Abstract: Method for the detection of a conformational state of a protein being in a complex mixture of further proteins and other biomolecules, wherein the protein has been subjected to a condition inducing a structural change, including: limited proteolysis of the extract mixture under a condition in which the protein is in the original conformational state to be detected leading to a first fragment sample; directly followed by (2) removal of large peptides and proteins or other biomolecules from said first fragment sample to form an enriched fragment sample; (3) analytical analysis of the enriched fragment sample for the determination of fragments characteristic of having been the result of the limited proteolysis of (1) as well as remaining after the removal (2) for the determination of the conformational state of said at least one protein.

Abstract: The present invention derives from the unexpected finding that pyroptosis is a novel biomarker and target for therapy in liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Gasdermin D (GSDMD), caspase 4, caspase 5, or Interleukin 1 alpha (IL-1?) can be detected and quantified in serum or plasma, and used as biomarkers for outcome in liver failure such as acute liver failure (ALF) and ACLF and other diseases involving aberrant pyroptosis. By antagonising GSDMD, caspase 4, caspase 5 or Interleukin 1 alpha (IL-1?) many of the unwanted consequences or symptoms of liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of GSDMD, caspase 4, caspase 5 or IL-1? that may be used in the treatment or prevention of liver failure such as acute liver failure (ALF) and ACLF.

Abstract: The present invention derives from the unexpected finding that pyroptosis is a novel biomarker and target for therapy in liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Gasdermin D (GSDMD), caspase 4, caspase 5, or Interleukin 1 alpha (IL-1?) can be detected and quantified in serum or plasma, and used as biomarkers for outcome in liver failure such as acute liver failure (ALF) and ACLF and other diseases involving aberrant pyroptosis. By antagonising GSDMD, caspase 4, caspase 5 or Interleukin 1 alpha (IL-1?) many of the unwanted consequences or symptoms of liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of GSDMD, caspase 4, caspase 5 or IL-1? that may be used in the treatment or prevention of liver failure such as acute liver failure (ALF) and ACLF.