imagine (Institute of molecular genetics and genetic engineering)
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Outcome of a Serbian pilot initiative: Spinal muscular atrophy newborn screening over a 16-month period
Get PDFBackground: Spinal muscular atrophy
(SMA) is the prevalent genetic cause of childhood
mortality. Pioneering treatments yield utmost advantages
only within the presymptomatic phase,
underlining the significance of newborn screening.
Materials and methods: In 2022, the Centre
for Human Molecular Genetics initiated a pilot
study of the newborn screening for SMA, working
closely alongside the University Children’s Hospital
Tirsova and Association SMA Serbia. The aim
was to lay the foundation for the implementation
of statewide newborn screening for SMA in Serbia
by conducting screening for ~8000 infants from the
Obstetrics and Gynaecology Clinic Narodni Front
over the course of a year.
Results: In the initial year, 6950 newborns
underwent testing, revealing SMA in two unrelated
infants and in an asymptomatic 16-month old sibling
of the first newborn. All three children received
therapeutic interventions in <1 month from birth.
To date, they have exhibited no signs of SMA,
and there have been no false-negative outcomes among the newborns who tested negative during
the screening.
As frontrunners in this field in Serbia, we
orchestrated harmonized efforts across various tiers
of healthcare, established screening and diagnostic
algorithms and follow-up protocols. In the second
year, we included a maternity hospital beyond
Belgrade, introducing sample shipping via mail
and extending screening accessibility to a greater
number of infants. This resulted in 9800 infants
undergoing testing within 16 months. Currently, we
are actively preparing for the official incorporation
of newborn screening for SMA into the national
screening program.
Conclusions: Timely detection and treatment
can transform SMA into a manageable condition.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
Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke
No full textChronic lung diseases are a major and increasing global health problem, commonly caused by cigarette smoke. We aimed to explore the antioxidant effects of lactic acid bacteria (LAB) against cigarette smoke in bronchial epithelial cells.The antioxidant effects of 21 heat-killed (HK) LAB strains were tested in cigarette smoke stimulated BEAS-2B cells and 3-D bronchospheres organoids. We showed that HK Lactiplantibacillus plantarum BGPKM22 possesses antioxidant activity against cigarette smoke, resistance to hydrogen peroxide, and free radical neutralizing activity. We demonstrated that HK BGPKM22 inhibited cigarette smoke induced expression of the Aryl hydrocarbon receptor (AhR) and Nuclear factor erythroid 2 related factor 2 (Nrf2) genes. The cell-free supernatant (SN) of BGPKM22 fully confirmed the effects of HK BGPKM22.For the first time, we revealed that HK and SN of L. plantarum BGPKM22 possess antioxidant activity and modulate AhR and Nrf2 gene expression in bronchial epithelial cells exposed to cigarette smoke
Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy
Get PDFNovel bacterial topoisomerase inhibitors (NBTIs) are new promising antimicrobials for the treatment of multidrug-resistant bacterial infections. In recent years, many new NBTIs have been discovered, however most of them struggle with the same issue - the balance between antibacterial activity and hERG-related toxicity. We started a new campaign by optimizing the previous series of NBTIs, followed by the design and synthesis of a new, amide-containing focused NBTI library to reduce hERG inhibition and maintain antibacterial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This optimization strategy yielded the lead compound 12 that exhibits potent antibacterial activity against Gram-positive bacteria, reduced hERG inhibition, no cardiotoxicity in zebrafish model, and a favorable in vivo efficacy in a neutropenic murine thigh infection model of MRSA infection
Exploring the interaction of Outer membrane vesicles (OMVs) produced by Paraburkholderia phytofirmans PsJN with Arabidopsis thaliana roots
Get PDFOuter membrane vesicles (OMVs), extracellular vesicles (EVs) produced by Gram-negative bacteria, are
increasingly recognised as promising tools in biomedicine due to their innate ability to interact with human
cells and trigger immune responses. The interaction of OMVs of plant growth-promoting bacteria (PGPB) with
plants, as well as with plant-pathogenic microorganisms, is far less explored. Considering the great
importance of PGPBs for the development of sustainable, environmentally friendly solutions in agriculture, the
study of the role of OMVs in PGPB-plant and PGPB-phytopathogen interactions holds valuable application
potential.
