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  1. Article ; Online: Novel Insights into the Effects of Genetic Variants on Serum Urate Response to an Acute Fructose Challenge: A Pilot Study.

    Zhang, Xinruo / Mass, Baba B / Talevi, Valentina / Hou, Ruixue / North, Kari E / Voruganti, Venkata Saroja

    Nutrients

    2022  Volume 14, Issue 19

    Abstract: Studies have shown that genetic variations can influence metabolic response to nutrient intake, and that diets rich in fructose contribute to hyperuricemia. In this pilot study, our aim was to determine the variability of serum urate in response to an ... ...

    Abstract Studies have shown that genetic variations can influence metabolic response to nutrient intake, and that diets rich in fructose contribute to hyperuricemia. In this pilot study, our aim was to determine the variability of serum urate in response to an acute fructose challenge and to investigate if genetic variants would affect this response in young to middle-aged adults who self-reported as Black or White. Fifty-seven participants consumed a fructose-rich beverage after an overnight fast. Blood was drawn at five time points (baseline, 30, 60, 120, and 180 min after consumption). Thirty urate-related single nucleotide polymorphisms (SNPs) were analyzed for their associations with baseline serum urate and its percent changes, using a two-step modeling approach followed by meta-analysis. At baseline, serum urate (mg/dL, mean ± SD) was higher in Whites (5.60 ± 1.01 vs. 5.37 ± 0.96), men (6.17 ± 1.14 vs. 5.24 ± 0.79), and those with obesity (5.69 ± 1.08 vs. 5.42 ± 1.06 vs. 5.34 ± 0.80). Three SNPs were significantly associated with baseline serum urate or its percent changes, and six SNPs were nominally associated with percent changes in serum urate. In summary, our results showed that genetic variants could play a role in short-term urate metabolism.
    MeSH term(s) Adult ; Fructose/pharmacology ; Gout ; Humans ; Hyperuricemia/genetics ; Male ; Middle Aged ; Pilot Projects ; Risk Factors ; Uric Acid
    Chemical Substances Uric Acid (268B43MJ25) ; Fructose (30237-26-4)
    Language English
    Publishing date 2022-09-28
    Publishing country Switzerland
    Document type Journal Article ; Meta-Analysis
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu14194030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Identification of single nucleotide pleomorphisms associated with periodontal disease in head and neck cancer irradiation patients by exome sequencing.

    Talevi, Valentina / Wen, Jia / Lalla, Rajesh V / Brennan, Michael T / Mougeot, Farah B / Mougeot, Jean-Luc C

    Oral surgery, oral medicine, oral pathology and oral radiology

    2020  Volume 130, Issue 1, Page(s) 32–42.e4

    Abstract: Objective: Periodontal disease (PD) is a common oral complication in patients with head and neck cancer (HNC) undergoing radiation therapy (RT). Our objective was to identify candidate single nucleotide polymorphisms (SNPs) associated with PD in ... ...

    Abstract Objective: Periodontal disease (PD) is a common oral complication in patients with head and neck cancer (HNC) undergoing radiation therapy (RT). Our objective was to identify candidate single nucleotide polymorphisms (SNPs) associated with PD in radiation-treated patients with HNC.
    Study design: DNA was extracted from the saliva of patients with HNC (n = 69) before RT. Clinical attachment loss (CAL) increment greater than 0.2 mm over 24 months after RT was used to define PD progression. After exome sequencing, SNPs associated with post-RT PD progression were identified by using logistic regression and homozygosity analyses. The web tools STRING, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneCodis, and Ensembl Variant Effect Predictor were used for functional analysis.
    Results: Of the 48 patients with HNC with post-RT PD progression, 24 had no tooth with 5 mm or greater pocket depth before RT, whereas of the 21 patients with HNC without progression, 11 had PD initially. A total of 330 SNPs (249 genes) with over-represented homozygous genotype (98.5% variant allele) were found to be associated with post-RT PD. Sixty of these corresponded to PD-related pathways, including previously identified genes. In patients with HNC with post-RT PD progression, SNPs were found in genes (n = 10) in contrast to those without progression (n = 7).
    Conclusions: The SNPs of collagen genes were identified, potentially defining susceptibility to PD in patients with HNC, and this could be further investigated to characterize PD drug targets.
    MeSH term(s) Exome ; Head and Neck Neoplasms ; Humans ; Nucleotides ; Periodontal Diseases ; Polymorphism, Single Nucleotide
    Chemical Substances Nucleotides
    Language English
    Publishing date 2020-05-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2650843-6
    ISSN 2212-4411 ; 2212-4403
    ISSN (online) 2212-4411
    ISSN 2212-4403
    DOI 10.1016/j.oooo.2020.02.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Variation of Serum Lycopene in Response to 100% Watermelon Juice: An Exploratory Analysis of Genetic Variants in a Randomized Controlled Crossover Study.

    Crowe-White, Kristi M / Voruganti, Venkata S / Talevi, Valentina / Dudenbostel, Tanja / Nagabooshanam, Vinoth A / Locher, Julie L / Ellis, Amy C

    Current developments in nutrition

    2020  Volume 4, Issue 7, Page(s) nzaa102

    Abstract: Background: Watermelon, a rich source of lycopene, has garnered attention for cardioprotective effects including cholesterol reduction and promotion of redox balance. It is unknown whether 100% watermelon juice may represent a food-first approach to ... ...

