imagine (Institute of molecular genetics and genetic engineering)
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Weryfikacja markerów insercyjno-delecyjnych (InDels) i mikrosatelitarnych (STR) jako narzędzi pomocniczych do wnioskowania o pochodzeniu populacji słowiańskiej
Get PDFGenetic markers for the prediction of biogeographical ancestry have proved to be effective tools for law enforcement agencies for many years now. In this study, we attempted to assess the potential of insertion-deletion markers (InDel) and microsatellites (STRs) as subsidiary polymorphisms for inference of Slavic population ancestry. For that purpose, we genotyped Slavic-speaking populations samples from Belarus, the Czech Republic, Poland, Serbia, Ukraine and Russia in 46 InDels and 15 STRs by PCR and capillary electrophoresis and analyzed for between-population differentiation with the use of distance-based methods (FST, principal component analysis and multidimensional scaling).Additionally, we studied a sample from a Polish individual of well-documented genealogy whose biogeographic ancestry had previously been inferred by commercial genomic services using autosomal single nucleotide polymorphisms (SNPs), mitochondrial DNA and Y-SNP markers. For comparative purposes, we used genotype data collected in the “forInDel” browser and allele frequencies from previously published papers. The results obtained for InDels and STRs show that the Slavic populations constitute a genetically homogeneous group, with the exception of the Czechs differing clearly from the other tested populations. The analysis of the known Polish sample in the Snipper application proves the usefulness of the InDel markers on the continental level only. Conversely, microsatellites not only improve prediction, but are also informative if considered as an independent set of ancestry markers.Markery genetyczne do przewidywania pochodzenia biogeograficznego od wielu lat okazują się skutecznymi narzędziami dla organów ścigania. W tym badaniu podjęliśmy próbę oceny potencjału markerów insercyjno-delecyjnych
(InDel) i mikrosatelitarnych (STR) jako pomocniczych polimorfizmów do wnioskowania o pochodzeniu populacji
słowiańskiej. W tym celu genotypowaliśmy próbki populacji słowiańskojęzycznych z Białorusi, Czech, Polski, Serbii,
Ukrainy i Rosji w w zakresie 46 markerów InDel oraz 15 loci STR za pomocą PCR i elektroforezy kapilarnej oraz
analizowaliśmy pod kątem różnicowania między populacjami za pomocą metod bazujących na dystansach genetycznych (FST, analiza głównych składowych i skalowanie wielowymiarowe). Dodatkowo zbadaliśmy próbkę mężczyzny
z populacji polskiej o dobrze udokumentowanej genealogii, którego pochodzenie biogeograficzne zostało wcześniej
ustalone przez komercyjne usługi genomiczne przy użyciu autosomalnych polimorfizmów pojedynczych nukleotydów (SNP), mitochondrialnego DNA i markerów Y-SNP. Do celów porównawczych wykorzystaliśmy dane genotypowe zebrane w przeglądarce „forInDel” i częstości alleli z wcześniej opublikowanych artykułów. Uzyskane wyniki
dla InDels i STR wskazują, że populacje słowiańskie stanowią grupę genetycznie jednorodną, z wyjątkiem Czechów
wyraźnie różniących się od pozostałych badanych populacji. Analiza znanej polskiej próbki w aplikacji Snipper
dowodzi przydatności markerów InDel jedynie na poziomie kontynentalnym. Z kolei, mikrosatelity nie tylko poprawiają wyniki predykcji, ale są informatywne jako niezależny zestaw markerów pochodzenia biogeograficznego
Potential of environmental Serratia from herbicide treated soil for pathogenicity in humans
Get PDFSoils contain microorganisms capable of causing diseases in humans, either
as opportunistic or as obligate pathogens. The application of herbicides
increases the prevalence of antibiotic resistance genes and mobile genetic
elements, which expands the competitive niche of pathogenic microbes. This
implies that herbicides could impose selective pressure driving the spread of
antibiotic resistance and therefore making heavily herbicide treated agricultural
soil a possible reservoir of multiresistant opportunistic human pathogens.
From the soil exposed to chlorinated aromatic herbicides S-metolachlor
and isoxaflutole, semi-persistent selective herbicides widely used in
European Union and Serbia we isolated bacteria able to grow on herbicide as
the sole carbon source. Bacterial isolates were assessed for various virulence
traits and resistance to antibiotics in order to identify the strains with high
pathogenic potential
Supplementary data for the article: Milinčić, D., Stanisavljević, N., Kostić, A., Gašić, U., Stanojević, S., Tešić, Ž.,& Pešić, M.. (2022). Bioaccessibility of Phenolic Compounds and Antioxidant Properties of Goat-Milk Powder Fortified with Grape-Pomace-Seed Extract after In Vitro Gastrointestinal Digestion. in Antioxidants, 11(11), 2164. https://doi.org/10.3390/antiox11112164
Get PDFSupplementary material for: [https://doi.org/10.3390/antiox11112164]Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/2064
Prognostic relevance of autophagy-related markers p62, LC3, and Beclin1 in ovarian cancer
Get PDFAim To analyze the expression of autophagy markers p62,
LC3, and Beclin1 in ovarian cancer tissue and evaluate the
prognostic potential of these markers.
