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Synthesis, Stereochemical Determination, and Antimicrobial Evaluation of Myxocoumarin A
No full textThe myxobacterial natural product myxocoumarin A from Stigmatella aurantiaca MYX-030 has remarkable antifungal activity against agriculturally relevant pathogens. To broaden the initial evaluation of its biological potential, we herein completed the first total synthesis of myxocoumarin A. This synthetic access facilitated stereochemical investigations on the natural product structure, revealing its (R)-configuration. Biological activity profiling showed a lack of activity against Candida spp. and Gram-negative bacteria but revealed strong antibiotic activities against Bacillus subtilis and Staphylococcus aureus, including MRSA.Supporting Information : [https://pubs.acs.org/doi/10.1021/acs.joc.3c01285
Zn2+/Poly(2-Hydroxyethyl Acrylate/Itaconic Acid) Hydrogels as Potential Antibacterial Wound Dressings
No full textAntibacterial hydrogels, as an advanced approach, can create optimal conditions for wound healing, even in the fight against stubborn and difficult-to-treat wound infections. Interestingly, pH is an often neglected clinical parameter, although it has a significant impact on the wound healing process. At different stages of wound healing, the pH in the wound bed changes from slightly alkaline to neutral to acidic. To develop novel pH-sensitive antibacterial hydrogel dressings, Zn2+-loaded poly(2-hydroxyethyl acrylate/itaconic acid) hydrogels were synthesized. The hydrogels exhibit pH-sensitive swelling in the physiologically relevant pH range, with a pronounced swelling ability at neutral pH. The controlled release of Zn2+ occurs in a buffer of pH 7.40 at 37°C. The liquid transport mechanism and release kinetics are evaluated using the specific kinetic models of Ritger-Peppas and Peppas-Sahlin. The effect of Zn2+ on structural, thermal, swelling, cytocompatibility, and antibacterial properties is evaluated by Fourier transform infrared spectroscopy, differential scanning calorimetry, swelling studies, MTT, and antibacterial tests. The hydrogels show excellent antibacterial activity against Escherichia coli. The research opens new perspectives for efficient wound healing management, and the extension of the study will be orchestrated by optimising the hydrogel composition to achieve improved performance. This article is protected by copyright. All rights reserve
STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA
Get PDFBioinformatics was established at the IMGGE
in collaboration with the Beijing Genomics Institute
(BGI) and with the support of the Government of
the Republic of Serbia. The Center was founded
with the aim of accelerating the implementation
of 4P medicine (Preventive, Predictive, Personalized,
and Participatory), in our country by using the
cutting-edge tools of molecular biology and information
technology. As such, the center is unique in
Serbia and the South East Europe region.
The state-of-the-art equipment existing at the
Center (DNBSEQ-G400 (BGI), NextSeq 550Dx,
2000 and MiSeq (Illumina) Sequencing Systems;
MinION (OxfordNanopore); MGISP-9600
High-throughput Automated Sample Preparation
System) offered a wide range of application: the
whole genome and whole exome sequencing, targeted
sequencing, transcriptome sequencing and
more. The analysis of data was facilitated by the
access to the National Platform for Artificial Intelligence providing space for secure data storage, and
to a supercomputer (Nvidia), critical for processing
and analyzing Big Data.
Since its establishment more than 2000
SARS-CoV2 genomes were sequenced, 300 patient
samples undervent diagnostic work-up. Pilot project
for NIFTYPro screening was finished encompasing
58 pregnant women. First transcriptomes
and metagenomes were analyzed.
