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Article ; Online: Micronutrients, genetics and COVID-19.

Kotur, Nikola / Stankovic, Biljana / Pavlovic, Sonja

Current opinion in clinical nutrition and metabolic care

2023 Volume 26, Issue 4, Page(s) 309–315

Abstract: Purpose of review: Marked inter-individual differences in the clinical manifestation of coronavirus disease 2019 (COVID-19) has initiated studies in the field of genetics. This review evaluates recent genetic evidence (predominantly in the last 18 ... ...

Abstract	Purpose of review: Marked inter-individual differences in the clinical manifestation of coronavirus disease 2019 (COVID-19) has initiated studies in the field of genetics. This review evaluates recent genetic evidence (predominantly in the last 18 months) related to micronutrients (vitamins and trace elements) and COVID-19. Recent findings: In patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered circulating levels of micronutrients may serve as prognostic markers of disease severity. Mendelian randomization (MR) studies did not find significant effect of variable genetically predicted levels of micronutrients on COVID-19 phenotypes, however, recent clinical studies on COVID-19 point out to vitamin D and zinc supplementation as a nutritional strategy to reduce disease severity and mortality. Recent evidence also points to variants in vitamin D receptor ( VDR ) gene, most notably rs2228570 (FokI) "f" allele and rs7975232 (ApaI) "aa" genotype as poor prognostic markers. Summary: Since several micronutrients were included in the COVID-19 therapy protocols, research in the field of nutrigenetics of micronutrients is in progress. Recent findings from MR studies prioritize genes involved in biological effect, such as the VDR gene, rather than micronutrient status in future research. Emerging evidence on nutrigenetic markers may improve patient stratification and inform nutritional strategies against severe COVID-19.
MeSH term(s)	COVID-19/genetics ; COVID-19/immunology ; COVID-19/metabolism ; Vitamin D/blood ; Vitamin D/metabolism ; Zinc/metabolism ; Micronutrients/metabolism ; Humans ; Nutrigenomics ; Vitamins/metabolism ; Trace Elements/metabolism ; SARS-CoV-2/physiology
Chemical Substances	Vitamin D (1406-16-2) ; Zinc (J41CSQ7QDS) ; Micronutrients ; Vitamins ; Trace Elements
Language	English
Publishing date	2023-05-02
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1460178-3
ISSN	1473-6519 ; 1363-1950
ISSN (online)	1473-6519
ISSN	1363-1950
DOI	10.1097/MCO.0000000000000942
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Article ; Online: The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia - a single center experience

Ristivojević Bojan / Kotur Nikola / Stanković Biljana / Gašić Vladimir / Lazić Jelena / Pavlović Sonja / Zukić Branka

Srpski Arhiv za Celokupno Lekarstvo, Vol 150, Iss 1-2, Pp 53-

2022 Volume 58

Abstract: Introduction/Objective. Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilizing microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR ... ...

Abstract	Introduction/Objective. Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilizing microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to VCR-induced peripheral neuropathy (VIPN). This study aimed to investigate the association of five variants in pharmacogenes involved in VCR metabolism with VIPN in Serbian ALL children. We also wanted to discover candidate pharmacogenomic markers of VIPN in Serbian population. Methods. PCR and sequencing-based methodology was used to detect variants in CYP3А5, CEP72, ACTG1, MIR3117, and MIR4481 genes. Statistical analyses were performed for investigating their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for the European population were extracted from public databases. Results. During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the genetic variants contributed to the occurrence of VIPN in our study. Population pharmacogenomics study did not reveal valid candidate pharmacovariants for VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable presently. Conclusion. More comprehensive approaches are needed to identify the panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed genome-wide association studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children.
Keywords	acute lymphoblastic leukemia ; pharmacogenomics ; vincristine ; vincristine-induced peripheral neuropathy (vipn) ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Serbian Medical Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular profiling of rare thymoma using next-generation sequencing

Kostic Peric Jelena / Cirkovic Andja / Srzentic Drazilov Sanja / Samardzic Natalija / Skodric Trifunovic Vesna / Jovanovic Dragana / Pavlovic Sonja

Radiology and Oncology, Vol 57, Iss 1, Pp 12-

meta-analysis

2023 Volume 19

Abstract: Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on ... ...

Abstract	Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease’s next-generation sequencing (NGS) genomic profiling.
Keywords	thymoma ; next-generation sequencing (ngs) ; snvs/indels ; meta-analysis ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Rapid progression to Richter’s syndrome in a patient with chronic lymphocytic leukemia and near-triploid karyotype

Denčić-Fekete Marija / Terzić Tatjana / Jaković Ljubomir / Đurašinović Vladislava / Đurašević-Karan Teodora / Radojković Milica / Pavlović Sonja / Bogdanović Andrija

Vojnosanitetski Pregled, Vol 80, Iss 5, Pp 454-

2023 Volume 457

Abstract: Introduction. The presence of aneuploidy in patients diagnosed with chronic lymphocytic leukemia (CLL), except trisomy 12, is considered quite uncommon. Hyperdiploidy or near-tetraploidy (occurring in 1–3% of all CLL patients) usually confer a poor ... ...

