The present invention aims to present methods to detect nonalcoholic fatty liver disease including nonalcoholic steatohepatitis by using a protein or its partial peptide that differs in presence or absence, or in quantity between healthy human subjects and patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis or between patients with fatty liver and nonalcoholic steatohepatitis and further aims to present biomarkers comprising said protein and said partial peptide to be used to detect nonalcoholic fatty liver disease including nonalcoholic steatohepatitis. Specifically, 35 kDa protein fragment consisting of amino acid sequence expressed by Sequence No. 2 and its partial peptide consisting of amino acid sequence expressed by Sequence No. 3 (including its glycated form) of inter-alpha-trypsin inhibitor heavy chain H4 precursor consisting of amino acid sequence expressed by Sequence No. 1 could be used as biomarkers to detect nonalcoholic fatty liver disease including nonalcoholic steatohepatitis.

Provided are: a novel marker useful for measuring hypoxia or predicting the risk of exacerbation of a hypoxia-related pathological condition; a hypoxia measurement method or a method for predicting the risk of exacerbation of a pathological condition using the marker as an indicator; a composition for measuring hypoxia or predicting the risk of exacerbation of a pathological condition; a method for screening a candidate substance for a therapeutic agent for a hypoxia-related pathological condition; a composition for ameliorating a hypoxia-related pathological condition; and the like. A method for measuring hypoxia in a subject or a method for predicting the risk of exacerbation of a pathological condition, each method comprising the step of measuring the amount of SPINK1 in a sample collected from a subject. Use of SPINK1 as a biomarker for measuring hypoxia or for predicting the risk of exacerbation of a pathological condition. A composition for measuring hypoxia or predicting the risk of exacerbation of a pathological condition, the composition comprising a SPINK1 detection reagent. A method for screening a candidate substance for a therapeutic agent for a hypoxia-related pathological condition, the screening being performed by using, as an indicator, whether or not the candidate substance can inhibit SPINK1. A composition for ameliorating a hypoxia-related pathological condition, the composition comprising a SPINK1 inhibitor.

The invention relates to methods of diagnosing, prognosing, or monitoring or staging the progression of non-alcoholic fatty liver disease (NAFLD) using biomarkers. The invention also relates to a method of scoring to determine the severity of NAFLD, and a method of treating NAFLD.

The invention provides compositions and methods for utilizing human epididymal secretion protein E4 (HE4) in the prevention and treatment of cancer and other human diseases.

A method for predicting the degree of weight loss in a female subject attainable by applying one or more dietary interventions to a subject, said method comprising; determining the level of one or more biomarkers in one or more samples obtained from the subject, wherein the biomarkers are selected from gelsolin, apolipoprotein B-100, plasma kallikrein, protein Z-dependent protease inhibitor and plasma serine protease inhibitor.

The present invention relates to a bicyclic inhibitor of the coagulation enzyme activated factor XII (FXIIa) comprising or consisting of the peptide) (X.sup.1)(X.sup.2)(X.sup.3).sub.n(X.sup.4)RL(X.sup.5)(X.sup.6).sub.m(X.sup.7)(X.sup.9).sub.l(X.sup.10)(X.sup.11)(X.sup.12)(X.sup.13)(X.sup.14).sub.k(X.sup.15)(X.sup.16), wherein (X.sup.1) is present or absent and, if present, is an amino acid; (X.sup.2) is an amino acid with a side chain; (X.sup.3) is an amino acid and n is between 0 and 3, preferably 0 or 1 and most preferably 0; (X.sup.4) is an aliphatic L-amino acid or a cyclic L-amino acid, preferably L, P or an aromatic L-amino acid, and most preferably an aromatic L-amino acid; (X.sup.5) is an amino acid; (X.sup.6) is an amino acid and m is between 0 and 3, preferably 0 or 1 and most preferably 0; (X.sup.7) is an amino acid with a side chain; (X.sup.9) is an amino acid and l is between 0 and 3, preferably 0 or 1 and most preferably 0; (X.sup.10) is an amino acid; (X.sup.11) is an amino acid, preferably Q; (X.sup.12) is a hydrophobic L-amino acid, preferably an aliphatic L-amino acid, and is most preferably L; (X.sup.13) is an amino acid; (X.sup.14) is an amino acid and k is between 0 and 3, preferably 0 or 1 and most preferably 0, (X.sup.15) is an amino acid with a side chain; and (X.sup.16) is present or absent and, if present, is an amino acid; and wherein the side chains of (X.sup.2), (X.sup.7) and (X.sup.15) are connected via a connecting molecule, said connecting molecule having at least three functional groups, each functional group forming a covalent bond with one of the side chains of (X.sup.2), (X.sup.7) and (X.sup.15).

This invention relates to a method of predicting progression of an inflammatory condition in a subject, which involves providing a medium comprising hyaluronan or a fragment thereof; contacting the medium with a fluid sample from a subject with an inflammatory condition, where the fluid sample comprises proteins or proteoglycans and a transfer agent; incubating the fluid sample with the medium under conditions effective for the transfer agent in the fluid sample to mediate transfer of heavy chains from the proteins or proteoglycans to the hyaluronan or a fragment thereof to form a complex; detecting, using an antibody, occurrence levels of the complex; and comparing occurrence levels of the complex from said detecting to a reference standard to predict progression of an inflammatory condition in the subject. Also disclosed are methods of tailoring treatment of an inflammatory condition and quantifying local inflammatory activity in a body fluid.

The present invention relates to a method for detecting at least one direct factor Xa inhibitor in a sample other than citrate plasma, comprising the step of mixing a sample containing a factor Xa inhibitor with a composition containing factor Xa under conditions which allow the factor Xa to release a detectable substance from a chromogenic substrate.

The present invention relates to a method for the in vitro diagnosis of colorectal cancer by determining the presence of the Leukocyte Elastase Inhibitor tumor marker in a biological sample taken from a patient suspected of having colorectal cancer. Said method can be used for early diagnosis, screening, therapeutic follow-up and prognosis, and also for relapse diagnosis in relation to colorectal cancer.

A2M polypeptide compositions containing a non-natural bait region are disclosed. Methods of producing wild-type and variant A2M polypeptides and polynucleotides containing a non-natural bait region are also disclosed. The bait regions of the variant A2M polypeptides demonstrate enhanced protease inhibitory characteristics compared to wild-type A2M. Variant A2M polypeptides that demonstrate longer half-lives upon administration to an organism compared to wild-type A2M are disclosed. The A2M compositions are useful in treating a number of diseases and conditions including inflammation, chronic wounds, and diseases with a pathology associated with proteases.