The present disclosure provides a therapy for diabetes that targets abnormal stem cells in combination with stem cell migration. In one embodiment, the present disclosure provides a therapy for diabetes and/or diabetes-related diseases and disorders and/or symptoms that targets abnormal stem cells in combination with stem cell migration. In one embodiment, the present disclosure provides diagnosis of diabetes and/or diabetes-related diseases and disorders and/or symptoms, or the risk thereof, using abnormal stem cell migration and/or residence as an indicator.

The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

Disclosed herein are nanoparticles comprising a lipid core comprising a sterol; and a complex comprising a cationic agent and a therapeutic agent, wherein the complex is encapsulated within the lipid core. Methods to produce the nanoparticle comprise: combining a cationic agent, a therapeutic agent, and a first water-immiscible solvent with a first aqueous solution, thereby forming a mixture comprising a complex comprising the cationic agent and the therapeutic agent; combining the mixture with a second waterim-miscible solvent, thereby forming an aqueous phase and an organic phase, and separating the organic phase comprising the complex; combining the organic phase comprising the complex with a sterol and a first water-miscible organic solvent; and dispersing the complex in a second aqueous solution to form a herein disclosed nanoparticle. Methods for treating a disease and for reducing nanoparticle burst rate are also disclosed.

Disclosed herein are nanoparticles comprising a lipid core comprising a sterol; and a complex comprising a cationic agent and a therapeutic agent, wherein the complex is encapsulated within the lipid core. Methods to produce the nanoparticle comprise: combining a cationic agent, a therapeutic agent, and a first water-immiscible solvent with a first aqueous solution, thereby forming a mixture comprising a complex comprising the cationic agent and the therapeutic agent; combining the mixture with a second waterim-miscible solvent, thereby forming an aqueous phase and an organic phase, and separating the organic phase comprising the complex; combining the organic phase comprising the complex with a sterol and a first water-miscible organic solvent; and dispersing the complex in a second aqueous solution to form a herein disclosed nanoparticle. Methods for treating a disease and for reducing nanoparticle burst rate are also disclosed.

Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R.sup.1a, R.sup.1b, L.sup.1, L.sup.2, L.sup.3, X, A, B and C are as defined as set forth in the specification. Also provided compounds of Formula IA for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.

##STR00001##

The present disclosure provides pharmaceutical combinations comprising at least one spliceosome modulator and at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors. Also provided are methods of treating cancer comprising administering a therapeutically effective amount of at least one spliceosome modulator and a therapeutically effective amount of at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors.

The present disclosure provides pharmaceutical combinations comprising at least one spliceosome modulator and at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors. Also provided are methods of treating cancer comprising administering a therapeutically effective amount of at least one spliceosome modulator and a therapeutically effective amount of at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors.

The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in methods of treating disease and for imaging of disease.