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2. Serum metabolome associated with severity of acute traumatic brain injury

Author

Thomas, Ilias, Dickens, Alex M., Posti, Jussi P., Czeiter, Endre, Duberg, Daniel, Sinioja, Tim, Kråkström, Matilda, Retel Helmrich, Isabel R. A., Wang, Kevin K. W., Maas, Andrew I. R., Steyerberg, Ewout W., Menon, David K., Tenovuo, Olli, Hyötyläinen, Tuulia, Büki, András, Orešič, Matej, Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny Gabriele Wagner, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Røe, Cecilie, Røise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Te Ao, Braden, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Åkerlund, Cecilia, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Amrein, Krisztina, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Andelic, Nada, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Andreassen, Lasse, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Anke, Audny, Te Ao, Braden, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Antoni, Anna, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Audibert, Gérard, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Azouvi, Philippe, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Azzolini, Maria Luisa, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Molecular Neuroscience and Ageing Research (MOLAR), Psychology 3, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Posti, Jussi P [0000-0002-5925-5193], Czeiter, Endre [0000-0002-9578-6944], Maas, Andrew IR [0000-0003-1612-1264], Steyerberg, Ewout W [0000-0002-7787-0122], Menon, David [0000-0002-3228-9692], Orešič, Matej [0000-0002-2856-9165], Apollo - University of Cambridge Repository, CENTER-TBI Participants Investigators, Menon, David K [0000-0002-3228-9692], Public Health, Neurology, Neurosurgery, Intensive Care, Pediatric Surgery, Thomas, I, Dickens, A, Posti, J, Czeiter, E, Duberg, D, Sinioja, T, Kråkström, M, Retel Helmrich, I, Wang, K, Maas, A, Steyerberg, E, Menon, D, Citerio, G, „Springer Nature' grupė, Ročka, Saulius, and Tamošuitis, Tomas

Subjects
Traumatic, IMPACT, BIOMARKERS, General Physics and Astronomy, acute traumatic brain injury, General Biochemistry, Genetics and Molecular Biology, CHAIN AMINO-ACIDS, MYOINOSITOL, Cohort Studies, GLUTAMATE, 692/53, Brain Injuries, Traumatic, Metabolomics/methods, TOOL, Humans, Metabolomics, Serum metabolome, 692/699/375/1345, 631/378/1689, OUTCOMES, Multidisciplinary, article, General Chemistry, MAGNETIC-RESONANCE-SPECTROSCOPY, 140/58, nervous system diseases, nervous system, Brain Injuries, Metabolome, MODERATE, CHOLINE, Human medicine
Abstract

Nature Communications 13, 2545 (2022). doi:10.1038/s41467-022-30227-5, Published by Nature Publishing Group UK, [London]

Published
2022

3. Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity.

Author

Lanzon, Borja, Martin-Taboada, Marina, Castro-Alves, Victor, Vila-Bedmar, Rocio, González de Pablos, Ignacio, Duberg, Daniel, Gomez, Pilar, Rodriguez, Elias, Orešič, Matej, Hyötyläinen, Tuulia, Morales, Enrique, Ruperez, Francisco J., and Medina-Gomez, Gema

Subjects
CHRONIC kidney failure, CHRONICALLY ill, LIQUID chromatography-mass spectrometry, DISEASE risk factors, HIPPURIC acid, GLUTAMINE
Abstract

Severe obesity is a major risk for chronic kidney disease (CKD). Early detection and careful monitoring of renal function are critical for the prevention of CKD during obesity, since biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of clinical parameters. To explore whether distinct lipid and metabolic signatures in obesity may signify early stages of pathogenesis toward CKD, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) analyses were performed in the serum and the urine of severely obese patients with and without CKD. Moreover, the impact of bariatric surgery (BS) in lipid and metabolic signature was also studied, through LC-MS and GC-HRAM-MS analyses in the serum and urine of patients with severe obesity and CKD before and after undergoing BS. Regarding patients with severe obesity and CKD compared to severely obese patients without CKD, serum lipidome analysis revealed significant differences in lipid signature. Furthermore, serum metabolomics profile revealed significant changes in specific amino acids, with isoleucine and tyrosine, increased in CKD patients compared with patients without CKD. LC-MS and GC-HRAM-MS analysis in serum of patients with severe obesity and CKD after BS showed downregulation of levels of triglycerides (TGs) and diglycerides (DGs) as well as a decrease in branched-chain amino acid (BCAA), lysine, threonine, proline, and serine. In addition, BS removed most of the correlations in CKD patients against biochemical parameters related to kidney dysfunction. Concerning urine analysis, hippuric acid, valine and glutamine were significantly decreased in urine from CKD patients after surgery. Interestingly, bariatric surgery did not restore all the lipid species, some of them decreased, hence drawing attention to them as potential targets for early diagnosis or therapeutic intervention. Results obtained in this study would justify the use of comprehensive mass spectrometry-based lipidomics to measure other lipids aside from conventional lipid profiles and to validate possible early markers of risk of CKD in patients with severe obesity. [ABSTRACT FROM AUTHOR]

Published
2021
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4. Metabolic and phenotypic changes induced by PFAS exposure in two human hepatocyte cell models.

Author

Alijagic, Andi, Sinisalu, Lisanna, Duberg, Daniel, Kotlyar, Oleksandr, Scherbak, Nikolai, Engwall, Magnus, Orešič, Matej, and Hyötyläinen, Tuulia

Subjects
*FREE fatty acids, *GOLGI apparatus, *PHENOTYPIC plasticity, *FLUOROALKYL compounds, *CELL morphology
Abstract

[Display omitted] • PFAS causes dose-dependent, non-monotonic responses on multiple metabolites. • PFAS exposure is linked with changes in bile acid and glucose metabolism. • PFAS exposure is linked with oxidative stress and inflammatory response. • PFAS exposure has impacts on cell morphology. PFAS are ubiquitous industrial chemicals with known adverse health effects, particularly on the liver. The liver, being a vital metabolic organ, is susceptible to PFAS-induced metabolic dysregulation, leading to conditions such as hepatotoxicity and metabolic disturbances. In this study, we investigated the phenotypic and metabolic responses of PFAS exposure using two hepatocyte models, HepG2 (male cell line) and HepaRG (female cell line), aiming to define phenotypic alterations, and metabolic disturbances at the metabolite and pathway levels. The PFAS mixture composition was selected based on epidemiological data, covering a broad concentration spectrum observed in diverse human populations. Phenotypic profiling by Cell Painting assay disclosed predominant effects of PFAS exposure on mitochondrial structure and function in both cell models as well as effects on F-actin, Golgi apparatus, and plasma membrane-associated measures. We employed comprehensive metabolic characterization using liquid chromatography combined with high-resolution mass spectrometry (LC-HRMS). We observed dose-dependent changes in the metabolic profiles, particularly in lipid, steroid, amino acid and sugar and carbohydrate metabolism in both cells as well as in cell media, with HepaRG cell line showing a stronger metabolic response. In cells, most of the bile acids, acylcarnitines and free fatty acids showed downregulation, while medium-chain fatty acids and carnosine were upregulated, while the cell media showed different response especially in relation to the bile acids in HepaRG cell media. Importantly, we observed also nonmonotonic response for several phenotypic features and metabolites. On the pathway level, PFAS exposure was also associated with pathways indicating oxidative stress and inflammatory responses. Taken together, our findings on PFAS-induced phenotypic and metabolic disruptions in hepatocytes shed light on potential mechanisms contributing to the broader comprehension of PFAS-related health risks. [ABSTRACT FROM AUTHOR]

Published
2024
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