    Abstract Background: Watermelon, a rich source of lycopene, has garnered attention for cardioprotective effects including cholesterol reduction and promotion of redox balance. It is unknown whether 100% watermelon juice may represent a food-first approach to confer cardioprotective benefits of lycopene.
    Objectives: This study examined influences of 100% watermelon juice on serum lycopene, lipids, and antioxidant capacity. Secondly, the study explored genetic influences on lycopene metabolism and bioavailability.
    Methods: A placebo-controlled, randomized, double-blind, crossover trial with postmenopausal women (
    Results: Serum lycopene exhibited a significant treatment effect (
    Conclusions: Watermelon juice supplementation did not result in improvements in serum lipids or antioxidant capacity; however, results support findings in which watermelon juice significantly, yet differentially, increased circulating lycopene. Genetics appears to explain some of the variability. Given that dose has been shown to overcome individual responsiveness to lycopene interventions, future investigations with varying doses of lycopene-rich foods would be strengthened by genotyping so as to establish personalized nutrition recommendations.This trial was registered at clinicaltrials.gov as NCT03626168.
    Language English
    Publishing date 2020-06-17
    Publishing country United States
    Document type Journal Article
    ISSN 2475-2991
    ISSN (online) 2475-2991
    DOI 10.1093/cdn/nzaa102
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  4. Article ; Online: Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.

    Aschenbrenner, Anna C / Mouktaroudi, Maria / Krämer, Benjamin / Oestreich, Marie / Antonakos, Nikolaos / Nuesch-Germano, Melanie / Gkizeli, Konstantina / Bonaguro, Lorenzo / Reusch, Nico / Baßler, Kevin / Saridaki, Maria / Knoll, Rainer / Pecht, Tal / Kapellos, Theodore S / Doulou, Sarandia / Kröger, Charlotte / Herbert, Miriam / Holsten, Lisa / Horne, Arik /
    Gemünd, Ioanna D / Rovina, Nikoletta / Agrawal, Shobhit / Dahm, Kilian / van Uelft, Martina / Drews, Anna / Lenkeit, Lena / Bruse, Niklas / Gerretsen, Jelle / Gierlich, Jannik / Becker, Matthias / Händler, Kristian / Kraut, Michael / Theis, Heidi / Mengiste, Simachew / De Domenico, Elena / Schulte-Schrepping, Jonas / Seep, Lea / Raabe, Jan / Hoffmeister, Christoph / ToVinh, Michael / Keitel, Verena / Rieke, Gereon / Talevi, Valentina / Skowasch, Dirk / Aziz, N Ahmad / Pickkers, Peter / van de Veerdonk, Frank L / Netea, Mihai G / Schultze, Joachim L / Kox, Matthijs / Breteler, Monique M B / Nattermann, Jacob / Koutsoukou, Antonia / Giamarellos-Bourboulis, Evangelos J / Ulas, Thomas

    Genome medicine

    2021  Volume 13, Issue 1, Page(s) 7

    Abstract: Background: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress ... ...

    Abstract Background: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system.
    Methods: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings.
    Results: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.
    Conclusions: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.
    MeSH term(s) Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/pathology ; COVID-19/virology ; Case-Control Studies ; Down-Regulation ; Drug Repositioning ; Humans ; Neutrophils/cytology ; Neutrophils/immunology ; Neutrophils/metabolism ; Phenotype ; Principal Component Analysis ; RNA/blood ; RNA/chemistry ; RNA/metabolism ; Sequence Analysis, RNA ; Severity of Illness Index ; Transcriptome ; Up-Regulation
    Chemical Substances Antiviral Agents ; RNA (63231-63-0)
    Language English
    Publishing date 2021-01-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-020-00823-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

    Ulas, Thomas / Seep, Lea / Schulte-Schrepping, Jona / De Domenico, Elena / Mengiste, Simachew / Theis, Heidi / Kraut, Michael / Becker, Matthias / Gierlich, Jannik / Lenkeit, Lena / Drews, Anna / van Uelft, Martina / Dahm, Kilian / Agrawal, Shobhit / Gemuend, Ioanna D / Horne, Arik / Holsten, Lisa / Herbert, Miriam / Kroeger, Charlotte /
    Kapellos, Theodorw S / Pecht, Tal / Knoll, Rainer / Bassler, Kevin / Reusch, Nico / Bonaguro, Lorenzo / Nuesch-Germano, Melanie / Oestreich, Marie / Aschenbrenner, Anna Christin / Schultze, Joachim L / Kox, Matthijs / Bruse, Niklas / Pickkers, Peter / Gerretsen, Jelle / Netea, Mihai. G / van de Veerdonk, Frank / Nattermann, Jacob / Kraemer, Benjamin / Raabe, Jan / ToVinh, Michael / Hoffmeister, Christoph / Rieke, Gereon J / Keitel, Verena / Breteler, Monique MB / Aziz, Ahmad N / Talevi, Valentina / Giamarellos-Bourboulis, Evangelos J / Mouktaroudi, Maria / Antonakos, Nikolaos / Gkizeli, Konstantina / Saridaki, Maria / Doulou, Sarantia / Rovina, Nikoletta / Koutsoukou, Antonia

    medRxiv

    Abstract: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, ... ...

    Abstract The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,600 samples derived from 11 different viral infections, inflammatory diseases and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.
    Keywords covid19
    Language English
    Publishing date 2020-07-08
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.07.07.20148395
    Database COVID19

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