The present invention relates to methods and pharmaceutical compositions for the treatment of post-operative cognitive dysfunction. In particular, the present invention relates to a method of treating post-operative cognitive dysfunction in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an APJ receptor agonist.

The present invention relates to compositions comprising polyinosinic (poly(I))-polycytidylic acid poly(C) molecules, or a salt and/or solvate thereof, comprising double-stranded polyribonucleotides. The present invention further relates to compositions wherein the disclosed respective poly(I) and poly(C) single-stranded molecules are annealed to thereby form double-stranded poly(I:C) molecules.

The present invention relates to compositions comprising polyinosinic (poly(I))-polycytidylic acid poly(C) molecules, or a salt and/or solvate thereof, comprising double-stranded polyribonucleotides. The present invention further relates to compositions wherein the disclosed respective poly(I) and poly(C) single-stranded molecules are annealed to thereby form double-stranded poly(I:C) molecules.

This invention relates to novel method of treating or ameliorating a retinal disease or disorder or retinal degradation in a subject and a novel method of restoring retinal pigment epithelium cell compromising the administration of a one or more compounds which modulate Nox4, formation of radical oxygen species, serine protease, a dopamine receptor, NF-kB, mTOR, AMPK, RPE epithelial to mesenchymal transition, RPE dedifferentiation, or one or more Rho GTPases; and kits for administration of the methods.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):

##STR00001##

and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):

##STR00001##

and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

A composition inhibiting MEIS proteins. The MEIS proteins are effective in proliferation of hematopoietic stem cells. A formulation capable of easily passing through the cell membrane and perform its activity in the cell, and can inhibit MEIS activity in a dose dependent manner. The combination includes isolated cells, medium, growth factors and MEISi inhibitor. The isolated cells are isolated from mouse bone marrow, human bone marrow and human umbilical cord blood. The medium has a pH value of 7.2 and contains bovine serum albumin, recombinant insulin, transferrin, 2-mercaptoethanol and IMDM medium. The growth factors are hematopoietic stem cell factor SCF, fetus liver tyrosine kinase-3 ligand Flt3L, and thrombopoietin. A chemical formula of the MEISi-1 is 4-[2-(benzylamino)-2-oxoethoxy]-N-(2,3-dimethylphenyl) benzamide. A chemical formula of MEISi-2 is 4-hydroxy-N′-[(Z)-(2-oxonaphthalen-1-ylidene)methyl] benzohydrazide.

A composition inhibiting MEIS proteins. The MEIS proteins are effective in proliferation of hematopoietic stem cells. A formulation capable of easily passing through the cell membrane and perform its activity in the cell, and can inhibit MEIS activity in a dose dependent manner. The combination includes isolated cells, medium, growth factors and MEISi inhibitor. The isolated cells are isolated from mouse bone marrow, human bone marrow and human umbilical cord blood. The medium has a pH value of 7.2 and contains bovine serum albumin, recombinant insulin, transferrin, 2-mercaptoethanol and IMDM medium. The growth factors are hematopoietic stem cell factor SCF, fetus liver tyrosine kinase-3 ligand Flt3L, and thrombopoietin. A chemical formula of the MEISi-1 is 4-[2-(benzylamino)-2-oxoethoxy]-N-(2,3-dimethylphenyl) benzamide. A chemical formula of MEISi-2 is 4-hydroxy-N′-[(Z)-(2-oxonaphthalen-1-ylidene)methyl] benzohydrazide.

The present invention is drawn to the use of the compounds highlighted in Tables 1 & 2 and analogs thereof, for enhancing IR-mediated cellular cannibalism in cancer cells. Said compounds are herein called “enhancers of IR-mediated cellular cannibalism”. They can be used to enhance tumor immunogenicity and/or to induce a significant protective anticancer immune response in subjects that will receive or that have received a radiotherapy treatment. In other words, said compounds can be used to potentiate a radiotherapy treatment in a subject in need thereof. Said compounds are preferably chosen in the group consisting of: Mebhydroline 1,5-napthalene disulfonate salt, Flurbiprofen, Minaprine dihydrochloride, Myricetin, Digoxin, Digitoxin, Lanatoside, LOPA87, VP331, RN-1-026, SG6163F, VP450, and VP43.

The present invention is drawn to the use of the compounds highlighted in Tables 1 & 2 and analogs thereof, for enhancing IR-mediated cellular cannibalism in cancer cells. Said compounds are herein called “enhancers of IR-mediated cellular cannibalism”. They can be used to enhance tumor immunogenicity and/or to induce a significant protective anticancer immune response in subjects that will receive or that have received a radiotherapy treatment. In other words, said compounds can be used to potentiate a radiotherapy treatment in a subject in need thereof. Said compounds are preferably chosen in the group consisting of: Mebhydroline 1,5-napthalene disulfonate salt, Flurbiprofen, Minaprine dihydrochloride, Myricetin, Digoxin, Digitoxin, Lanatoside, LOPA87, VP331, RN-1-026, SG6163F, VP450, and VP43.