Abstract	Introduction. The presence of aneuploidy in patients diagnosed with chronic lymphocytic leukemia (CLL), except trisomy 12, is considered quite uncommon. Hyperdiploidy or near-tetraploidy (occurring in 1–3% of all CLL patients) usually confer a poor prognosis. Case report. We report a patient in a progressive phase of CLL with near–triploid karyotype. The prognosis of the disease was more precisely determined by applying the cytogenetic analysis of the karyotype and was complemented with molecular methods and pathohistological examination. The complex karyotype was accompanied by the TP53, C-MYC, and IGH gene disruptions, the most probable cause of rapid evolution into Richter’s syndrome. Conclusion. The use of comprehensive contemporary diagnostic techniques is highly recommended in patients who are in the progressive phase of CLL, primarily for the adequate choice of management strategy. The presented case confirms that aneuploidy in CLL patients indicates poor prognosis, which is in accordance with previous publications reporting on cases of CLL patients with aneuploidy.
Keywords	abnormal karyotype ; chronic lymphocytic leukemia ; disease progression ; karyotyping ; richter’s syndrome ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Military Health Department, Ministry of Defance, Serbia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients

Pravdic Zlatko / Vukovic Nada Suvajdzic / Gasic Vladimir / Marjanovic Irena / Karan-Djurasevic Teodora / Pavlovic Sonja / Tosic Natasa

Radiology and Oncology, Vol 57, Iss 2, Pp 239-

2023 Volume 248

Abstract: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti- ... ...

Abstract	Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (ABCB1), could have significant impact on the prognosis and could be used as targets for specific therapy.
Keywords	acute myeloid leukemia with normal karyotype ; bcl2 ; bax ; bcl2/bax ratio ; abcb1 ; prognosis ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia.

Gasic, Vladimir / Karan-Djurasevic, Teodora / Pavlovic, Djordje / Zukic, Branka / Pavlovic, Sonja / Tosic, Natasa

Life (Basel, Switzerland)

2022 Volume 12, Issue 11

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2022-11-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12111770
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Article: Crosstalk between Glycogen-Selective Autophagy, Autophagy and Apoptosis as a Road towards Modifier Gene Discovery and New Therapeutic Strategies for Glycogen Storage Diseases.

Andjelkovic, Marina / Skakic, Anita / Ugrin, Milena / Spasovski, Vesna / Klaassen, Kristel / Pavlovic, Sonja / Stojiljkovic, Maja

Life (Basel, Switzerland)

2022 Volume 12, Issue 9

Abstract: Glycogen storage diseases (GSDs) are rare metabolic monogenic disorders characterized by an excessive accumulation of glycogen in the cell. However, monogenic disorders are not simple regarding genotype-phenotype correlation. Genes outside the major ... ...

Abstract	Glycogen storage diseases (GSDs) are rare metabolic monogenic disorders characterized by an excessive accumulation of glycogen in the cell. However, monogenic disorders are not simple regarding genotype-phenotype correlation. Genes outside the major disease-causing locus could have modulatory effect on GSDs, and thus explain the genotype-phenotype inconsistencies observed in these patients. Nowadays, when the sequencing of all clinically relevant genes, whole human exomes, and even whole human genomes is fast, easily available and affordable, we have a scientific obligation to holistically analyze data and draw smarter connections between genotype and phenotype. Recently, the importance of glycogen-selective autophagy for the pathophysiology of disorders of glycogen metabolism have been described. Therefore, in this manuscript, we review the potential role of genes involved in glycogen-selective autophagy as modifiers of GSDs. Given the small number of genes associated with glycogen-selective autophagy, we also include genes, transcription factors, and non-coding RNAs involved in autophagy. A cross-link with apoptosis is addressed. All these genes could be analyzed in GSD patients with unusual discrepancies between genotype and phenotype in order to discover genetic variants potentially modifying their phenotype. The discovery of modifier genes related to glycogen-selective autophagy and autophagy will start a new chapter in understanding of GSDs and enable the usage of autophagy-inducing drugs for the treatment of this group of rare-disease patients.
Language	English
Publishing date	2022-09-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12091396
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Article: Molecular Biomarkers in Perthes Disease: A Review.

Spasovski, Vesna / Srzentić Dražilov, Sanja / Nikčević, Gordana / Baščarević, Zoran / Stojiljković, Maja / Pavlović, Sonja / Spasovski, Duško

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 3

Abstract: Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its ... ...

Abstract	Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.
Language	English
Publishing date	2023-01-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13030471
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Article ; Online: Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors.

Jovanović, Aleksa / Tošić, Nataša / Marjanović, Irena / Komazec, Jovana / Zukić, Branka / Nikitović, Marina / Ilić, Rosanda / Grujičić, Danica / Janić, Dragana / Pavlović, Sonja

International journal of molecular sciences

2023 Volume 24, Issue 24

Abstract: Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in ... ...

Abstract	Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an "in-house" gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like
MeSH term(s)	Humans ; Child ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Central Nervous System Neoplasms/genetics ; Central Nervous System Neoplasms/pathology ; Brain Neoplasms ; Germ Cells/pathology
Language	English
Publishing date	2023-12-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242417387
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Article ; Online: Can Pharmacogenetic Variants in

Jelovac, Marina / Kotur, Nikola / Ristivojevic, Bojan / Pavlovic, Djordje / Spasovski, Vesna / Damjanov, Nemanja / Pavlovic, Sonja / Zukic, Branka

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Systemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying a strong need for individualization of therapy. Four ... ...

Abstract	Systemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying a strong need for individualization of therapy. Four pharmacogenetic variants, namely
MeSH term(s)	Humans ; Pharmacogenomic Variants ; Genotype ; Azathioprine/therapeutic use ; Methotrexate/adverse effects ; Scleroderma, Systemic/drug therapy ; Polymorphism, Single Nucleotide ; Liver-Specific Organic Anion Transporter 1/genetics ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics
Chemical Substances	Azathioprine (MRK240IY2L) ; Methotrexate (YL5FZ2Y5U1) ; SLCO1B1 protein, human ; Liver-Specific Organic Anion Transporter 1 ; MTHFR protein, human (EC 1.5.1.20) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20)
Language	English
Publishing date	2023-05-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24108538
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