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Background & Aims Portal hypertension often develops in patients with advanced chronic liver diseases (CLD), especially cirrhosis and is associated with complications of the disease, such as gastrointestinal bleeding and ascites, which account for high mortality rates. The transjugular intrahepatic portosystemic shunt (TIPS) is one of only a few treatment options for portal hypertension aiming at the decrease of portal venous pressure by establishing an artificial passage for blood from the gastrointestinal tract directly to the liver vein. The current study aimed to investigate the molecular composition of plasma samples from patients with portal hypertension to characterize mediators influenced by TIPS intervention and involved in gut-liver crosstalk. Methods The plasma of 23 patients suffering from advanced CLD with portal hypertension was collected from peripheral veins before and after TIPS treatment and was analyzed by liquid chromatography-mass spectrometry (LC-MS) using a non-targeted approach. Substances in the molecular range of 100 to 1,500 (m/z) with concentration differences induced by the TIPS intervention were identified in peripheral blood. The identified mediators were sequenced through MS/MS and analyzed through literature mining to gain an insight into their function. Results Overall, eleven low molecular weight mediators revealed concentration changes triggered by the TIPS intervention. From these, four peptides and six metabolites were significantly decreased after TIPS, whereas one metabolite showed an increase after the medical procedure. Conclusions In conclusion, we identified in this study ten new biomarker candidates for portal hypertension in patients with CLD, with potential involvement in the regulation of pathological gut-liver crosstalk.

Background and Aims Chronic Kidney Disease (CKD) is causing serious cardiovascular diseases. Creatinine quantification and eGFR estimation are suboptimal approaches for the diagnosis of CKD, especially at early stages. Therefore, there is a strong need for identification of mediators for CKD diagnosis and prediction of disease progression. In this study we follow a cohort of renal healthy patients (controls) and CKD patients (cases) for two years, defining three time points (baseline, after 12 months and after 24 months), with the aim of identifying and characterizing mediators of disease which could be an indication for the development and progression of CKD and its outcome. Method By the employment of liquid chromatography-mass spectrometry (LC-MS) we analyzed the plasma samples from the patients and identified the mediators1 : lysine (K), an angio-associated migratory cell protein (AAMP) peptide and an amiloride-sensitive oxidase (AOC1) peptide, which were consistently and differentially expressed in cases and controls at all time points. Correlation analyses between the mediators and clinical markers were performed using the software R-Studio (RStudio Team (2020). RStudio: Integrated Development for R. RStudio, PBC, Boston, MA URL http://www.rstudio.com/). The AAMP peptide was subsequently tested in a fibroblasts cells culture to investigate whether it was an inflammation inducer, its action was investigated at four different concentrations (0.1nM, 1nM, 100nM, 1000nM). Cells were stimulated for 48h and relative expression of two inflammation markers (CCL2 and IL6) was measured through PCR. Results Correlation analyses revealed that the AAMP peptide showed from modest to strong relations with clinical markers such as creatinine, hemoglobin, blood urea nitrogen, homocysteine, fibrinogen and parathyroid hormone. Results showed that the peptide after 48h of stimulation did not cause an increase in the expression of gene CCL2 at any concentration, but caused a strong increase of gene IL6 (interleukin-6), a cytokine promoting inflammation and B cells maturation. Conclusion In conclusion, angio-associated migratory cell peptide, might be involved in CKD by inducing inflammation and driving the development of cardiovascular consequences such as atherosclerosis. Acknowledgments This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 764474.