imagine (Institute of molecular genetics and genetic engineering)
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Pericosine A as a Marine-Derived Anticancer Agent: Molecular Targets, Bioactivity and Therapeutic Potential Through EGFR and Topoisomerase II Inhibition
No full textMarine-derived natural products have emerged as a rich source of novel anticancer compounds, often exhibiting unique mechanisms distinct from those of terrestrial origin. Pericosine A, a carbasugar metabolite isolated from Periconia byssoides, possesses a rare hybrid shikimate–polyketide framework, contributing to its structural and biological uniqueness. Despite increasing interest in marine-derived bioactives, the anticancer mechanisms and therapeutic relevance of Pericosine A remain insufficiently characterized. This review comprehensively evaluates the current knowledge on Pericosine A, including its cytotoxic activity in vitro across various human cancer cell lines, in vivo efficacy in murine leukemia models, and structure–activity relationships of natural and synthetic derivatives. Pericosine A demonstrated selective cytotoxicity against breast and glioblastoma cell lines. Mechanistic studies have reported activity toward EGFR tyrosine kinase and human topoisomerase II, indicating potential roles in disrupting oncogenic signaling and DNA topology. In vivo, Pericosine A modestly extended survival in P388 leukemia-bearing mice. Semi-synthetic analogs exhibited variable activity, with some showing reduced potency compared to the natural compound. These findings support further investigation of Pericosine A as a marine-derived anticancer scaffold with multi-target potential and underscore the need for continued preclinical development
Rekombinantna ekspresija Se1JFR esteraze iz Streptomyces sp. WAC04770 u Escherichia coli i Bacillus subtilis ekspresionoj platformi
No full textPlastika, kao sintetički polimer, predstavlja jedan od esencijalnih materijala koji se
široko koristi i ima najrazličitije primene. Plastika kao materijal poseduje mnoge prednosti u
pogledu izdržljivosti, istrajnosti, malih energetskih zahteva pri proizvodnji i niskih potreba
održavanja, karakteriše se lakoćom, otpornošću na različite vremenske uslove, niskom
toksičnošću, providnošću materijala i jednostavnim oblikovanjem (Amobonye et al., 2021;
Jenkins et al., 2019; Topakas et al., 2022). Skoro 35% proizvedene plastike je korišćeno samo
jednom, a veoma mali deo, svega 9% biva recikliran (Jenkins et al., 2019). Široka upotreba
plastike dovela je do ozbiljnih problema po životnu sredinu, nagomilavanje otpada na
deponijama dešava se velikom brzinom, zbog čega se rizik od zagađenja životne sredine
povećava svakodnevno (Jenkins et al., 2019; Topakas et al., 2022). Mnogi sintetički polimeri
nisu biorazgradivi, dugo zaostaju u prirodi i dospevaju dublje u zemljište, vodotokove i na
kraju okeane. Recikliranje ovih polimera je veliki izazov, upotrebom tradicionalnih metoda
otpuštaju se toksične materije u prirodu, koje potom nalaze put do ljudi i utiču na njihov
svakodnevni život (Jenkins et al., 2019). Predviđa se da će se na godišnjem nivou do 2040.
