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Kynurenine pathway alteration in acute pancreatitis and its role as a biomarker of infected necrosis 1 1. Introduction 1 2. Material and methods 2 2.1. Study site and approvals 2 2.2. Patient recruitment and management 2 2.3. Study design and sample collection 3 2.4. Isolation of total RNA and cDNA preparation 3 2.5. Quantification of mRNA expression 4 2.6. Quantification of inflammatory cytokines 4 2.7. Quantitative determination of kynurenine and tryptophan 4 2.8. Measurement of plasma endotoxin 4 2.9. Plasma metabolomics profiling 4 2.10. Statistical analysis 4 3. Results 5 3.1. Patient characteristics 5 3.2. Plasma inflammatory cytokines, endotoxin, and pro-calcitonin in the study groups 5 3.3. Down-regulation of immunosuppression genes in patients with IPN 5 3.4. Correlation of HLA-DR and KMO with markers of inflammation and infection 5 3.5. Altered kynurenine/tryptophan ratio and its correlation in patients with IPN 6 3.6. Plasma metabolomics profile by GC-MS 8 3.7. Potential role of plasma tryptophan as a biomarker of IPN 9 4. Discussion 9 Author's contribution 11 Funding 11 Ethics approval statement 11 Patient consent statement 11 Declaration of competing interest 11 Append

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UND

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nonfiction