Browsing by Author "Ansone, Laura"

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    Amino acid metabolism is significantly altered at the time of admission in hospital for severe COVID-19 patients: findings from longitudinal targeted metabolomics analysis
    (2021-12-08) Ansone, Laura; Briviba, Monta; Silamikelis, Ivars; Terentjeva, Anna; Pērkons, Ingus; Birzniece, Līga; Rovīte, Vita; Rozentāle, Baiba; Vīksna, Ludmila; Koļesova, Oksana; Kļaviņš, Kristaps; Klovins, Jānis; Rīga Stradiņš University
    The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we suggest that glutamine deprivation may further result in inhibited M2 macrophage polarization as a complementary process, and highlight the contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application. IMPORTANCE Although the host defense mechanisms against SARS-CoV-2 infection are still poorly described, they are of central importance in shaping the course of the disease and the possible outcome. Metabolomic profiling may complement the lacking knowledge of the molecular mechanisms underlying clinical manifestations and pathogenesis of COVID-19. Moreover, early identification of metabolomics-based biomarker signatures is proved to serve as an effective approach for the prediction of disease outcome. Here we provide the list of metabolites describing the severe, acute phase of the infection and bring the evidence of crucial metabolic pathways linked to aggressive immune responses. Finally, we suggest metabolomic phenotyping as a promising method for developing personalized care strategies in COVID-19 patients.
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    Exploring disease-specific metabolite signatures in hereditary angioedema patients
    (2024) Kaņepa, Adīne; Fan, Jingzhi; Rots, Dmitrijs; Vaska, Annija; Ansone, Laura; Briviba, Monta; Klovins, Janis; Kurjāne, Nataļja; Kļaviņš, Kristaps; Rīga Stradiņš University
    Introduction: Hereditary angioedema (HAE) is a rare, life-threatening autosomal dominant genetic disorder caused by a deficient and/or dysfunctional C1 esterase inhibitor (C1-INH) (type 1 and type 2) leading to recurrent episodes of edema. This study aims to explore HAE patients' metabolomic profiles and identify novel potential diagnostic biomarkers for HAE. The study also examined distinguishing HAE from idiopathic angioedema (AE). Methods: Blood plasma samples from 10 HAE (types 1/2) patients, 15 patients with idiopathic AE, and 20 healthy controls were collected in Latvia and analyzed using LC-MS based targeted metabolomics workflow. T-test and fold change calculation were used to identify metabolites with significant differences between diseases and control groups. ROC analysis was performed to evaluate metabolite based classification model. Results: A total of 33 metabolites were detected and quantified. The results showed that isovalerylcarnitine, cystine, and hydroxyproline were the most significantly altered metabolites between the disease and control groups. Aspartic acid was identified as a significant metabolite that could differentiate between HAE and idiopathic AE. The mathematical combination of metabolites (hydroxyproline * cystine)/(creatinine * isovalerylcarnitine) was identified as the diagnosis signature for HAE. Furthermore, glycine/asparagine ratio could differentiate between HAE and idiopathic AE. Conclusion: Our study identified isovalerylcarnitine, cystine, and hydroxyproline as potential biomarkers for HAE diagnosis. Identifying new biomarkers may offer enhanced prospects for accurate, timely, and economical diagnosis of HAE, as well as tailored treatment selection for optimal patient care.
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    First Report on the Latvian SARS-CoV-2 Isolate Genetic Diversity
    (2021) Zrelovs, Nikita; Ustinova, Monta; Silamikelis, Ivars; Birzniece, Liga; Megnis, Kaspars; Rovite, Vita; Freimane, Lauma; Silamikele, Laila; Ansone, Laura; Pjalkovskis, Janis; Fridmanis, Davids; Vilne, Baiba; Priedite, Marta; Caica, Anastasija; Gavars, Mikus; Perminov, Dmitry; Storozenko, Jelena; Savicka, Oksana; Dimina, Elina; Dumpis, Uga; Klovins, Janis; Rīga Stradiņš University
    Remaining a major healthcare concern with nearly 29 million confirmed cases worldwide at the time of writing, novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 920 thousand deaths since its outbreak in China, December 2019. First case of a person testing positive for SARS-CoV-2 infection within the territory of the Republic of Latvia was registered on 2nd of March 2020, 9 days prior to the pandemic declaration by WHO. Since then, more than 277,000 tests were carried out confirming a total of 1,464 cases of coronavirus disease 2019 (COVID-19) in the country as of 12th of September 2020. Rapidly reacting to the spread of the infection, an ongoing sequencing campaign was started mid-March in collaboration with the local testing laboratories, with an ultimate goal in sequencing as much local viral isolates as possible, resulting in first full-length SARS-CoV-2 isolate genome sequences from the Baltics region being made publicly available in early April. With 133 viral isolates representing ~9.1% of the total COVID-19 cases during the "first coronavirus wave" in the country (early March, 2020-mid-September, 2020) being completely sequenced as of today, here, we provide a first report on the genetic diversity of Latvian SARS-CoV-2 isolates.
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    Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals
    (2019-11-01) Ustinova, Monta; Silamikelis, Ivars; Kalnina, Ineta; Ansone, Laura; Rovite, Vita; Elbere, Ilze; Radovica-Spalvina, Ilze; Fridmanis, Davids; Aladyeva, Jekaterina; Konrade, Ilze; Pirags, Valdis; Klovins, Janis; Rīga Stradiņš University
    Metformin is a commonly used antihyperglycaemic agent for the treatment of type 2 diabetes mellitus. Nevertheless, the exact mechanisms of action, underlying the various therapeutic effects of metformin, remain elusive. The goal of this study was to evaluate the alterations in longitudinal whole-blood transcriptome profiles of healthy individuals after a one-week metformin intervention in order to identify the novel molecular targets and further prompt the discovery of predictive biomarkers of metformin response. Next generation sequencing-based transcriptome analysis revealed metformin-induced differential expression of genes involved in intestinal immune network for IgA production and cytokine-cytokine receptor interaction pathways. Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin’s action. In addition to universal effects, 4 clusters of functionally related genes with a subject-specific differential expression were distinguished, including genes relevant to insulin production (HNF1B, HNF1A, HNF4A, GCK, INS, NEUROD1, PAX4, PDX1, ABCC8, KCNJ11) and cholesterol homeostasis (APOB, LDLR, PCSK9). This inter-individual variation of the metformin effect on the transcriptional regulation goes in line with well-known variability of the therapeutic response to the drug.
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    Replication of LZTFL1 Gene Region as a Susceptibility Locus for COVID-19 in Latvian Population
    (2021-10) Rescenko, Raimonds; Peculis, Raitis; Briviba, Monta; Ansone, Laura; Terentjeva, Anna; Litvina, Helena Daiga; Birzniece, Liga; Megnis, Kaspars; Kolesova, Oksana; Rozentale, Baiba; Viksna, Ludmila; Rovite, Vita; Klovins, Janis; Rīga Stradiņš University