To investigate PGPB OMVs, we isolated and characterised OMVs produced by Paraburkholderia phytofirmans
PsJN, a PGPB strain known to enhance plant resistance to various abiotic and biotic stresses. After testing
different methods for isolating and purifying OMVs, a commercially available affinity-based column system
was selected as the most efficient. Outer membrane origin of isolated OMVs was confirmed using an essay for
detection of lipopolysaccharide (LPS).
To examine the interaction of OMVs with plant cells, Arabidopsis thaliana roots were incubated with isolated
P. phytofirmans PsJN vesicles, previously labelled with lipid binding fluorescent dye Vybrant™ DiD. Red signals
were observed, under confocal laser scanning microscope, in root hairs and root surface in DiD-OMV treated
plants, while in control-treated roots the same signals were missing. The results suggest direct contact of
OMVs with root hairs, which are necessary for nutrient acquisition and plant-microbe interactions in
rhizosphere. Our further research is focused on the characterization of OMV-associated RNA and its potential
delivery into host plant cells.Small New World 2.0 4-5 September 2023., Graz, Austri
Raw data for the article: Péter, G., Lukić, J., Alvestad, R., Horváth, Z., Nagy, Z., Rónyai, A., Bársony, P.,& Ljubobratović, U.. (2023). Nursing of Pike-Perch (Sander lucioperca) in Recirculating Aquaculture System (RAS) Provides Growth Advantage in Juvenile Growth Phase. in Animals, 13(3), 347. https://doi.org/10.3390/ani13030347
No full textRelated to published version: [https://doi.org/10.1016/j.aqrep.2023.101702]Raw data for: [https://doi.org/10.1016/j.aqrep.2023.101702]Related to supplementary materials: [
Variant rs745430558 in the SMAD4 gene promoter as a biomarker for adenocarcinoma of the pancreas
Get PDFBackground: Our previous study has identified variant rs745430558 in the SMAD4 gene promoter as potential biomarker for adenocarcinoma of the pancreas. The allele delTT (10T instead of 12T) was present in malignant pancreatic tissue with a prevalence of 88%. As analysis of cfDNA in liquid biopsy represents a noninvasive approach for the diagnosis and monitoring of malignancies, the aim of this study was to determine the presence of 12T and 10T alleles in the peripheral blood of patients with suspected pancreatic malignancy. Material and Methods: The study was performed using cell-free DNA (cfDNA) isolated from the serum of 15 patients with morphological alterations of the pancreas. The presence of 12T and 10T alleles was assessed by allele specific quantitative real-time PCR. Results: Of 15 analyzed samples, 13 were diagnosed with adenocarcinoma of the pancreas (AcP), 1 with neuroendocrine tumor (NET), and 1 with pancreatitis. The 10T allele was present in 84.7% of cases with AcP and also in the sample from the patient with NET. In patient with pancreatitis only the 12T allele was detected. Conclusion: Our research has shown that the results of liquid biopsy of patients with AcP are in agreement with tissue specimens analysis. Targeted detection of the rs745430558 10T variant in patients with suspected pancreatic malignancies could be a potential biomarker for diagnosis of AcP in the future
Violacein enhances the cytotoxic effect of commonly used chemotherapeutics on rhabdomyosarcoma cells
Get PDFInvestigati on of natural compounds showing specific toxicity to tumor cells aims to improve the efficacy
of available therapies. Our previous research demonstrated the cytotoxic acti vity of the bacterial pigment violacein
against rhabdomyosarcoma (RMS) cell lines. RMS is the most common soft tissue malignancy in children. In this
study, we evaluated the cytotoxicity of violacein on RMS cells in combinati on with conventi onal chemotherapeutics
doxorubicin, irinotecan, and vinflunine
UV-blocking sustainable food packaging based on polyhydroxyalkanoate and bacterial pigment prodigiosin
Get PDFNew film materials based on bacterial biomolecules polyhydroxyalkanoate (poly(3-
hydroxybutyrate-co-3-hydroxyvalerate) PHBV) and prodigiosin (PG) were produced by
solvent casting as a potential food packaging material. Film precursors were obtained in a
sustainable manner via microbial fermentation using waste stream-based substrates (cooking oil
and second-grade canned meat, after the expiry date). The incorporation of PG into the PHBV has
influenced the morphology and functionality of the obtained materials. PG acted as a nucleating
agent, affecting in turn PHBV/PG film surface morphology. The films were intensively colored,
transparent and blocked UV-light. An increase in PG content decreased film transparency but it
did not affect UV-blocking ability. Migration experiments have shown that films possess the
potential to release PG into lipophilic food simulant media where it has exhibited antioxidative
action. The obtained results suggest that PHBV/PG films can be potentially used as sustainable
and active food packaging materials.2nd International Conference on
Chemo and BioInformatics, ICCBIKG 2023, September 28-29, 2023 Kragujeva
Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia
Get PDFIntroduction: The long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma
transcript 1) dysregulated expression has been reported in a variety of cancers, but has been poorly investigated in chronic lymphocytic leukemia (CLL). The aim of thisstudy wasto investigate the expression
pattern of lncRNA MALAT1 in CLL, and evaluate its prognostic significance.