Further implementation of NGS methodology
in research and for diagnostics, and intensive
development of bioinformatics, by strengthening
the hardware and software capacities and the education
of the bioinformatics team, will lead us in
becoming driving force of the development of biomedicine
and biotechnology in Serbia, extending
collaboration beyond our borders.ABSTRACT BOOK: “Genetic Diseases from Diagnostics to Prevention and Therapy” October 05-14th Balkan Congress of Human Genetics & 9th Rare Disease SEE Meeting 2023; Skopje, October 05-07, 202
Tissue engineering as a valuable strategy for development of mimetic 3D cancer models
No full textOnline Abstract Book: Goodbye Flat Biology: Next Generation Cancer Models, Berlin, Germany, 10-12 October, 202
Supplementary information for the article: Snoch, W., Jarek, E., Milivojevic, D., Nikodinovic-Runic, J., & Guzik, M. (2023). Physicochemical studies of novel sugar fatty acid esters based on (R)-3-hydroxylated acids derived from bacterial polyhydroxyalkanoates and their potential environmental impact. Frontiers in Bioengineering and Biotechnology, 11. https://www.frontiersin.org/articles/10.3389/fbioe.2023.1112053
Get PDFWS acknowledges the support of InterDokMed project no.POWR.03.02.00-00-I013/16.We thank Marzena Noworyta1 forrepeating pH and interfacial tension measurements and conductivitymeasurements.Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1780]The Supplementary Material for this article can be found online at: [https://www.frontiersin.org/articles/10.3389/fbioe.2023.1112053/full#supplementary-material
Colistin resistance in acinetobacter baumannii: Molecular mechanisms and epidemiology
Get PDF: Acinetobacter baumannii is recognized as a clinically significant pathogen causing a wide
spectrum of nosocomial infections. Colistin was considered a last-resort antibiotic for the treatment of
infections caused by multidrug-resistant A. baumannii. Since the reintroduction of colistin, a number
of mechanisms of colistin resistance in A. baumannii have been reported, including complete loss of
LPS by inactivation of the biosynthetic pathway, modifications of target LPS driven by the addition
of phosphoethanolamine (PEtN) moieties to lipid A mediated by the chromosomal pmrCAB operon
and eptA gene-encoded enzymes or plasmid-encoded mcr genes and efflux of colistin from the cell.
In addition to resistance to colistin, widespread heteroresistance is another feature of A. baumannii
that leads to colistin treatment failure. This review aims to present a critical assessment of relevant
published (>50 experimental papers) up-to-date knowledge on the molecular mechanisms of colistin
resistance in A. baumannii with a detailed review of implicated mutations and the global distribution
of colistin-resistant strains
First Report of the Root-Knot Nematode Meloidogyne luci on Tomato in Serbia
No full textThe root-knot nematode (RKN) Meloidogyne luci (Carneiro et al. 2014) was described from Brazil, Chile, and Iran, parasitizing various crops (Carneiro et al. 2014). It was later also described from Slovenia, Italy, Greece, Portugal, Turkey, and Guatemala (Gerič Stare et al. 2017). It is considered an extremely damaging pest as it has a wide host range and infects numerous higher plants, including monocotyledons and dicotyledons as well as herbaceous and woody plants. This species was included in the European and Mediterranean Plant Protection Organization Alert List of harmful organisms. In Europe, M. luci has been detected in both greenhouse and field agricultural production (Gerič Stare et al. 2017). Furthermore, M. luci has been shown to survive winter in the field under continental and sub-Mediterranean climatic conditions (Strajnar et al. 2011). In August 2021, an official survey for quarantine RKNs in Vojvodina Province of Serbia revealed yellowing, stunning, and extensive root galls on tomato (Solanum lycopersicum L.) cultivar Diva F1 caused by an unknown Meloidogyne sp. in a greenhouse in the village of Lugovo (45°43′32.562″N, 