Antibodies to the enzyme matriptase-2 (MTP-2) are presented. Inhibiting MTP-2 reduces uptake of dietary iron and reduces the release of iron from cellular stores in the body. Inhibitors of MTP-2 (such as antibodies to the serine protease domain) can be used to treat iron overload, which is a feature of diseases such as beta-thalassaemia and which otherwise leads to toxic accumulation of iron. Combination of an MTP-2 inhibitor with an activin receptor ligand trap, or with erythropoietin, provides additional therapeutic effects.

The present invention relates to a 6-6 bicyclic ring-containing compound derivative and use thereof. The compound according to the present invention acts as a PRMT5 inhibitor, and thus can be effectively used in the prevention or treatment of diseases caused by PRMT5.

A pharmaceutical composition comprising: a) an effective amount of an Inhibitors of Apoptosis Proteins (IAP) inhibitor, wherein the IAP inhibitor is represented by formula (I): or a pharmaceutically acceptable salt thereof, the definitions of each variable are provided herein; b) an effective amount of a second inhibitor, wherein the second inhibitor is a poly ADP ribose polymerase (PARP) inhibitor or a mitogen-activated protein kinase kinase (MEK) inhibitor; and a pharmaceutically acceptable carrier or diluent.

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Disclosed are compositions and methods for treating sickle cell disease. Also disclosed are methods of treating sickle cell disease comprising administering to a subject in need thereof an effective amount of isoquercetin, vitamin B3, vitamin C, and optionally folic acid and wherein the effective amount is sufficient to halt progression of one or more of the symptoms of sickle cell disease.

Disclosed are compositions and methods for treating sickle cell disease. Also disclosed are methods of treating sickle cell disease comprising administering to a subject in need thereof an effective amount of isoquercetin, vitamin B3, vitamin C, and optionally folic acid and wherein the effective amount is sufficient to halt progression of one or more of the symptoms of sickle cell disease.

The present disclosure relates to methods for increasing telomere length in one or more human cells and/or increasing genome stability of one or more human cells, for example by contacting one or more human cells with an agent that increases expression of Zscan4 in the one or more human cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a genomic and/or chromosome abnormality, of rejuvenating one or more human cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 are also provided.

The present disclosure provides methods and compositions for modulating expression of a target gene in a cell by reducing binding of an endogenous transcription factor to a regulatory sequence of the target gene. The method includes introducing into the cell a DNA binding polypeptide (DBF) that binds a sequence in regulatory region of a target gene bound by a transcription factor (TF), thereby displacing the TF and modulating expression of the target gene. The DBF may be designed to bind a sequence comprising the binding site for the TF and additional nucleotides present on one or both sides of the sequence. Accordingly, the DBF specifically binds to binding site for the TF in the target gene but not in other genes that are also regulated by binding of the TF but do not include the nucleotides present on one or both sides of the sequence.

The present disclosure provides methods and compositions for modulating expression of a target gene in a cell by reducing binding of an endogenous transcription factor to a regulatory sequence of the target gene. The method includes introducing into the cell a DNA binding polypeptide (DBF) that binds a sequence in regulatory region of a target gene bound by a transcription factor (TF), thereby displacing the TF and modulating expression of the target gene. The DBF may be designed to bind a sequence comprising the binding site for the TF and additional nucleotides present on one or both sides of the sequence. Accordingly, the DBF specifically binds to binding site for the TF in the target gene but not in other genes that are also regulated by binding of the TF but do not include the nucleotides present on one or both sides of the sequence.

The described invention identifies endothelial cells within the perivascular niche as a crucial component in driving bone marrow (BM) inflammation and HSC dysfunction. We demonstrate that crosstalk between ERK-MAPK and NF-κB signaling pathways within the endothelium plays a key role in modulating the outcomes of chronic inflammation. Sustained activation of the MAPK pathway selectively within the endothelium of adult mice leads to inflammation-induced HSC dysfunction including loss of engraftment ability and a myeloid-biased output. HSC defects caused by endothelial MAPK activation are completely resolved upon simultaneous inhibition of endothelial NF-κB signaling. The described invention identifies Stem Cell Growth Factor alpha (SCGF) as a niche-derived factor that suppresses BM inflammation and enhances hematopoietic recovery following myelosuppressive injury.

The described invention identifies endothelial cells within the perivascular niche as a crucial component in driving bone marrow (BM) inflammation and HSC dysfunction. We demonstrate that crosstalk between ERK-MAPK and NF-κB signaling pathways within the endothelium plays a key role in modulating the outcomes of chronic inflammation. Sustained activation of the MAPK pathway selectively within the endothelium of adult mice leads to inflammation-induced HSC dysfunction including loss of engraftment ability and a myeloid-biased output. HSC defects caused by endothelial MAPK activation are completely resolved upon simultaneous inhibition of endothelial NF-κB signaling. The described invention identifies Stem Cell Growth Factor alpha (SCGF) as a niche-derived factor that suppresses BM inflammation and enhances hematopoietic recovery following myelosuppressive injury.