The present invention is directed to methods of treatment of airway obstruction associated with fibrin-containing cast formation by administering a fibrinolytic agent.

The present disclosure provides a polypeptide including an anti-fibrin antibody and a serine protease moiety of human tissue plasminogen activator. Methods for treating thrombosis in a subject in need of such treatment using such polypeptide are also disclosed.

Provided herein are methods for safe and effective thrombolysis in therapy for human subjects with symptoms of a potential stroke or acute myocardial infarction (“AMI”) using a sequential administration of a low dose bolus of human tissue plasminogen activator (“tPA”) followed by an infusion of a mutant form of human pro-urokinase (“proUK”).

In one aspect, the invention provides a peptide comprising a chaperone-mediated autophagy (CMA)-targeting signal domain; a protein-binding domain that selectively binds to a target cytosolic protein; and a cell membrane penetrating domain (CMPD). In another aspect, the invention provides methods for reducing the intracellular expression level of an endogenous target protein in vitro and in an animal, wherein the method involves administration of the peptide. Methods are also provided for treating a pathological condition in an animal, the methods comprising administering the peptide to the animal. In one embodiment, the pathological condition is a neurodegenerative disease. In another embodiment of the invention, the target cytosolic protein is death associated protein kinase I and the CMPD is protein transduction domain of the HIV-1 Tat protein.

Some embodiments provide a system for external manipulation of magnetic nanoparticles in vasculature using a remotely placed magnetic field-generating stator. In one aspect, the systems and methods relate to the control of magnetic nanoparticles in a fluid medium using permanent magnet-based or electromagnetic field-generating stator sources. Such a system can be useful for increasing the diffusion of therapeutic agents in a fluid medium, such as a human circulatory system, which can result in substantial clearance of fluid obstructions, such as vascular occlusions, in a circulatory system resulting in increased blood flow.

The present disclosure is directed to the use of perlecan compositions to reduce the risk of mortality in subjects due to neurological injury such as stroke, including large vessel occlusion, and traumatic brain injury. The disclosure is also directed to the use of perlecan compositions to reduce mortality in stroke patients treated with tPA.

A composition for use in diagnostic and therapeutic applications includes a heteromultivalent nanoparticle or microparticle having an outer surface and a plurality of targeting moieties conjugated to the surface of the nanoparticle or microparticle, the targeting moieties includes a first activated platelet targeting moiety and a second activated platelet targeting moiety.

A method of treating a subject suffering from an ischemic disease associated with Ca.sup.2+ overload is provided, the method including administering to the subject an effective amount of an inhibitor of Ataxia telangiectasia and Rad3-related (ATR) kinase. Also provided is a method of treating a subject suffering from acute ischemic stroke, the method including administering to the subject an effective amount of the ATR kinase inhibitor berzosertib.

Provided herein are compositions, systems, kits, and methods for treating a patient with a thromboembolism by administering nanoconjugates comprising nanoparticles encapsulating and/or conjugated to: i) tissue-type plasminogen activator (tPA), and ii) at least one antioxidant enzyme selected from the group consisting of: superoxide dismutase, glutathione peroxidase, glutathione reductase, and a catalase.

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.