Hyper-inflammatory responses can lead to a variety of diseases including sepsis. It is now shown that extracellular histones released in response to inflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death during sepsis. As such, they can be targeted pharmacologically by inhibitors, as well as used as biomarkers for prognosis of sepsis and other diseases.

Compositions and methods for therapeutic delivery are disclosed. More particularly, the present disclosure relates to nanoparticle compositions that sequester the activity of a target molecule while leaving other domains accessible to bind targeted tissues of interest. Methods for thrombus dissolution include administering a nanoparticle reversibly coupled to a target molecule that can dissolve a blood clot. Compositions and methods for inducing blood clotting are also disclosed. Methods for inducing blood clotting include administering a nanoparticle reversibly coupled to a target molecule that can induce the formation of a blood clot. Methods for sequestering a target molecule are also disclosed. The method includes reversibly coupling a target molecule to a nanoparticle having an affinity ligand that reversibly couples the target molecule, and thus, sequesters the target molecule activity until the target molecule interacts with its substrate resulting in the release of the target molecule.

A method of treating or preventing adverse outcomes associated with tissue plasminogen activator (tPA) administration, cerebral edema-related side effects, cerebral edema associated with radiation therapy, or migraine headaches by administering an effective amount of a SUR1-TRPM4 channel inhibitor, such as glyburide, and optionally the co-administration of a second therapeutically active agent, to a subject in need thereof. Adverse outcomes associated with tPA include cerebral hemorrhage, cerebral edema, physical impairment or death. The administration of the SUR1-TRPM4 channel inhibitors occurs prior to the radiation therapy, during the radiation therapy, after the radiation therapy, or combinations thereof. The SUR1-TRPM4 channel inhibitor is administered prior to surgical excision of a brain tumor, CAR-T therapy, or administration of flutarabine. Alternatively, or in addition, the SUR1-TRPM4 channel inhibitor is administered prior the onset of the cerebral edema-related side effects.

Materials and methods of in vivo possessing of target proteins in plants by co-expressing with proprotein processing enzyme, human Furin, are provided. A method of expressing highly soluble and functional active human Furin in plants also is provided.

To provide a method for producing a horseshoe crab recombinant Factor C. The horseshoe crab recombinant Factor C is produced through expression thereof by use of mammalian cells such as CHO DG44 and HEK293 as host cells.

Compositions and methods for regulating the blood coagulation pathway are disclosed. More particularly, the present disclosure relates to thrombin-thrombomodulin fusion proteins, vectors, host cells and methods for preparing the thrombin-thrombomodulin fusion proteins. The present disclosure further relates to methods for measuring protein C in plasma and kits for measuring protein C in plasma.

Use of activated protein C (APC) for treatment and prevention of ocular diseases, disorders or conditions associated with retinal leakage and CNV such as age-related macular degeneration, optionally in combined therapy with anti-angiogenesis, anti-inflammatory, immunosuppressive, and anti PDGF agent.

Methods for treating and/or preventing choroidal neovascularization (CNV) or retinal leakage associated with CNV are disclosed, comprising the use of activated protein C (APC) and/or an APC variant. A disclosed method may be applied in the treatment or prevention of ocular diseases, disorders or conditions that are caused directly by CVN, feature development of CNV as a secondary stage or a complication thereof, and/or feature CNV as a synchronous or asynchronous sequela thereof. An exemplary disease treatable by a disclosed method is neovascular age-related macular degeneration (nAMD).

This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences T cell balance, for example, Th17 cell differentiation, maintenance and/or function, as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences T cell balance in a variety of therapeutic and/or diagnostic indications. This invention also relates generally to identifying and exploiting target genes and/or target gene products that modulate, control or otherwise influence T cell balance in a variety of therapeutic and/or diagnostic indications.

The invention relates to methods of using an effective amount of activated protein C (APC) to treat an individual for a skin disorder characterised by the presence of hyperproliferative keratinocytes.