Publikasjoner
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Majewska, Marta; Bhatia, Anil; Maździarz, Mateusz A.; Lepiarczyk, Ewa; Lipka, Aleksandra Katarzyna & Wiszpolska, Marta
[Vis alle 12 forfattere av denne artikkelen]
(2026).
Severity-dependent metabolic rewiring in COVID-19 based on untargeted metabolomic profiling of patient plasma.
PLOS ONE.
21(6),
s. 0352437–0352437.
doi:
10.1371/journal.pone.0352437.
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Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a major global health challenge, characterised by a heterogeneous clinical spectrum. While metabolomic studies have identified disruptions in amino acid, lipid, nucleotide, and energy metabolism during COVID-19, these investigations often lack fine-grained clinical stratification. In this study, we performed untargeted metabolomic profiling of plasma from 25 participants, including five healthy controls and twenty COVID-19 patients classified into four severity groups (COV1–COV4) based on pulmonary involvement and the need for respiratory support. Using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), 541 metabolites were detected and analysed across all samples. Principal component analysis revealed a progressive metabolic divergence corresponding to disease severity. Monocarboxylic acid dysregulation was predominant in early to moderate cases (COV1–COV3), whereas severe disease (COV4) demonstrated a shift toward pyrimidine metabolism enrichment, consistent with heightened nucleotide turnover driven by viral replication and immune cell proliferation. Phenylalanine metabolism emerged as a consistently enriched pathway in COV1–COV3, suggesting aromatic amino acid perturbations as early markers of metabolic stress and immune activation. In contrast, pyrimidine pathway activation in COV4 could reflect profound systemic metabolic reprogramming associated with critical illness. These findings provide novel insights into COVID-19 pathophysiology, highlighting stage-specific metabolic signatures and potential biomarkers for disease monitoring. Our results support the concept of metabolomics-guided precision medicine, offering a rationale for targeted therapeutic interventions based on disease stage and metabolic phenotype.
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Haugsten, Helene Rygvold; Lipka, Aleksandra Katarzyna; Kristoffersen, Anne Karin; Enersen, Morten; Nieminen, Anni & Søland, Tine Merete
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(2025).
Metabolic Changes in Oral Fibroblasts After Exposure to Bacterial Extracellular Vesicles From Three Strains of Porphyromonas gingivalis.
Cellular Microbiology.
ISSN 1462-5814.
2025(1).
doi:
10.1155/cmi/7515004.
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Aims
Porphyromonas gingivalis is a keystone pathogen in periodontitis that releases bacterial extracellular vesicles (bEVs) with a content derived from the membrane and cytosol of the bacteria itself. The bEVs are taken up by host tissue cells, such as oral fibroblasts, yet their effects on human cells remain incompletely understood.
Methods
The aim of this study was to investigate the impact of bEVs on human oral fibroblasts. Targeted liquid chromatography–mass spectrometry was used to assess changes in the metabolome of these cells following exposure to bEVs from three strains of P. gingivalis (ATCC 33277, A7A1-28, and W83). Metabolite content of the bEVs from each strain was also characterized.
Result
Metabolomic analyses revealed both common and strain-specific metabolites in the bEVs from these strains. Additionally, pathways mainly associated with amino acid metabolism were enriched for all. Following exposure to bEVs, the fibroblasts exhibited a metabolic shift in energy metabolism. In particular, fibroblasts incubated with bEVs from ATCC 33277 had a unique profile of enriched pathways after 10 min. However, after 24 h, this profile changed and became more similar to the profile in fibroblasts incubated with bEVs from the two more pathogenic strains. Pathway analysis revealed enrichment of glycerophospholipid and butanoate metabolism for fibroblasts exposed to all the bEVs. Additionally, altered sphingolipid metabolism was observed in fibroblasts following exposure to bEVs from ATCC 33277.
Conclusion
Our findings demonstrate that bEVs derived from P. gingivalis strains can induce changes in cellular processes in fibroblasts. This suggests a role of bEVs in the pathogenesis of periodontitis.
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Søland, Tine Merete; Lipka, Aleksandra Katarzyna; Ruus, Ann-Kristin; Molværsmyr, Ann-Kristin; Galtung, Hilde & Haug, Trude Marie
(2024).
Extracellular vesicles from cancer cell lines of different origins drive the phenotype of normal oral fibroblasts in a CAF-like direction.
Frontiers in Oncology.
14.
doi:
10.3389/fonc.2024.1456346.
