58 research outputs found
Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications
Research of inflammatory bowel disease (IBD) has identified numerous molecular players involved in the disease development. Even so, the understanding of IBD is incomplete, while disease treatment is still far from the precision medicine. Reliable diagnostic and prognostic biomarkers in IBD are limited which may reduce efficient therapeutic outcomes. High-throughput technologies and artificial intelligence emerged as powerful tools in search of unrevealed molecular patterns that could give important insights into IBD pathogenesis and help to address unmet clinical needs. Machine learning, a subtype of artificial intelligence, uses complex mathematical algorithms to learn from existing data in order to predict future outcomes. The scientific community has been increasingly employing machine learning for the prediction of IBD outcomes from comprehensive patient data-clinical records, genomic, transcriptomic, proteomic, metagenomic, and other IBD relevant omics data. This review aims to present fundamental principles behind machine learning modeling and its current application in IBD research with the focus on studies that explored genomic and transcriptomic data. We described different strategies used for dealing with omics data and outlined the best-performing methods. Before being translated into clinical settings, the developed machine learning models should be tested in independent prospective studies as well as randomized controlled trials
Genetic basis of otosclerosis
Uvod Otoskleroza je poremeÄaj koÅ”tane kapsule lavirinta i sluÅ”nih koÅ”Äica uva, koji dovodi do gubitka sluha zbog nemoguÄnosti provoÄenja zvuka. GenetiÄki uzrok otoskleroze je nepoznat. Cilj ovog rada je bio da se saÄini sveobuhvatni pregled savremenih saznanja o genetiÄkoj osnovi otoskleroze. Metode Za prikaz podataka o genetici otoskleroze koriÅ”Äen je narativni pregled literature. Rezultati Genetika otoskleroze nije mnogo izuÄavana i literaturni podaci o genetiÄkoj osnovi otoskleroze su oskudni. MeÄutim, u novije vreme, proÅ”iruju se znanja o genetiÄkoj osnovi otoskleroze. Ovde je prikazan pregled znanja o asocijaciji genetiÄkih markera i otoskleroze, koja su rezultat analiza genetiÄke povezanosti, kao i asocijativnih studija gena kandidata i sveobuhvatnih analiza genoma. ZakljuÄak Otoskleroza zbog svoje kompleksnosti nije bolest Äija Äe genetiÄka osnova biti lako rasvetljena. Analize omika i bioinformatika Äe doprineti razumevanju genetiÄke osnove otoskleroze.Introduction Otosclerosis is a disorder of the bone labyrinth and stapes resulting in conductive hearing loss. The genetic basis of otosclerosis still remains unknown. We aimed at reporting a comprehensive review of up-to-date knowledge on genetic basis of otosclerosis. Methods Narrative literature review was undertaken to summarize the data about genetics of otosclerosis. Results Genetics of otosclerosis has not been studied extensively and the literature on this topic is scarce. However, knowledge of genetic basis of otosclerosis is recently increasing. We have presented an overview of the knowledge of association of genetic markers with otosclerosis, gained from linkage analyses, candidate-gene studies, and modern high-throughput genomic studies. Conclusion Due to its complex pathophysiology, otosclerosis is not a disease whose genetic base will be easily understood. Multiple omics analysis and bioinformatics will lead to elucidation of genetic basis of otosclerosis
Interferon Gamma Alters the Phenotype of Rat Thymic Epithelial Cells in Culture and Increases Interleukin-6 Production
Rat thymic epithelial cells (TEC) in long-term culture were characterized by
anticytokeratin monoclonal antibodies (mAbs) and electron microscopy. Phenotypic
analysis performed by a large panel of mAbs showed that the highest percentage of
these cells was of the subcapsular/medullary type.