Methods: MALAT1 expression was analyzed in peripheral blood mononuclear cells of 114 newly-diagnosed CLL patients and 20 healthy controls by qRT-PCR, and association with clinical and biological features at diagnosis was assessed.
Results: MALAT1 was overexpressed in CLL compared to controlsamples(p<0.001). MALAT1 expression
was higher in male patients (p=0.003). It showed no correlation with age, leukocyte, lymphocyte and
platelet count, and serum β2-microglobulin, but exerted a positive correlation with hemoglobin level
(r=0.315, p=0.003) and a negative correlation with lactate dehydrogenase level (r=-0.303, p=0.004).
MALAT1 expression was higher in Binet A and B patients vs. Binet C patients (p=0.037). There was also a
trend toward higher MALAT1 expression in patients with favorable (del13q) and intermediate (normal
karyotype, trisomy12) cytogeneticsin comparison to patients with unfavorable (del11q and del17p) cytogenetics (p=0.059). In addition, high MALAT1 levels were associated with CD38-negative status
(p=0.017), but not with IGHV mutational status. While there was no association with the time to first
treatment, longer median overall survival in MALAT1 high- vs. MALAT1 low-expressing cases was observed (142 vs. 82 months, log rank p=0.032).
Conclusion: LncRNA MALAT1 is up-regulated in CLL. High MALAT1 expression at diagnosis may be associated with better prognosis
Molecular basis of thalassemia syndromes in Serbia: an update
Get PDFIntroduction: Thalassemia syndromes are heterogeneous group of hereditary anemias characterized
by defects in the synthesis of hemoglobin (Hb) polypeptide chains. These disorders comprise thalassemias and thalassemic hemoglobin variants which are predominantly caused by mutationsin a- and
b-globin genes (HBA and HBB genes). Clinical manifestations of thalassemia syndromes range from
asymptomatic thalassemia minor to severe anemia in thalassemia major cases. The aim of thisstudy was
to update our previous findings on frequency of thalassemia mutations which result from a 13-year-old
systematic survey in Serbia.
Methods: Two hundred and fourteen patients from 149 unrelated families presented with hematological parameters indicative of thalassemia syndromes were studied. Detection of α- and β-globin gene
mutations was performed using PCR and direct sequencing.
Results: Two Hb variants and twelve different β-thalassemia mutations, including two mutations previously not reported in Serbian population, were detected. Hb variant Lepore Boston-Washington wasthe
most common cause of thalassemia, with frequency of 24.3%, followed by HBB:c.316-106C>G mutation
detected in 18.1% of families. The third most frequent cause of β-thalassemia were HBB:c.118C>T and
HBB:c.93-21G>A mutations with 16.6% incidence each. Together, these four variants account for over
75% of all mutated β-globin alleles. In addition, five families affected with α-thalassemia were detected.
Conclusion: Despite the increase in cohort size by 50% between this and our previous studies, the frequency of mutations affecting HBB gene remained unchanged. Results presented in this study will update Serbian national mutation database and contribute to better understanding of geographic history
of South European and Balkan populations