Methods The study enrolled 328 patients: 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. The expression of p62, LC3, and Beclin1 was analyzed in central
and invasive tumor segments with immunohistochemistry
combined with tissue microarray. The expression levels of
the analyzed markers were correlated with relevant histopathology parameters.
Results The expression of all analyzed markers was most
remarkable in epithelial ovarian carcinoma. There was a
strong positive correlation between the expressions of p62
and LC3, while these two markers negatively correlated
with Beclin1. High-grade serous carcinoma had higher p62
and LC3 levels, and lower Beclin1 levels than other tumor
types. This expression profile was also observed in more
advanced tumor stages.
Conclusion Prominent p62 and LC3 expression in combination with weak Beclin1 expression in high-grade serous
carcinoma indicates potential for the application of autophagy inhibitors in patients with this tumor subtype
Pilot proteomic study of locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy indicates high metabolic activity in non-responders' tumor tissue
No full textPurpose In the search for candidate predictive biomarkers to evaluate response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, only a few studies report proteomic profiles of tumor tissue before and after nCRT. The aim of our study was to determine differentially expressed proteins between responders and non-responders before and after the therapy in order to identify candidate molecules for prediction and follow-up of response to nCRT. Experimental Design The study has included tissue sections of rectal tumor and non-tumor mucosa from five responders and five non-responders taken before and after nCRT from patients with locally advanced rectal cancer. Extracted proteins were analyzed by LC-MS/MS analysis followed by a set of bioinformatics analyses. Result Proteomics analysis provided a mean of approximately 1050 protein identifications per sample. A comparison of proteomic profiles between responders and non-responders has identified 18 differentially expressed proteins. Pathway analysis demonstrated high metabolic activity in non-responders' tumors before nCRT, indicating the presence of intrinsic chemoradioresistance in these subjects. Two proteins associated with poor prognosis in colorectal cancer, ADAM10 and CAD, were identified as candidate predictive biomarkers as they were present in non-responders only. Conclusions and Clinical Relevance Shortlisted proteins from our study should be further validated as candidate biomarkers for response to routinely applied nCRT protocols
The new exopolysaccharide produced by the probiotic strain L. reuteri B2: extraction, biological properties, and possible application for Ni2+ ion removal from the contaminated water
No full textAs one of the most promising groups of microbes, lactic acid bacteria (LAB) can synthesize metabolites that can be used in different industries over the world, mainly in the pharmaceutical, food, and dairy industries. In this study, a novel exopolysaccharide was extracted and isolated from the probiotic strain Lactobacillus reuteri B2, and assessed on biological activity and its possible application as a biosorbent for the removal of Ni2+ ions from contaminated water. New exopolysaccharide was characterized using FTIR, SEM, XRD, NMR, MALDI-TOF MS, and TGA/DTG analysis. Biological assays included antioxidative activity, cytotoxic assay, and adhesion assay of L. reuteri B2 to HT29 cells. Our hypothesis was that if this exopolysaccharide is nontoxic, it can be used as a novel biomaterial for the possible application of the removal of Ni2+ ions from contaminated water. The scavenging effect of nontoxic exopolysaccharide was 76% at 2 mg/mL using ABTS assay, in biological assays, while the removal efficiency of nickel from the aqueous solution was 92.96% in biosorption study. According to these results, this exopolysaccharide can be considered a very promising biomaterial for potential application in different industries, from pharmacy to wastewater treatments.Supplementary material:[https://imagine.imgge.bg.ac.rs/handle/123456789/2818
Bioactivities of Salvia nemorosa L. inflorescences are influenced by the extraction solvents
No full textSalvia nemorosa L. is a rich source of bioactive constituents. We have used different solvents to obtain 14 different extracts in order to evaluate solvents impact on S. nemorosa inflorescences bioactivities. Firstly, the extraction yield, chemical composition and cytotoxic properties towards HaCaT cell line were elaborated. Afterwards, we have studied the extracts bioactivity in terms of wound healing, antioxidant and antidiabetic potentials as well as antimicrobial and antibiofilm capacities; followed by the determination of the antimicrobial mechanism. The extracts yield ranged from 3.03% to 15.75% and they were dominated by epigallocatechin gallate and rosmarinic acid. The majority of extracts did not possess cytotoxic properties towards human keratinocytes. Butanol was