Recombinant rat interferon (IFN)-gamma up-regulated class-I and class-II MHC
expression by TEC in culture as confirmed by immunohistochemistry and flow
cytometry, but did not significantly alter other cell markers. TEC supernatants of IFN-gamma-
treated cultures showed higher interleukin-6 (IL-6) activity, compared to the
control, as determined by proliferation of the IL-6-sensitive B9-cell line. Increased IL-6
activity was probably not a consequence of increased TEC number in IFN-gammatreated
cultures because IFN did not significantly stimulate TEC proliferation in vitro. In
contrast, IL-6 significantly stimulated TEC proliferation, indicating that this cytokine is
not only a regulatory molecule for T-cell proliferation, but could also be an autocrine
growth factor for thymic epithelium
Efekti aspirina na apoptozu neutrofilnih granulocita
Neutrophils are a part of the immune system, and they are involved in host defence against microorganisms. Neutrophil granulocytes have the shortest lifespan among leukocytes, which can be modulated by cytokines and pharmacological agents. The effect of aspirin on apoptosis of inflammatory granulocytes has not been studied in detail yet, and therefore was the chosen subject of this study. Inflammatory granulocytes have been isolated from polyvinyl sponges implanted under the skin of Albino Oxford (AO) rats. Inflammatory cells that were isolated 20 hours later were more than 95% neutrophil granulocytes. The cells were cultivated 24 h with different concentrations of aspirin ranging from 1 ĀµM to 10 mM. After the cultivation period, apoptosis of neutrophils was assessed by morphological criteria, as well as by flow cytometry (after staining the cells with propidium iodide). We found that at concentrations from 0,1 mM to 2,5 mM aspirin inhibited apoptosis of granulocytes, but at 10 mM aspirin induced apoptosis of these cells.Neutrofilni granulociti su deo imunog sistema, ukljuÄenog u odbranu od mikroorganizama. Oni imaju najkraÄi životni vek meÄu leukocitima, koji se može modulisati citokinima i farmakoloÅ”kim agensima, a do sada nije ispitivan efekat aspirina na apoptozu inflamatornih granulocita. Zbog toga je u ovoj studiji ispitivan efekat aspirina na apoptozu inflamatornih neutrofilnih granulocita pacova. Inflamatorni granulociti su izolovani iz polivinilskih sunÄera, potkožno implantiranih, pacovima Albino Oxford (AO) soja. Inflamatorne Äelije, izolovane 20 sati kasnije, najveÄim delom (viÅ”e od 95 %) predstavljaju neutrofilne granulocite. Ove Äelije su kultivisane 24 sata sa aspirinom u koncentracijama od 1 ĀµM do 10 mM. Posle ovog perioda supernatanti su sakupljani i koriÅ”Äeni za merenje koncentracije NO. Äelije su bojene propidijum jodidom i apoptoza je analizirana na protoÄnom citofluorimetru, kao i pomoÄu morfoloÅ”kih kriterijuma. Ustanovljeno je da u koncentracijama od 0,1 do 2,5 mM aspirin inhibira, a samo u visokim koncentracijama (10 mM) indukuje apoptozu ovih Äelija. Aspirinom indukovana apoptoza je bila u pozitivnoj korelaciji sa smanjenom produkcijom NO
Supplementary data for the article: SmailagiÄ, A.; VeljoviÄ, S.; GaÅ”iÄ, U. M.; DabiÄ-Zagorac, D.; StankoviÄ, M.; RadotiÄ, K.; NatiÄ, M. Phenolic Profile, Chromatic Parameters and Fluorescence of Different Woods Used in Balkan Cooperage. Industrial Crops and Products 2019, 132, 156ā167. https://doi.org/10.1016/j.indcrop.2019.02.017
Supplementary material for: [https://doi.org/10.1016/j.indcrop.2019.02.017]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2832]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2835
Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations
Uvod: Kako ne postoje odobreni terapeutici za leÄenje pacijenata sa COVID-19, moguÄnost upotrebe postojeÄih lekova je postala važna. U nedostatku vremena za testiranje farmakogenomskih markera kod pojedinaca, populaciona farmakogenomika bi mogla biti od koristi u predviÄanju poveÄanog rizika za pojavu neželjenih reakcija i neuspeha leÄenja kod pacijenata sa COVID-19. Cilj naÅ”e studije bio je identifikovanje farmakogena i farmakogenomskih markera povezanih sa lekovima koji se preporuÄuju za leÄenje COVID-19, hlorokin/hidroksihlorokin, azitromicin, lopinavir i ritonavir, u populaciji Srbije i drugim svetskim populacijama. Metode: Podaci o genotipu 143 osobe srpskog porekla dobijeni su iz baze podataka prethodno formirane analizama genoma koriÅ”Äenjem TruSight One Gene Panel (Illumina). Podaci o genotipu pojedinaca iz razliÄitih svetskih populacija dobijeni su iz Projekta 1000 genoma. FiÅ”erov egzaktni test koriÅ”Äen je za poreÄenje uÄestalosti alela. Rezultati: Identifikovali smo 11 potencijalnih farmakogenomskih markera u 7 farmakogena znaÄajnih za leÄenje COVID-19. Na