NMR Metabolic Profiling of Mosquito Species to Understand Insecticide Resistance

Grosman, Rudi

doi:10.17638/03067218

Cited by 2 publications

(4 citation statements)

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“…Neutrophil metabolites annotated included amino acids, ketone bodies and several glycolytic intermediates as well as other metabolites. A representative bin for each metabolite was selected using in-house criteria determined by correlation reliability score [ 28 ] and used to perform statistical analysis ( Supplementary Table S1 ). All metabolite annotation and identities are available via public repository MetaboLights (ID number: MTBLS4766).…”

Section: Resultsmentioning

confidence: 99%

“…All peaks, both annotated in Chenomx (via manual analyses in TopSpin and Chenomx software) and unknown, were included in the bin table. A correlation-based scoring (CRS) method developed by Grosman [ 28 ] was applied to the data which aimed at addressing the problem of selecting appropriate representative bins from feature extraction in multivariate analysis. A list of representative bins per metabolite identified was obtained ( Supplementary Table S1 ), and statistical analysis was carried out.…”

Section: Methodsmentioning

confidence: 99%

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Metabolic Profiling of Rheumatoid Arthritis Neutrophils Reveals Altered Energy Metabolism That Is Not Affected by JAK Inhibition

et al. 2022

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Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function can be modulated by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However, clinical trials have reported increased infection rates and transient neutropenia during therapy. The subtle differences in the mode of action, efficacy and safety of JAK inhibitors have been the primary research topic of many clinical trials and systematic reviews, to provide a more precise and targeted treatment to patients. The aim of this study was to determine both the differences in the metabolome of neutrophils from healthy controls and people with RA, and the effect of different JAK inhibitors on the metabolome of healthy and RA neutrophils. Isolated neutrophils from healthy controls (HC) (n = 6) and people with RA (n = 7) were incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200 ng/mL) for 2 h. Metabolites were extracted, and 1H nuclear magnetic resonance (NMR) was applied to study the metabolic changes. Multivariate analyses and machine learning models showed a divergent metabolic pattern in RA neutrophils compared to HC at 0 h (F1 score = 86.7%) driven by energy metabolites (ATP, ADP, GTP and glucose). No difference was observed in the neutrophil metabolome when treated with JAK inhibitors. However, JAK inhibitors significantly inhibited ROS production and baricitinib decreased NET production (p < 0.05). Bacterial killing was not impaired by JAK inhibitors, indicating that the effect of JAK inhibitors on neutrophils can inhibit joint damage in RA without impairing host defence. This study highlights altered energy metabolism in RA neutrophils which may explain the cause of their dysregulation in inflammatory disease.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Metabolic Profiling of Rheumatoid Arthritis Neutrophils Reveals Altered Energy Metabolism That Is Not Affected by JAK Inhibition

et al. 2022

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“…Neutrophil metabolites annotated included amino acids, ketone bodies and several glycolytic intermediates as well as other metabolites. A representative bin for each metabolite was selected using in-house criteria determined by correlation reliability score [28] and used to perform statistical analysis (Supplementary Table 1). All metabolite annotation and identities are available via public repository MetaboLights (ID number: MTBLS4766).…”

Section: Resultsmentioning

confidence: 99%

“…All spectra passing quality criteria were then divided into "bins" that were defined globally by the peak limits using Chenomx NMR Suite 7.1 (Chenomx Inc., Edmonton, Alberta, Canada) [27]. All peaks, both annotated in Chenomx (via manual analyses in TopSpin and Chenomx software) and unknown, were included in the bin table . A correlation-based scoring (CRS) method developed by Grosman [28] was applied to the data which aimed at addressing the problem of selecting appropriate representative bins from feature extraction in multivariate analysis. A list of representative bins per metabolite identified was obtained (Supplementary Table 1) and statistical analysis was carried out.…”

Section: H-nmr Measurementsmentioning

confidence: 99%

Metabolic profiling of rheumatoid arthritis neutrophils reveals altered energy metabolism that is not affected by JAK inhibition

Chokesuwattanaskul

Alarcon

Mangalakumaran

et al. 2022

Preprint

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Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function can be modulated by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However clinical trials have reported increased infection rates and transient neutropenia during therapy. The subtle differences in the mode of action, efficacy and safety of JAK inhibitors has been the primary research topic of many clinical trials and systematic reviews, to provide a more precise and targeted treatment to patients. The aim of this study was to determine both the differences in the metabolome of neutrophils from healthy controls and people with RA, and the effect of different JAK inhibitors on the metabolome of healthy and RA neutrophils. Isolated neutrophils from healthy controls (HC) (n=6) and people with RA (n=7) were incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200ng/mL) for 2h. Metabolites were extracted and 1H nuclear magnetic resonance (NMR) was applied to study the metabolic changes. Multivariate analyses and machine learning models showed a divergent metabolic pattern in RA neutrophils compared to HC at 0h (F1 score = 86.7%) driven by energy metabolites (ATP, ADP, GTP and glucose). No difference was observed in the neutrophil metabolome when treated with JAK inhibitors. However, JAK inhibitors significantly inhibited ROS production and baricitinib decreased NET production (p<0.05). Bacterial killing was not impaired by JAK inhibitors, indicating the effect of JAK inhibitors on neutrophils can inhibit joint damage in RA without impairing host defence. This study highlights altered energy metabolism in RA neutrophils which may explain the cause of their dysregulation in inflammatory disease.

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NMR Metabolic Profiling of Mosquito Species to Understand Insecticide Resistance

Cited by 2 publications

References 0 publications

Metabolic Profiling of Rheumatoid Arthritis Neutrophils Reveals Altered Energy Metabolism That Is Not Affected by JAK Inhibition

Metabolic Profiling of Rheumatoid Arthritis Neutrophils Reveals Altered Energy Metabolism That Is Not Affected by JAK Inhibition

Metabolic profiling of rheumatoid arthritis neutrophils reveals altered energy metabolism that is not affected by JAK inhibition

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