the most appropriate solvent for the improvement of wound healing capacity. Combined extraction with ethanol and water resulted in the highest antioxidant potential of the extracts that could be attributed to the high abundance of detected polyphenols. Extraction with butanol led to the increased inhibition towards enzymes linked to type 2-diabetes and increase in antimicrobial capacities. The extracts have shown antibiofilm potential towards Staphylococcus lugdunensis biofilms with more than 90% inhibition for the most active ones. The selected extract EB7 reduced bacterial ability to adhere to human keratinocytes and provided immunomodulatory action in HaCaT cells exposed to S. lugdunensis. The antibacterial mechanism of action of the same extract was associated with moderate perturbation in the cell membrane integrity and with the reduction in bacterial mitochondrial activity. S. nemorosa inflorescences were abundant sources of bioactive polyphenols and with different extraction solvents their bioactivities were further improved. This study reported for the first time the effects of extraction solvents on various bioactivities of S. nemorosa inflorescences, supporting S. nemorosa role as a natural bioactive therapeutic agent with possible antioxidant, antidiabetic and antimicrobial applications
Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis (vol 49, pg 598, 2022)
Get PDFJ Rheumatol 2022; doi: 10.3899/jrheum.210931
In the Methods section, under the subheading “Follow-up and study outcome,” the last sentence should be as follows: “All new DUs were recorded by contacting all 39 patients once every 1–3 months during follow-up.” The error does not affect the results or conclusions of the study.
This correction only applies to the April 1 First Release. The correct text appears in the print and online issues
Cysteine Peptidase Cathepsin X as a Therapeutic Target for Simultaneous TLR3/4-mediated Microglia Activation
Get PDFMicroglia are resident macrophages in the central nervous system that are involved in immune responses driven by Toll-like receptors (TLRs). Microglia-mediated inflammation can lead to central nervous system disorders, and more than one TLR might be involved in these pathological processes. The cysteine peptidase cathepsin X has been recognized as a pathogenic factor for inflammation-induced neurodegeneration. Here, we hypothesized that simultaneous TLR3 and TLR4 activation induces synergized microglia responses and that these phenotype changes affect cathepsin X expression and activity. Murine microglia BV2 cells and primary murine microglia were exposed to the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)) and the TLR4 ligand lipopolysaccharide (LPS), individually and simultaneously. TLR3 and TLR4 co-activation resulted in increased inflammatory responses compared to individual TLR activation, where poly(I:C) and LPS induced distinct patterns of proinflammatory factors together with different patterns of cathepsin X expression and activity. TLR co-activation decreased intracellular cathepsin X activity and increased cathepsin X localization at the plasma membrane with concomitant increased extracellular cathepsin X protein levels and activity. Inhibition of cathepsin X in BV2 cells by AMS36, cathepsin X inhibitor, significantly reduced the poly(I:C)- and LPS-induced production of proinflammatory cytokines as well as apoptosis. Additionally, inhibiting the TLR3 and TLR4 common signaling pathway, PI3K, with LY294002 reduced the inflammatory responses of the poly(I:C)- and LPS-activated microglia and recovered cathepsin X activity. We here provide evidence that microglial cathepsin X strengthens microglia activation and leads to subsequent inflammation-induced neurodegeneration. As such, cathepsin X represents a therapeutic target for treating neurodegenerative diseases related to excess inflammation
Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation
No full textSynthesis of protulactone A (PLA, 1) and twelve of its analogues have been achieved starting from D-galactose. PLA was isolated in the crystalline state, and its crystal structure was determined utilizing X-ray crystallography, which confirmed the assumed stereochemistry at all stereocenters. All tested compounds displayed antiproliferative activity against a panel of tumour cell lines, and all of them were non-cytotoxic toward the normal cells (MRC-5). Natural product PLA (1) was the most active against the K562 and MCF-7 cell lines (IC50 6.52 and 2.20 μM, respectively). Some of the synthesized derivatives showed very potent cytotoxicity, especially analogues 11, 13 and 15 (IC50 1.08–1.14 μM against MCF-7), and 9 and 14 (IC50 1.29 and 1.64 μM against K562). SAR analysis indicated important structural motifs for antiproliferative activity. Unfortunately, PLA (1), its C-7 epimer (2) and demethylated analogue (3) did not display a significant antimicrobial activity (two Gram-positive and two Gram-negative bacteria and one fungal strain) and they also cannot affect the ability to modulate bacterial communication