Modified peptides based on C-terminal PDZ binding domains of PTEN and PHLPP, or PDK1 interacting fragment of PKN2 are described as are methods of using the modified peptides for blocking the activity of PTEN, PHLPP and PKN2 and treating sudden cardiac arrest. A method for guiding treatment of cardiac arrest based on sorbitol or taurine levels is also provided.

A fusion protein and a complex containing same, capable of being used for the intracellular delivery of cargo molecules. The fusion protein and complex can implement the efficient release of cargo molecules from endocytic vesicles, thereby significantly improving the cytoplasmic delivery efficiency of the cargo molecules. One cargo molecules can be obtained in cytoplasms, they can exert any function related thereto. The fusion protein and complex provide effective means for affecting biological mechanisms and pathways of cells, and can be used in various fields such as research, treatment, and diagnosis.

The present invention concerns a method for expressing a recombinant DNA molecule in a eukaryotic host cell, comprising the steps of: (a) expressing or introducing at least one chimeric protein, in said host cell, wherein said chimeric protein comprises: (i) at least one catalytic domain of a capping enzyme, in particular selected in the group consisting of cap-0 canonical capping enzymes, cap-0 non-canonical capping enzymes, cap-1 capping enzymes and cap-2 capping enzymes; and (ii) at least one catalytic domain of a DNA-dependent RNA polymerase, in particular a bacteriophage DNA-dependent RNA polymerase, (b) constitutively or transiently downregulating the phosphorylation level of subunit a of translation initiation factor eIF2 (eIF2α) in said host cell.

The invention also concerns an isolated nucleic acid molecule or a set of nucleic acid molecules, comprising or consisting of (1) at least one nucleic acid sequence encoding a chimeric protein comprising at least one catalytic domain of a capping enzyme; and at least one catalytic domain of a DNA-dependent RNA polymerase; and (2) at least one nucleic acid sequence downregulating the phosphorylation level of eIF2α in a eukaryotic host cell or encoding a polypeptide downregulating said phosphorylation level; and (3) optionally, at least one nucleic acid sequence encoding a poly(A) polymerase, as well as vectors, kits and cells comprising said nucleic acid molecule or set, and different uses and applications thereof.

Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in de15q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Acα, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) myelodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

The present disclosure provides a recombinant, probiotic lactic acid bacterium, wherein the bacterium comprises a non-replicating plasmid vector comprising (a) a tumor suppressor gene or anti-inflammatory gene operably linked to a first promoter that directs expression of the tumor suppressor gene or anti-inflammatory gene in a mammalian cell, and (b) an adhesin gene operably linked to a second promoter that directs expression of the adhesin gene in the bacterium. The present disclosure also provides uses of the recombinant bacterium, and methods of constructing the recombinant bacterium. The present disclosure also provides a method of treating cancer in a subject, wherein the method comprises administering a pharmaceutically effective amount of a recombinant, probiotic lactic acid bacterium, wherein the bacterium comprises a non-replicating plasmid vector comprising an adhesin gene operably linked to a promoter that directs expression of the adhesin gene in the bacterium.

Provided herein are antibodies, or antigen-binding portions thereof, which specifically bind to pathologic forms of calcineurin. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and methods for use of these antibodies.

The present invention provides a method of treating heart failure with reduced ejection fraction, by administering to a patient at risk of such damage, a pharmaceutically effective amount of a composition which inhibits the anchoring of PP2A to mAKAPβ. This composition is preferably in the form of a viral based gene therapy vector that encodes a fragment of mAKAPβ to which PP2A binds.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

Described are novel immunosuppressant drug resistant armored (IDRA) T cells that co-express an exogenous T cell receptor (TCR) and one or more exogenous inhibitors of an immunosuppressant. The TCR can bind to an antigen expressed by a tumor cell or virally infected cell. Also described are methods of producing the modified T cell, and methods of treating a subject using the modified T cells.

Provided herein are antibodies, or antigen-binding portions thereof, which specifically bind to pathologic forms of calcineurin. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and methods for use of these antibodies.