The present application provides compositions and methods for determining a disease or condition in a subject. The method comprises contacting a body fluid with a molecule comprising a reporter thereof and the reported is cleaved by an agent in the body fluid. Diseases and conditions that can be determined by the method are also described.

A method for predicting sepsis or diagnosing systemic inflammatory response syndrome (SIRS) and/or sepsis in a subject comprises determining levels of at least three markers selected from CCL23, A1AT, CRP, sICAM, PLA2, IL-6, procalcitonin, MMP8, TNFalpha, AcPGP, enzymatic MMP activity, TIMP1, sRAGE and desmosine in a sample taken from the subject. The combined levels of the at least three markers are used to predict or diagnose SIRS and/or sepsis. The methods may be performed on a subject with SIRS and which is used to identify an infection in the subject. A preferred panel of markers includes CCL23, A1AT, sICAM, sICAM/VCAM-1 and CRP. Corresponding products, methods of treatment and medical uses are provided.

Provided herein are methods and compositions for treating a coronavirus disease, and particularly its complications, in a subject infected with a pathogenic coronavirus, such as a subject infected with a SARS-CoV-2 or suffering from one or more signs or symptoms of COVID-19. The composition comprises a therapeutically effective amount of an isolated or recombinant disintegrin and metalloproteinase with a thrombospondin type 1 motif (ADAMTS13) protein. The present disclosure further relates to methods for diagnosing a coagulopathy in subject infected with a coronavirus disease, particularly SARS-CoV-2, or suffering from one or more signs or symptoms of COVID-19. The method comprises testing for elevated levels of VWF, depressed levels of ADAMTS13, and the presence of UHMW VWF multimers. These factors, in combination, indicate the presence of a coagulopathy.

The present application provides compositions and methods for determining a disease or condition in a subject. The method comprises contacting a body fluid with a molecule comprising a reporter thereof and the reported is cleaved by an agent in the body fluid. Diseases and conditions that can be determined by the method are also described.

The present invention provides compositions and methods useful for regulating fertilization and for use as a contraceptive based on the discovery herein of an oocyte specific protein, SAS1R (Sperm Acrosomal SLLP1 Receptor), which is a sperm protein receptor. Six SAS1R variants, including the full length SAS1R, were identified. mSLLP1 and SAS1R co-localized to oocytes and to acrosomes of acrosome-reacted sperm. Interactions between mSLLP1 and SAS1R were demonstrated by far-western analysis, in a yeast two-hybrid system under stringent selection conditions, and by immunoprecipitation of SAS1R by anti-mSLLP1 as well as the converse. Purified recombinant SAS1R was found to have protease activity, to inhibit fertilization in-vitro, and to induce an immune response in females. Together, the results suggest SAS1R is a proteolytically active, oocyte and early embryo specific oolemmal metalloprotease receptor for the sperm intra-acrosomal ligand SLLP1 and is a target for regulating fertilization and as a contraceptive.

Methods and kits for diagnosing the presence of and prognosing the appearance of tissue remodelling-associated conditions, involving the presence of enzyme complexes in a biological sample, are disclosed. In particular, the method pertains to diagnosing the presence of or prognosing appearance of metastatic cancer by the identification of high molecular weight enzyme complexes comprising MMPs.

The present invention provides MT4-MMP inhibitor and EGFR inhibitor for use in the treatment of cancer, wherein said MT4-MMP inhibitor and EGFR inhibitor are different from each other. MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol (GPI) anchored MMP produced by cancer cells that promotes tumor vascularization and metastases. The present invention found that MT4-MMP expression promotes cancer cell proliferation. These effects involve retinoblastoma protein (Rb) inactivation, cyclin dependent kinase CDK4 activation and Epidermal Growth Factor Receptor (EGFR) signaling. Co-immuno-precipitations indicate the existence of protein complexes harboring MT4-MMP and EGFR. The present invention further found a novel mechanism of MT4-MMP action through an outside-in signaling involving EGFR. An unexpected crosstalk between an MMP and EGFR was identified and recognized as a key driver of cancer cell biology.

The present invention relates to the field of fibrosis and inflammation and more particularly to the use of ADAM12 (A Disintegrin and Metalloproteinase 12) inhibitors to prevent or treat inflammation-induced fibrosis. The present invention also relates to the use of ADAM12 as a marker for inflammation-induced fibrosis and to the ablation of ADAM12 expressing cells as therapeutic approach to interfere with the development of pro-fibrotic cells.

Provided herein is a method of bioassay for the quantification of peptide fragments relevant to neurodegenerative conditions. The method comprises cleaving a Tau protein by a secretase, such as ADAM10, to form a neo-epitope. The method comprises contacting a blood derived sample with an antibody specific for the neo-epitope and determining the level of binding of the antibody to peptide fragments comprising the neo-epitope in the sample. Neo-epitope containing peptide levels are found to be inversely correlated to cognitive function.

A four-biomarker panel for diagnosis of chronic graft-versus-host disease (cGVHD) and methods of prognosing and/or diagnosing cGVHD using the biomarker panel are disclosed.