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Non-alcoholic steatohepatitis (NASH), one of the deleterious stages of non-alcoholic fatty liver disease, remains a significant cause of liver-related morbidity and mortality worldwide. In the current work, we used an exploratory data analysis to investigate time-dependent cellular and mitochondrial effects of different supra-physiological fatty acids (FA) overload strategies, in the presence or absence of fructose (F), on human hepatoma-derived HepG2 cells. We measured intracellular neutral lipid content and reactive oxygen species (ROS) levels, mitochondrial respiration and morphology, and caspases activity and cell death. FA-treatments induced a time-dependent increase in neutral lipid content, which was paralleled by an increase in ROS. Fructose, by itself, did not increase intracellular lipid content nor aggravated the effects of palmitic acid (PA) or free fatty acids mixture (FFA), although it led to an up-expression of hepatic fructokinase. Instead, F decreased mitochondrial phospholipid content, as well as OXPHOS subunits levels. Increased lipid accumulation and ROS in FA-treatments preceded mitochondrial dysfunction, comprising altered mitochondrial membrane potential (ΔΨm) and morphology, and decreased oxygen consumption rates, especially with PA. Consequently, supra-physiological PA alone or combined with F prompted the activation of caspase pathways leading to a time-dependent decrease in cell viability. Exploratory data analysis methods support this conclusion by clearly identifying the effects of FA treatments. In fact, unsupervised learning algorithms created homogeneous and cohesive clusters, with a clear separation between PA and FFA treated samples to identify a minimal subset of critical mitochondrial markers in order to attain a feasible model to predict cell death in NAFLD or for high throughput screening of possible therapeutic agents, with particular focus in measuring mitochondrial function.
Ricardo Amorim; Inês Simões; Caroline Veloso; Adriana Carvalho; Rui Simões; Francisco Pereira; Theresa Thiel; Andrea Normann; Catarina Morais; Amália Jurado; Mariusz Wieckowski; José Teixeira; Paulo Oliveira. Exploratory Data Analysis of Cell and Mitochondrial High-Fat, High-Sugar Toxicity on Human HepG2 Cells. Nutrients 2021, 13, 1723 .
AMA StyleRicardo Amorim, Inês Simões, Caroline Veloso, Adriana Carvalho, Rui Simões, Francisco Pereira, Theresa Thiel, Andrea Normann, Catarina Morais, Amália Jurado, Mariusz Wieckowski, José Teixeira, Paulo Oliveira. Exploratory Data Analysis of Cell and Mitochondrial High-Fat, High-Sugar Toxicity on Human HepG2 Cells. Nutrients. 2021; 13 (5):1723.
Chicago/Turabian StyleRicardo Amorim; Inês Simões; Caroline Veloso; Adriana Carvalho; Rui Simões; Francisco Pereira; Theresa Thiel; Andrea Normann; Catarina Morais; Amália Jurado; Mariusz Wieckowski; José Teixeira; Paulo Oliveira. 2021. "Exploratory Data Analysis of Cell and Mitochondrial High-Fat, High-Sugar Toxicity on Human HepG2 Cells." Nutrients 13, no. 5: 1723.
The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein and the N-protein, as well as the neutralizing activity (NAbs) against SARS-CoV-2 in the blood of moderately afflicted COVID-19 patients, needs further longitudinal investigation. Several new serological methods to examine these parameters were developed, validated and applied in three patients of a family which underwent an ambulatory course of COVID-19 for six months. The virus load had almost completely disappeared after about four weeks. Serum IgA levels to the S1-RBD-protein and, to a lesser extent, to the N-protein, peaked about three weeks after clinical disease onset but declined soon thereafter. IgG levels rose continuously, reaching a plateau at approximately six weeks, and stayed elevated over the observation period. Virus-neutralizing activity reached a peak about 4 weeks after disease onset but dropped slowly. The longitudinal associations of virus neutralization and the serological immune response suggest immunity in patients even after a mild clinical course of COVID-19.
Bertram Flehmig; Michael Schindler; Natalia Ruetalo; Ramona Businger; Manfred Bayer; Angelika Haage; Thomas Kirchner; Karin Klingel; Andrea Normann; Lutz Pridzun; Despina Tougianidou; Michael B. Ranke. Persisting Neutralizing Activity to SARS-CoV-2 over Months in Sera of COVID-19 Patients. Viruses 2020, 12, 1357 .
AMA StyleBertram Flehmig, Michael Schindler, Natalia Ruetalo, Ramona Businger, Manfred Bayer, Angelika Haage, Thomas Kirchner, Karin Klingel, Andrea Normann, Lutz Pridzun, Despina Tougianidou, Michael B. Ranke. Persisting Neutralizing Activity to SARS-CoV-2 over Months in Sera of COVID-19 Patients. Viruses. 2020; 12 (12):1357.
Chicago/Turabian StyleBertram Flehmig; Michael Schindler; Natalia Ruetalo; Ramona Businger; Manfred Bayer; Angelika Haage; Thomas Kirchner; Karin Klingel; Andrea Normann; Lutz Pridzun; Despina Tougianidou; Michael B. Ranke. 2020. "Persisting Neutralizing Activity to SARS-CoV-2 over Months in Sera of COVID-19 Patients." Viruses 12, no. 12: 1357.
Summary Background Patients infected with SARS-CoV-2 exhibit a highly variable clinical course, varying from barely discernible signs of disease, to moderate flu-like symptoms and, occasionally, with life-threatening pneumonia and/or cytokine storm. The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein and the N-protein as well the neutralizing activity (NAbs) against SARS-CoV-2 in the blood of moderately afflicted COVID-19 patients has not been investigated longitudinally so far. Methods Several new serological methods to examine these parameters were developed and validated for the longitudinal investigation in three patients of a family which underwent a mild course of COVID-19. Findings We observed that the virus load had almost completely disappeared after about four weeks, whereas serum antibodies showed a contrasting course. IgA levels to S1-RBD-protein and, to a lesser extent, to the N-protein, peaked about three weeks after clinical disease onset but declined soon thereafter. IgG levels rose continuously, reaching a plateau approximately six weeks after disease onset. NAbs in serum reached a peak about four weeks after disease onset but dropped to a lower level about six weeks later. Interpretation Our data establishes associations of virus neutralization and a serological immune response foremost against Sars-CoV-2 S1-RDB-protein in a longitudinal manner.
Bertram Flehmig; Michael Schindler; Natalia Ruetalo; Ramona Businger; Manfred Bayer; Angelika Haage; Thomas Kirchner; Karin Klingel; Andrea Normann; Lutz Pridzun; Despina Tougianidou; Michael B. Ranke. Longitudinal analysis of virus load, serum antibody levels and virus neutralizing activity in vitro in cases with less severe COVID-19. 2020, 1 .
AMA StyleBertram Flehmig, Michael Schindler, Natalia Ruetalo, Ramona Businger, Manfred Bayer, Angelika Haage, Thomas Kirchner, Karin Klingel, Andrea Normann, Lutz Pridzun, Despina Tougianidou, Michael B. Ranke. Longitudinal analysis of virus load, serum antibody levels and virus neutralizing activity in vitro in cases with less severe COVID-19. . 2020; ():1.
Chicago/Turabian StyleBertram Flehmig; Michael Schindler; Natalia Ruetalo; Ramona Businger; Manfred Bayer; Angelika Haage; Thomas Kirchner; Karin Klingel; Andrea Normann; Lutz Pridzun; Despina Tougianidou; Michael B. Ranke. 2020. "Longitudinal analysis of virus load, serum antibody levels and virus neutralizing activity in vitro in cases with less severe COVID-19." , no. : 1.