osnovu visoke alterativne uÄestalosti alela u populaciji Srbije i funkcionalnog efekta varijanti, ABCB1 rs1045642 i rs2032582 mogu biti znaÄajne za smanjeni klirens lekova azitromicina, lopinavira i ritonavira, a varijanta UGT1A7 rs17868323 za hiperbilirubinemiju kod bolesnika sa COVID-19 koji se leÄe ritonavirom. SLCO1B1 rs4149056 je potencijalni marker odgovora na lopinavir, posebno u populaciji Italije. NaÅ”i rezultati potvrdili su da se farmakogenomski profil afriÄke populacije razlikuje od ostatka sveta. ZakljuÄak: UzimajuÄi u obzir farmakogenomski profil specifiÄan za populaciju, preventivno testiranje farmakogena znaÄajnih za lekove koji se koriste u leÄenju COVID-19 moglo bi doprineti boljem razumevanju interindividualnih razlika u odgovorima na terapiju i poboljÅ”anju ishoda leÄenja pacijenata sa COVID-19.Background: Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations. Methods: Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher's exact test was used for comparison of allele frequencies. Results: We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alternative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world. Conclusions: Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients
Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia
Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered
Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment
Methotrexate (MTX) is one of the staples of pediatric acute lymphoblastic leukemia (ALL) treatment. MTX targets the folate metabolic pathway (FMP). Abnormal function of the enzymes in FMP, due to genetic aberrations, leads to adverse drug reactions. The aim of this study was to investigate variants in pharmacogenes involved in FMP and their association with MTX pharmacokinetics (MTX elimination profile) and toxicity in the consolidation therapy phase of pediatric ALL patients. Eleven variants in the thymidylate synthetase (TYMS), methylenetetrahydrofolate reductase (MTHFR), dihydrofolate reductase (DHFR), SLC19A1 and SLCO1B genes were analyzed in 148 patients, using PCR- and sequencing-based methodology. For the Serbian and European control groups, data on allele frequency distribution were extracted from in-house and public databases. Our results show that the A allele of SLC19A1 c.80 variant contributes to slow MTX elimination. Additionally, the AA genotype of the same variant is a predictor of MTX-related hepatotoxicity. Patients homozygous for TYMS 6bp deletion were more likely to experience gastrointestinal toxicity. No allele frequency dissimilarity was found for the analyzed variants between Serbian and European populations. Statistical modelling did not show a joint effect of analyzed variants. Our results indicate that SLC19A1 c.80 variant and TYMS 6bp deletion are the most promising pharmacogenomic markers of MTX response in pediatric ALL patients
Variants in vdr and nramp1 genes as susceptibility factors for tuberculosis in the population of Serbia
Tuberculosis (TB) is granulomatous diseases caused by Mycobacterium tuberculosis (MTB). TB is a highly infectious disease that primarily affects the lungs. One-third of human population is infected with MTB, therefore it is of utmost significance to determine the factors that influence the individual susceptibility to the disease. Host genetic factors have been recognized as essential for susceptibility to TB, since only 5% to 10% of infected individuals develop the disease. A number of candidate genes has been intensively studied, the most of which were connected with the function of macrophages, thus participating in immune response. Here we examined the gene variants of VDR (FokI) and NRAMP1 (INT4, D543N, 3'UTR) genes in aim to make the correlation between these genetic factors and risk of TB in Serbian patients. This study included 110 TB patients and 67 healthy controls. Pulmonary TB was diagnosed by clinical symptoms, radiological evidence of TB and bacteriological criteria (Culture-positive/smear-positive). Genotyping was performed using PCR-RFLP method. Our findings revealed significant prevalence of ff genotype and variant allele f of the FokI VDR gene variant in patients compared to control group. Based on the our results the carriers of ff genotype are five times more at risk to tuberculosis than carriers of FF and Ff genotype in our population. The results of analyzed SNPs in NRAMP1 gene showed no statistically significant difference in distribution of the gene variants between patient and control groups. Therefore, we could conclude that the genotype ff of the VDR gene is factor that strongly contribute to susceptibility to TB in Serbian population
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