The present disclosure provides, among other things, methods and compositions for diagnosing and treating stress-induced injuries, hypoxia in particular. The present invention is based, in part, on the novel discovery that a metabolite, L-2-hydroxyglutarate, and certain enzymes and substrates regulating its metabolism, mediate stress-induced cellular mechanisms. In some embodiments, provided methods and compositions are used to diagnose and treat diseases with hypoxia-induced injuries. In some embodiments, provided methods and compositions are used to modulate cell pluripotency or differentiation in vivo or in vitro.

A method for measuring levels of specific biomarkers in exhaled breath. Specific compounds such as nitric oxide and isoprene can be monitored from a subject's breath. The resultant measurements can provide indications of the subject's medical condition, or response to an applied stress.

The disclosure concerns a method for measuring and reporting vascularity in a biological tissue sample. The method generally includes: within a digital image of a tissue section, (i) identifying endothelial cells, lymphatic cells, or a combination thereof; (ii) mapping one or more proximity regions, each of the proximity regions defining an area between detected vessels and a first distance outwardly therefrom; and (iii) calculating one or more of: a vessel proximity score or a hypoxia score, wherein the vessel proximity score relates a composition of objects within the proximity regions, and wherein the hypoxia score relates a composition of tissue within or outside of the proximity regions, respectively.

Methods of promoting hypoxia or the hypoxia response for the treatment or prevention of mitochondrial dysfunction and oxidative stress disorders are described. Methods for screening for targets of mitochondrial dysfunction and oxidative stress disorders are also described.

Enolase levels are predictive of the probability that a cancer patient will respond favorably to cancer therapy involving administration of hypoxia-activated achiral phosphoramide mustards.

Methods that include determining levels of melatonin pathway agents (melatonin, L-tryptophan, 5-hydroxytryptophan (5-HTP), serotonin, N-acetylserotonin (NAS), and melatonin receptor 1A (MT1)) in Hypoxic-ischemic brain injury in both newborns (HIE) and adults (stroke), and in ALS, and optionally administering these agents to treat these conditions.

An apparatus for measuring levels of specific biomarkers in exhaled breath. Specific compounds such as nitric oxide and isoprene can be monitored from a subject's breath. The resultant measurements can provide indications of the subject's medical condition, or response to an applied stress.

The present invention relates to a set of biomarkers, which can be used to determine the risk of developing hypoxemia for subjects undergoing open heart surgery with the use of cardiopulmonary bypass (CPB).

The present invention relates to the construction of a new hypoxia inducible factor (HIF) responsive reporter gene construct, the genetic constructs and vectors containing the same. Further, the present invention relates to a stable cell line comprising the HIF responsive reporter construct, as well as methods and uses of the inventive constructs and cell lines to identify modulators of HIF activity.

A compound and method for detecting hypoxic cells and tissue are provided. The compound includes a probe selected from the group consisting of a hypoxia sensitive 2-nitroimidazole containing fluorescence imaging probe, a hypoxia sensitive reversible ON-OFF fluorescence imaging probe, a hypoxia sensitive azo-based fluorescence imaging probe, and combinations thereof. The method includes contacting the cells or tissue with the probe of any one of claims 1-13 and detecting fluorescent intensity of the cell or tissue, wherein increased fluorescent intensity indicates that the cells or tissue is hypoxic. Also provided are a method of synthesizing the compound and a method for synthesizing a therapeutic agent including the compound.