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Introduction: Normal oral fibroblasts (NOFs) are located in the connective tissue of the oral mucosa. The NOFs play an important role in wound healing, tumor progression, and metastasis. They are subjected to influence by external and internal stimuli, among them extracellular vesicles (EVs), that are considered as important players in cell to cell communication, especially in carcinogenesis and metastatic processes. During tumorigenesis, stromal NOFs may undergo activation into cancer-associated fibroblasts (CAFs) that modify their phenotype to provide pro-oncogenic signals that in turn facilitate tumor initiation, progression, and metastasis. The aim of the study was to reveal the effect of EVs derived from local (oral squamous cell carcinoma – OSCC) and distant (pancreatic adenocarcinoma – PDAC; malignant melanoma brain metastasis – MBM) cancer origin on NOFs and their possible change into a CAF-like direction. Methods: The effect of each of the cancer EV types on NOFs proliferation, viability, and migration was tested. Also, changes in gene expression of the well-established CAF biomarkers ACTA2, FAP, PDGFR, and two putative CAF biomarkers, the Ca2+- activated ion channels ANO1 and KCNMA, were studied. Results: Obtained results indicate that NOFs receive and process signals transmitted by EVs originating from both OSCC, PDAC, and MBM. The fibroblast response was dependent on EV origin and concentration, and duration of EV exposure. Conclusion: The present results indicate that the molecular cargo of the EVs direct NOFs towards a pro-tumorigenic phenotype.
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Jastrzębski, Jan Paweł; Pascarella, Stefano; Lipka, Aleksandra Katarzyna & Dorocki, Sławomir
(2023).
IncRna: The R Package for Optimizing lncRNA Identification Processes.
Journal of Computational Biology.
ISSN 1066-5277.
doi:
10.1089/cmb.2023.0091.
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Wiszpolska, Marta; Lepiarczyk, Ewa; Paukszto, Łukasz; Makowczenko, Karol; Lipka, Aleksandra Katarzyna & Maździarz, Mateusz
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(2023).
A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice.
Frontiers in Molecular Biosciences.
10.
doi:
10.3389/fmolb.2023.1260716.
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Introduction: Bisphenol A (BPA) is a substance belonging to the endocrine-disrupting chemicals, globally used in the production of polycarbonate plastics. It has been found that BPA enhances carcinogenesis, triggers obesity and exerts a pathogenic effect in several disorders, such as type 2 diabetes, asthma, or increased blood pressure. Recent studies have revealed, that BPA has a harmful impact on the kidneys function, therefore, the current research aimed to explore the specific molecular changes triggered in these organs after oral BPA exposure in mice. Materials and Methods: The experiment was carried out on 12 (3-month-old) female mice. Six mice served as controls. The other 6 mice were treated with BPA in the drinking water at a dose of 50 mg/kg b. w. for 3 months. Then animals were euthanized, the kidneys were collected, and extracted RNA was used to perform RNA-seq. Results: Applied multistep bioinformatics revealed 433 differentially expressed genes (DEGs) in the BPA-treated kidneys (232 upregulated and 201 downregulated). Additionally, 95 differentially expressed long-noncoding RNAs (DELs) were revealed in BPA samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that BPA exposure resulted in profound changes in several essential processes, such as oxidative phosphorylation, mitochondrial and ribosome function, or chemical carcinogenesis. Conclusion: The obtained novel results suggest that BPA has a harmful impact on the fundamental processes of the kidney and significantly impairs its function by inducing mitochondrial dysfunction leading to oxidative stress and reactive oxygen species production.
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Wiszpolska, Marta; Lepiarczyk, Ewa; Maździarz, Mateusz; Paukszto, Łukasz; Makowczenko, Karol & Lipka, Aleksandra
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(2023).
The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies.
Cancers.
15(20).
doi:
10.3390/cancers15205014.
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Bisphenol A (BPA) is an environmental toxin widely used in the production of polycarbonate plastics. A correlation exists between BPA tissue contamination and the occurrence of pathological conditions, including cancer. First-passage detoxification of high BPA amounts in the liver promotes hepatotoxicity and morphological alterations of this organ, but there is a lack of knowledge about the molecular mechanisms underlying these phenomena. This prompted us to investigate changes in the liver transcriptomics of 3-month-old female mice exposed to BPA (50 mg/kg) in drinking water for 3 months. Five female mice served as controls. The animals were euthanized, the livers were collected, and RNA was extracted to perform RNA-seq analysis. The multistep transcriptomic bioinformatics revealed 120 differentially expressed genes (DEGs) in the BPA-exposed samples. Gene Ontology (GO) annotations indicated that DEGs have been assigned to many biological processes, including “macromolecule modification” and “protein metabolic process”. Several of the revealed DEGs have been linked to the pathogenesis of severe metabolic liver disorders and malignant tumors, in particular hepatocellular carcinoma. Data from this study suggest that BPA has a significant impact on gene expression in the liver, which is predictive of the carcinogenic potential of this compound in this organ.
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Publisert
20. jan. 2023 11:56
- Sist endret
6. feb. 2023 10:12
