The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

A fibrinolytic enzyme from Agrocybe aegerita and a preparation method thereof. The fibrinolytic enzyme from Agrocybe aegerita is composed of two subunits A and B, the molecular weight of the subunit A is 31.4 kDa; the molecular weight of the subunit B is 21.2 kDa; the twelve amino acids sequence of the N-terminal of the subunit A is shown in SEQ ID No. 1; the twelve amino acids sequence of the N-terminal of the subunit B is shown in SEQ ID No. 2. The optimal temperature for the fibrinolytic enzyme from Agrocybe aegerita provided in the invention is 47 C., which can maintain good activity at physiological pH of human. Fe.sup.2+ at different concentrations shows obvious inhibiting effects on the fibrinolytic enzyme from Agrocybe aegerita. The fibrinolytic enzyme from Agrocybe aegerita exhibits good thrombolytic properties, thus providing a research basis for the preparation of thrombolytic drugs and/or functional foods.

Pharmaceutical compositions comprising plasminogen or a biologically active variant thereof are disclosed. In an embodiment, the composition comprises a tonicity modifier, a bulking agent, and a stabilising agent and has a pH of about 3.0 to about 10.0. In another embodiment, the composition contains an amount of particles in suspension equal to or greater than 10 m which is lower than 6000 particles per 100 ml, and preferably lower than 2000 particles per 100 ml. Uses of these compositions as a medicament is contemplated. Various therapeutic uses of these pharmaceutical compositions is also contemplated.

The present invention relates to a method for promoting the formation of mature NGF and increasing the expression of NGF. The method comprises administering a therapeutically effective amount of a plasminogen pathway activator to a subject. The present invention further relates to a pharmaceutical composition, a product and a kit comprising the plasminogen pathway activator for promoting the formation of mature NGF and increasing the expression of NGF.

The present invention relates to a method for promoting the formation of mature BDNF and increasing the level of BDNF. The method comprises administering a therapeutically effective amount of a plasminogen pathway activator to a subject. The present invention also relates to a pharmaceutical composition, a product and a kit which comprises the plasminogen pathway activator and are used for promoting the formation of mature BDNF and increasing the BDNF level.

Disclosed is a compound having the Formula (I): X-[NHCHR.sup.1C(O)NHCHR.sup.2C(O)].sub.xY (I) or a pharmaceutically acceptable salt or tautomer thereof, wherein R.sup.1 is H or the side chain of a neutral amino acid; R.sup.2 is the side chain of a basic amino acid R.sup.3; x is inclusive; X is H or a residue of a therapeutic agent; Y is OH, or a residue of a therapeutic agent; R.sup.3 is: [Formula should be inserted here]; R.sup.5 is a residue of a therapeutic agent; and provided that when R.sup.2 is R.sup.3, X is H and Y is OH. Also disclosed is a method of treating an ocular disorder, comprising: (a) intravitreal administration to an eye of a subject in need thereof with an effective amount of a therapeutic nanoparticle composition, the therapeutic nanoparticle composition comprising (i) at least one population of nanostructures and (ii) at least one peptide attached to the at least one population of nanostructures. The nanostructures may be exposed to light in the eye thereby electrostimulating the eye and treating the ocular disorder. Also disclosed is a method of treating an ocular disorder, comprising contacting the eye of a subject in need thereof with an effective amount of a therapeutic nanoparticle composition, the therapeutic nanoparticle composition comprising (i) at least one population of nanostructures, (ii) a peptide attached to the at least at least one population of nanostructures, (iii) a therapeutic agent useful for the treatment of the ocular disorder attached to the at least one population of nanostructures or to the peptide; and (iv) optionally, a linkage between the at least one population of nanostructures or the peptide and the therapeutic agent.

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The present invention relates to the use of plasminogen in the dissolution of fresh and old thrombus. Compared with other existing thrombolytic drugs, the plasminogen of the present invention can specifically dissolve thrombus without causing side effects such as bleeding. The drug of the present invention also has the advantages of dissolving both fresh and old thrombus, with a long half-life and controllable thrombolytic strength. Therefore, plasminogen may become a brand-new strategy for dissolving thrombus in vivo.

A system for the physical manipulation of free magnetic rotors in a circulatory system using a remotely placed magnetic field-generating stator is provided. In one embodiment, the invention relates to the control of magnetic particles 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. Examples of vascular occlusions targeted by the system include, but are not limited to, atherosclerotic plaques, including fibrous caps, fatty buildup, coronary occlusions, arterial stenosis, restenosis, vein thrombi, arterial thrombi, cerebral thrombi, embolisms, hemorrhages, other blood clots, and very small vessels.

The invention provides methods for enhancing the delivery of therapeutic compounds to the eye of a subject by administering plasmin or derivatives thereof and the therapeutic compounds to the eye.

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.