19°08′55.168″E) near Sombor. As correct identification is essential for an effective pest management program, the next step was to identify the nematode species. Morphological characterization performed on freshly isolated females revealed perineal patterns similar to Meloidogyne incognita (Kofoid & White, 1919) Chitwood, 1949. The shape was oval to square with the dorsal arch rounded to moderately high and without shoulders. The dorsal striae were wavy and continuous. The ventral striae were smooth, and the lateral lines were weakly demarcated. The perivulval region was without striae. The female stylet was robust with well-developed knobs, and the stylet cone was slightly curved dorsally. Although morphological characteristics were highly variable, the nematode was suspected to be M. luci based on comparison with originally described M. luci and M. luci populations from Slovenia, Greece, and Turkey. Identification was achieved with subsequent species-specific PCR and sequence analysis. The nematode was determined to belong to the tropical RKN group and the M. ethiopica group using two PCR reactions as described by Gerič Stare et al. (2019). Identification was confirmed by species-specific PCR of M. luci as described by Maleita et al. (2021), and a band of approximately 770 bp was obtained. In addition, the identification was confirmed by sequence analyses. The region of mtDNA was amplified with the primers C2F3 and 1108 (Powers and Harris 1993), cloned, sequenced (acc. no. OQ211107), and compared with other Meloidogyne spp. sequences from GenBank. The determined sequence was 100% identical to an unidentified Meloidogyne sp. from Serbia, while the next highest scores were obtained for sequences of M. luci from Slovenia, Greece, and Iran, all of which had 99.94% sequence identity. In the phylogenetic tree, all M. luci sequences including the sequence from Serbia belonged to a single clade. Egg masses isolated from infected tomato roots were used to establish a nematode culture in the greenhouse, and they caused typical root galls on cultivar Maraton of tomato. The galling index assessed 110 days postinoculation was in the range of 4 to 5 according to the scoring scheme (1 to 10) for field evaluation of RKN infestations (Zeck 1971). To our knowledge, this is the first report of M. luci in Serbia. The authors hypothesize that climate change and higher temperatures could lead to much greater spread and damage to various agricultural crops in the field by M. luci in the future. A national surveillance program for RKNs in Serbia continued in 2022 and 2023. A management program to control the spread and damage by M. luci will be implemented in Serbia in 2023.
Funding: This work was financially supported by the Serbian Plant Protection Directorate of MAFWM in the frame of Program of Measures in Plant Health in 2021, the Slovenian Research Agency/Javna Agencija za Raziskovalno Dejavnost RS in the frame of Research Programme Agrobiodiversity (P4-0072), and the Ministry of Agriculture, Forestry and Food of the Republic of Slovenia in the frame of Expert Work in the Field of Plant Protection (C2337).This work was financially supported by the Serbian Plant Protection 12 Directorate of MAFWM in the frame of Program of Measures in Plant Health in 2021, the 13 Slovenian Research Agency in the frame of Research Programme Agrobiodiversity (P4-0072) 14 and the Ministry of Agriculture, Forestry and Food of the Republic of Slovenia in the frame of 15 Expert work in the field of plant protection (C2337).Suppmelentary material: [https://imagine.imgge.bg.ac.rs/handle/123456789/2801
Efekat epistatičkih interakcija između varijanti u genima za mikrornk i genima za proteine utišavajućeg kompleksa na rizik za razvoj i progresiju karcinoma prostate
Get PDFDobrijević Z., J. Karanović, D. Savić-Pavićević, G. Brajušković (2023). The effect of epistatic interactions between genetic variants located in microRNA and silencing complex genes on prostate cancer progression risk.- Genetika, Vol 55, No.1, 263-275.