godine proizvoditi 800 miliona tona plastike godišnje (Lebreton & Andrady, 2019). Intenzivno
se sprovode mnoga istraživanja sa ciljem razvijanja novih plastičnih materijala, ispitivanjem
koristi plastike za čoveka, testiranjem posledica nagomilavanja plastičnog otpada kao i
postojanosti plastike u prirodi (Hartmann et al., 2019)
The Organic-Functionalized Silica Nanoparticles as Lipase Carriers for Biocatalytic Application: Future Perspective in Biodegradation
No full textOver the past three decades, organic reactions catalyzed by lipase have been extensively studied. To overcome the drawbacks of free enzymes and develop new and sustainable biocatalysts, various insoluble forms of lipases were examined. Especially interesting are lipases immobilized on silica nanoparticles (SiNPs) due to their promising unique and advantageous physicochemical properties. Therefore, the present paper presents an overview of different organic functionalization methods of SiNP surfaces to create a more favorable microenvironment for lipase molecules. Given the high commercial value of lipases in biotechnological applications, the second part of this paper highlights the key industrial sectors utilizing these nanobiocatalysts. This review discusses the key industrial applications of silica-based lipase nanobiocatalysts, including biodiesel production, flavor ester synthesis, and pharmaceutical applications such as racemization. Special attention is given to emerging technologies, particularly the use of immobilized lipases in polymer biodegradation and polymerization reactions. These advances have paved the way for innovative solutions, such as self-degrading bioplastics, which hold significant promise for sustainable materials and environmental protection. This comprehensive overview underscores the transformative potential of lipase–SiNP nanobiocatalysts in both industrial and environmental contexts
Lignocellulolytic and plastolytic potential of groundwater and sediment bacteria from the serpentinization-driven hyperalkaline springs
No full textFour serpentinization-driven hyperalkaline springs (HAS) in the Jurassic ophiolites of western Serbia, with pH values between 11.1 and 11.7, were selected to assess the lignocellulose- and plastic-degrading potential of cultivable bacteria found in both the groundwaters and sediments of the zone of emergence of the investigated occurrences. Also, the physico-chemical properties of the groundwaters and petrological and mineralogical composition of sediments were examined. The HAS investigated are cold (temperature: 14.7–19.4 °C) and low in minerals (total dissolved solids: 104.1–450.4 mg/L) and belong to the Ca2+–OH− and Ca2+, Na+–OH− genetic type. Ca2+ was the most abundant cation (39.7–132.7 mg/L), followed by Na+ (2.0–82.5 mg/L) in three and Mg (6.6 mg/L) in one HAS, respectively. OH− was the most abundant anion (24.6–123.2 mg/L), followed by CO32− (18.0–36.2 mg/L) and Cl− (12.4–71.0 mg/L) in all tested groundwaters. Binocular examination revealed that gravelly spring sediments consist predominantly of peridotite, serpentinite, carbonate and quartzite clasts, while the powder X-ray diffraction experiments identified calcite and lizardite as the main mineral phases in the silt fraction. In total, 210 groundwater and sediment isolates were screened on lignocellulose and plastic substrates, and 33.8% of all screened HAS isolates (9.1% from groundwaters and 38.4% from sediments) degraded carboxymethyl cellulose. Selected bacterial isolates were identified by partial 16S ribosomal DNA sequencing to belong to the genera Bacillus, Peribacillus, Paenibacillus and Lysinibacillus; these could have potential applications in various commercial sectors requiring cellulose degradation. All identified isolates demonstrated growth on the plastic substrates Impranil® DLN-SD (SD) and Impranil® DL 2077 (DL), while three isolates, belonging to genera Bacillus, Peribacillus and Paenibacillus, respectively, demonstrated growth on all four tested plastic substrates (SD, DL, polycaprolactone diol and bis(2-hydroxyethyl) terephthalate). These isolates should be further explored as potential candidates for bioremediation treatments of plastic-polluted groundwaters and sediments.Related to supplementary materials: [https://imagine.imgge.bg.ac.rs/handle/123456789/2674
Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
No full textObjectives: To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remodeling of damaged skin tissue in three dimensions. Methods: The scaffolds were engineered as interpenetrating polymeric networks by the crosslinking reaction of gelatin in the presence of alginate and characterized by structural, morphological, mechanical, swelling properties, porosity, adhesion to the skin tissue, wettability, and in vitro simultaneous release of the active agents. Biocompatibility of the scaffolds were evaluated in vitro by MTT test on fibroblasts (MRC5 cells) and in vivo using Caenorhabditis elegans assay. Results: The scaffolds exhibited a highly porous interconnected morphology with adjustable porosity (93–96%) and mechanical strength (1.10–2.90 MPa), hydrophilic nature with high capacity to absorb physiological fluids, and stable adhesion to the skin tissue. The obtained results of MRC5 cell viability indicate that the scaffolds are safe for biomedical applications. No mortality was detected among the Caenorhabditis elegans throughout the incubation period, indicating that the scaffolds are not toxic. The results of in vitro release study of allantoin, quercetin, and caffeic acid confirm the scaffolds’ significant potential for simultaneous release. Conclusion: The graphene oxide/gelatin/alginate scaffolds are promising candidates for non-invasive, dual ECM-mimetic, and multi-target wound therapy, offering an innovative strategy to address the complexities of wound healing process
Quorum Quenching on Titanium Surfaces: A Strategy to Reduce Virulence in Resistant Bacteria
No full textBacterial resistance is a major healthcare challenge caused by the misuse of antibiotics,
leading to ineffective treatments for infections. In orthopedics and dentistry, biofilm formation on
implants exacerbates the issue. A promising solution is quorum quenching, which disrupts
bacterial communication, with lactonase enzymes showing potential to prevent biofilm and
combat resistance.
In this work, Ti6Al4V alloy disks were polished, cleaned, and chemically treated with acid
etching and oxidation to prepare the surface (Ti6Al4V CT). After UV activation (Ti6Al4V CT+UV)
and calcium treatment (Ti6Al4V CT+UV+Ca), surfaces were functionalized with ST1 lactonase
enzyme solution using a concentration of 1000 μg/mL, creating a Ti6Al4V CT+UV+Ca+ST1 1000
sample.
The modified titanium alloy is biocompatible1 and serves as an excellent platform for
biological functionalization. Once confirmed that the enzyme functionalization was carried out
through a zeta potential analysis, real-time quantitative PCR revealed that neither the enzyme nor
the functionalized titanium samples exhibit traditional antibacterial properties. However, they
effectively reduce gene expression related to quorum sensing and virulence factor production in
Pseudomonas aeruginosa. Similar effects were not observed with E. coli and S. aureus.
This study demonstrates the potential of ST1 lactonase-functionalized Ti6Al4V alloys to
combat bacterial resistance. These findings highlight the promise of quorum quenching as a
strategy for biofilm prevention, particularly in implant applications.
1Surface modification of Ti–6Al–4V alloy for biomineralization and specific biological
response: Part I, inorganic modification. (Ferraris et al., 2011)4th Coatings and Interfaces
Online Conference
21–23 May 2025 | OnlineSession 7. The Biomedical Application of Coatings, sciforum-114086 no
From plastic waste to nutraceutical-conversion of PET containing hydrolysates to bacterial nanocellulose with pomegranate extract
No full textIntroduction: Bio-upcycling is an innovative end-of-life strategy for
polymer waste management that use the activity of microorganisms to
convert monomers and products of pre-treated polymer waste into high-value
materials. Poly(ethylene terephthalate) (PET), a leading synthetic polyester
made from petroleum-based feedstocks, currently lacks a fully sustainable
alternative that can meet global demand. Recently, biotechnological
approaches and enzymatic recycling of PET containing plastic waste have
offered the sustainable route in PET waste management. Enhancing
recycling and upcycling rates remains the most effective strategy for
achieving plastic circularity.
Experimental: This study explores the conversion of mixed plastic waste
containing PET hydrolysates—obtained through thermal pretreatment—into
bacterial nanocellulose (BNC), a promising and sustainably produced
biopolymer. Following optimization of BNC production under various static
culture conditions using PET hydrolysates as carbon source for
Komagataeibacter medellinensis ID13488, the most effective conditions, in
terms of yield, were identified and subsequently scaled up for larger
production. Elemental analysis and HPLC analysis were used for the
identification of elements and monomers and dimers, respectively. To
expand the applicative potential of BNC derived from PET-containing
plastic waste, BNC was further used for the adsorption of pomegranate peel
extract (PPE), creating a novel bioactive formulation suitable as functional
food.Key findings: Structural and compositional analyses (FTIR, HPLC)
confirmed the successful incorporation of PPE, while FESEM analysis gave
an insight into its morphology. In vitro release studies of ellagic acid and
punicalagin were performed, as well as, pH-dependent release from BNC.
Antioxidant potential was assessed using DPPH and FRAP assays, and α-
glucosidase inhibition was tested to evaluate the potential in the regulation of
blood sugar levels. Overall, this study emphasizes a circular approach in
transforming PET containing plastic waste into bacterial nanocellulose
(BNC) and further opening its potential as a nutraceutical.
Acknowledgment: This research was funded by the European Union’s
Horizon Europe EIC Pathfinder program, grant number 101046758
(EcoPlastiC).Book of Abstracts: International conference, Biobased future: green bioprocessing for innovative bioactive product
Superelastic N-centered carbon quantum dots: Synthesis and characterization
No full textCarbon quantum dots (CQDs) have highly promising properties for variety of applications as a new family member of carbon-based nanomaterials. In this paper, CQDs were synthetized by solvothermal method using nicotinamide as precursor. For the first time, we report on electron paramagnetic resonance (EPR) active CQDs with numerous unpaired N radicals at the edges of CQDs. Nanomechanical measurements revealed internal structure of CQDs that are more elastic than single wall carbon nanotubes (SWCNTs). Electrostatic force microscopy showed average amount of electrons in CQDs core and positive charge at the edges. Polymer nanocomposites based on CQDs were not cytotoxic and hemolytic whereas antibacterial testing shown good antibacterial activity. Reactive oxygen species production measurements indicated that nanocomposites were highly potent generators of reactive oxygen species with singlet oxygen yield of 0.68 and promising materials for application in biomedicine
Unraveling Osteosarcoma Heterogeneity: molecular subtyping of early-stage osteosarcoma
No full textIntroduction Osteosarcoma (OS) represents a highly heterogeneous bone malignancy. Identifying molecular subtypes can improve the understanding of tumor biology and contribute to future targeted therapies. Material and method Non-negative matrix factorization (NMF) was used to classify 102 OS samples, derived from patients who did not have metastases and did not receive chemotherapy, into three subtypes (S1, S2, S3) based on gene expression profiles. Identification of key biological processes and hub genes associated with each subtype was done using functional enrichment analysis and weighted gene coexpression network analysis (WGCNA). Tumor microenvironment (TME) analysis was conducted using ESTIMATE and CIBERSORT algorithms. Result and discussion S1 exhibited enrichment in cell cycle regulation and RNA metabolism processes, S2 in extracellular matrix organization and angiogenesis, and S3 in translation, ribosome biogenesis, and immune evasion. WGCNA identified subtype-specific gene modules. Processes enriched in the S1 group of OS are mostly connected to cellular transport, Golgi apparatus organelle functions, and cytokinesis, while the S2 correlated modules have shown enrichment mostly in extracellular matrix organization, adhesion, platelet-derived growth factor and integrin-mediated signaling. S3 subtype has shown considerable enrichment in Golgi apparatus processes, response to endoplasmic reticulum stress and bone forming processes such as ossification, bone development, etc. Analysis of the ESTIMATE score revealed differences between groups, with the lowest score exhibited by the S1 group, indicating poor prognosis for this subtype. CIBERSORT algorithm results showed different fractions of immune cells in each subtype, and correlation analyses highlighted distinct immune cell interactions in each subtype. S1 had more T follicular helper cells, eosinophils, and CD8 T cells, with the lowest M2 macrophage fraction. S2 had more resting mast cells, memory B cells, resting NK cells, and activated dendritic cells but fewer T gamma delta cells. Correlation analysis showed co-infiltration of naive T cells, T gamma delta cells, and resting dendritic cells in S1, while CD8 T cells correlated with neutrophils. In S2, activated NK and mast cells were linked, whereas S3 showed co-infiltration of M0 macrophages and naive CD4 T cells. Conclusion This study identifies three distinct OS subtypes with unique molecular signatures and immune profiles, providing potential biomarkers and therapeutic targets for personalized treatment strategies.EACR 2025 Congress
Abstract
Biofilm prevention and quorum sensing interference via surface-bound peptoid
No full textThe emergence of antibiotic resistance has ushered in a post-antibiotic era, highlighting the urgent need for alternative, cytocompatible antimicrobial strategies. Among these, antimicrobial peptides (AMPs) are promising to overcome antibacterial resistance being at the same time cytocompatible, but they are limited by fast enzymatic degradation. Peptoids are synthetic and bio-mimetic biomolecules that overcome the limitations of AMPs with resistance to proteolytic degradation. This study examined the antibacterial and cytocompatible peptoid GN2-Npm9 to reduce the risk of infection in titanium implants. Ti6Al4V samples were chemically pre-treated (CT) to favour osteointegration and functionalization. The zeta potential titration curves evidenced a mechanism of electrostatic attraction between the peptoid and CT substrate on the functionalized samples (CT_GN2-Npm9). XPS analysis and fluorescence microscopy confirmed the presence of the peptoid on CT_GN2-Npm9 and evidenced a uniform distribution. The peptoid was released in water with slow kinetics for at least 9 days (HPLC analyses). CT and CT_GN2-Npm9 specimens were subjected to biological assays against oral plaque collected from patients affected by periodontitis, showing a direct biofilm reduction of 60 % in comparison to CT and a specific effect towards pathogens as evidenced by proteomics studies. For investigating the mechanism of biofilm prevention, a culture of Pseudomonas aeruginosa was performed by conditioning the culture medium with the supernatant from the plaque test. It was observed that the biofilm of P. aeruginosa was significantly reduced due to a peptoid’s indirect effect demonstrated by the expression of genes involved in the quorum sensing network and elastase gene (lasB) that resulted in down-regulation only by the supernatants from CT-GN2-Npm9 specimens