecular & chemical composition of homogalacturonans. In addition, cell wall-bound monolignol, p-coumaryl alcohol was higher in transgenic fruit compared with wild type ones. Lastly, the catalase and ascorbate peroxidase activities were lower in PPC-GGP1 fruits, indicating changes in the regulation of antioxidative defense during the ripening process of this line. These results suggest that overexpression of the GGP1 gene affects the cell wall remodelling and redox state in the red ripe tomato fruits
Guided by tumor engineering principles: a biomimetic 3D in vitro osteosarcoma model
No full textIntroduction
Osteosarcoma is the most common primary bone cancer with a tendency
to metastasize to distant organs which results in a poor prognosis
for the patients. The scarcity of novel therapeutics could be
attributed to the continuous heavy reliance on cell monolayers and
animals for anticancer drug assessments even though over 90% of
drug candidates ultimately fail in human trials. Therefore, our aim
was to apply tumor engineering principles using biomimetic scaffolds
and bioreactors to develop a robust 3D in vitro osteosarcoma
model to serve as a physiologically relevant tool in preclinical drug
testing.
Methods
The model is based on macroporous composite scaffolds (2 wt.%
alginate, 2 wt.% hydroxyapatite) to replicate bone, in combination
with a perfusion bioreactor “3D Perfuse” (Innovation Center at the
Faculty of Technology and Metallurgy, Belgrade, Serbia) which provides
relevant biomimetic conditions. Murine K7M2-wt osteosarcoma
cells were seeded on scaffolds (discs 10 mm in diameter, 4
mm thick, 15x106 cells/cm3 of the scaffold volume) and cultivated
under static conditions for 1 day. Cell cultivation was continued in a
perfusion bioreactor under continuous medium flow of 0.27 ml/min
(corresponding to the superficial velocity of 40 lm/s), while static
cultures served as control. Biological characterization included cell
metabolic activity tests, histology (hematoxylin & eosin – H&E,
Masson’s trichrome and reticulin staining), tubulin staining and
analysis of the expression of several genes. Additionally, oxygen
and nutrient mass transport within scaffolds was mathematically
modeled under both static and perfusion conditions.
Results
Osteosarcoma cells remained metabolically active expressing pluripotency-
associated genes during short-term cultivation, especially
under perfusion conditions. The cells tended to spontaneously selfassemble
into compact, spheroid-like structures with slightly larger
average size under perfusion conditions compared to static (140 lm
vs. 120 lm in diameter). Besides, in perfusion cultures, more reticulin
fibres were observed indicating a stronger cell commitment to
secrete extracellular matrix and these cells also expressed higher
amounts of intracellular protein tubulin. Under perfusion, cell aggregates were uniformly distributed across the scaffolds and were
more numerous compared to static cultures, in which cell aggregates
were concentrated in the upper part of the scaffold. This difference
in cell aggregate distribution was correlated with significantly less
effective mass transport under static conditions highlighting the
importance of perfusion in the cell culture. Elongated and more
irregular shape of cell aggregates under perfusion conditions compared
to static was attributed to the presence of shear stresses, calculated
to be around 2 mPa on average.
Conclusions
Application of tumor engineering principles based on the use of
macroporous scaffolds imitating bone tissue and perfusion bioreactor
providing efficient mass transport at adequate shear stresses
invoked spontaneous aggregation of osteosarcoma cells into compact
spheroid-like structures over only 7 days of cultivation. The cell
aggregates were distributed throughout the scaffold volume providing
simultaneous studies of a statistically relevant number of aggregates
even in a single scaffold. Further steps in evaluation of this
model will include long-term cell cultures as well as anticancer drug
efficacy assessment
Metagenomic insight into airborne pathogenic microorganisms community and antibiotic resistomes in Belgrade during spring season
No full textIntroduction: In recent years, it has been recognized that air is an important transmission
route for antibiotic resistance genes (ARGs). In addition, airborne pathogens could be
part of particle matter (PM2.5), which is an indicator of air pollution. The intertwining of
these two serious health threats poses an additional risk to public health.
Objective: To examine the abundance and diversity of pathogens and resistomes in air
samples collected during the spring season of 2024 at two locations in the Belgrade
metropolitan area selected as highly polluted during the heating season.
Method: Outdoor air was sampled at two locations (Borca and Zemun Ugronovacka)
using polyethersulfone membrane filters (air volume of 30 m3). Collected DNA samples
were subjected to shotgun metagenome sequencing (Illumina Novaseq X plus) and
bioinformatic analysis (Novogene, UK). Pathogens and ARGs were annotated using PHI
and CARD databases, respectively.
Findings: Both airborne metagenomes showed similar patterns of significant human and
animal pathogens (Salmonella enterica, Pseudomonas aeruginosa, Staphylococcus
aureus, Mycobacterium tuberculosis, Escherichia coli, Acinetobacter baumannii), and
plant pathogens (Xanthomonas oryzae, Fusarium graminearum, Xanthomonas
campestris, Erwinia amylovora). The most abundant ARG in the airborne metagenomes
was blaTEM, but genes conferring resistance to aminoglycosides (aac(2’)-Ic), beta-lactams
(blaOXA-129, blaC, cepA, cfxA2), fluoroquinolones (mfpA), fosfomycin (murA), macrolides
(ermF, mphE), tetracyclines (tet(Q)), vancomycin (vanH, vanT, vanY, vanW) and
disinfectants (cepA, qacG) were also detected. Moreover, the gene encoding multidrug
resistant efflux pump adeF was present in both metagenomes.
Conclusion: This study revealed that Belgrade air could represent a reservoir for
pathogenic microorganisms and antimicrobial resistance.Book of abstract: FEMS MICRO 2025: Congress & Exhibition, taking place in Milan, Italy, from 14-17 July 2025