Previous studies conducted in Asian and European populations have provided evidence of the association between microRNA-related genetic variants and prostate cancer (PCa) risk and/or progression. Nevertheless, the results obtained in these studies are inconsistent, which could be explained by the limitations of single-locus main effect evaluations to detect joint effects of multiple genetic variants, reflected in statistical epistases. Therefore, we conducted the analysis of potential epistatic interactions between variants located in microRNA genes and in genes encoding the components of RNA-induced silencing complex (RISC) in relation with PCa risk/aggressiveness. Raw data on genotyping results from our previous studies involving four microRNA polymorphisms and five variants in RISC genes were subjected to the exclusion of samples based on missing data criterion, followed by the re-evaluation of Hardy-Weinberg equilibrium. Afterwards, these genotyping results were included in the Multifactor dimensionality reduction (MDR) analysis. Permutation testing was conducted in order to assess statistical significance of the best models from MDR tests. MDR tests on the risk of developing PCa yielded statistically insignificant results. Nevertheless, the MDR results for comparison of PCa patients with high and low cancer progression risk were statistically significant for the analysis that included rs11614913, with the 3-locus best model comprising this genetic variant, rs7813 and rs784567. We conclude that statistical epistasis between rs11614913 in hsa-miR-196a2, rs7813 in GEMIN4 and rs784567 in TARBP2 shows association with the invasiveness of PCa.Ranije studije u evropskim i azijskim populacijama ukazale su na značajnu asocijaciju genetičkih varijanti sa efektom na funkciju mikroRNK sa rizikom za razvoj i/ili progresiju karcinoma prostate (KP). Međutim, rezultati navedenih studija su nepodudarni, za šta je jedan od mogućih razloga nemogućnost pristupa baziranih na proceni pojedinačnih efekata genetičkih varijanti da detektuju značajne zajedničke efekte više varijanti, a koji se reflektuju u statističke epistaze. Iz tog razloga, cilj naše studije bila je analiza potencijalnih epistatičkih interakcija između varijanti lociranih u genima za mikroRNK molekule i u genima za komponente utišavajućeg kompleksa indukovanog sa RNK (RISC) kao faktora rizika za razvoj i/ili progresiju KP. Rezultati genotipizacije dobijeni tokom sprovođenja naših ranijih studija, a koji uključuju podatke za četiri varijante u genima za mikroRNK i pet u genima za komponente RICS, podvrgnuti su inicijalnoj obradi podataka u smislu isključivanja uzoraka sa nedostajućim rezultatima, nakon čega je procenjeno odstupanje od Hardi-Vajnbergove ravnoteže. Rezultati su zatim analizirani metodom redukcije dimenzionalnosti višestrukih faktora (Multifactor dimensionality reduction - MDR analysis). Permutacioni testovi su sprovedeni sa ciljem procene statističke značajnosti najboljih modela iz MDR analize. Dobijeni rezultati MDR testova koji su se odnosili na rizik za razvoj KP nisu bili statistički značajni. S druge strane, MDR rezultati koji se odnose na rizik za progresiju KP bili su značajni za model koji uključuje tri lokusa: rs11614913, rs7813 and rs784567. Stoga, zaključci naše studije ukazuju na značaj epistatičkih interakcija između varijanti rs11614913 u hsa-miR-196a2, rs7813 u GEMIN4 i rs784567 u TARBP2 kao faktora koji ispoljavaju efekat na invazivnost KP
One year of newborn screening for spinal muscular atrophy – results of a Serbian pilot project
Get PDFSpinal muscular atrophy (SMA) is the most common genetic cause of death in
childhood. Innovative therapies show the greatest benefit only when administered in
the presymptomatic period, making newborn screening an ethical and medical priority
in many countries. In 2022 Centre for Human Molecular Genetics initiated a
feasibility study of the newborn screening for SMA in close collaboration with the
University Children's Hospital Tirsova, Association SMA Serbia and with financial
support from Novartis Gene Therapies, Roche and Biogen/Medis Pharma aiming to
screen up to 8000 babies from the Obstetrics and Gynaecology Clinic Narodni Front
during one year. A total of 6950 newborns were tested and SMA was confirmed in
two unrelated newborns from families with no history of SMA. A 16-month old
sibling of the first baby was also tested, even though he was completely
asymptomatic, and SMA was also confirmed. Average time between birth and the first
screen-positive result was 5 days, and 8 days between birth and final confirmation of
diagnosis. All three children received modifying therapies in less than 10 days from
final diagnosis. So far, no false-negatives have been reported among the newborns
who tested negative in the screening. As pioneers and leaders in this field, we created
synchronised work at different levels of healthcare system, established screening and
diagnostic algorithms and follow-up protocols. We are currently involved in scaling
up screening to include an additional maternity hospital and preparing the ground for
the implementation of the newborn screening for SMA as the official national
screening program.BOOK OF ABSTRACTS: 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international participation 31 May – 2 June 2023. Belgrade, Serbi
Sitagliptin Induces Tolerogenic Human Dendritic Cells
Get PDFSitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection