The present invention provides, among other things, an improved method of treating cystic fibrosis (CF) in a human subject. The method comprises administration of a composition comprising an mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein by nebulization at a dose between 7 mg and 25 mg. A suitable dose for use in the method of the invention is selected on the basis that it provides the human subject with at least a 3% increase in absolute change in ppFEV1 (percent predicted forced expiratory volume in one second) from baseline ppFEV1 at two days following the administration. In addition or alternatively, the dose is selected to provide the human subject with at least a 2% increase in absolute change in ppFEV1 from baseline ppFEV1 at one week following the administration. In addition or alternatively, the dose is selected to provide the human subject with at least a 4% maximum increase in absolute change in ppFEV1 from baseline ppFEV1 through one week following administration.

Materials and methods for regulating lipid abundance by modulating Protease Activated Receptor 1 (PAR1) and Protease Activated Receptor 2 (PAR2) levels arc provided herein. In a first aspect, this document features a method that includes (a) identifying a mammal as having a condition characterized at least by impaired lipid production, impaired cholesterol production, or both impaired lipid production and impaired cholesterol production; and (b) administering to the mammal an inhibitor of PAR1 and/or PAR2 in an amount effective to increase lipid production and/or cholesterol production in the mammal.

Materials and methods for regulating lipid abundance by modulating Protease Activated Receptor 1 (PAR1) and Protease Activated Receptor 2 (PAR2) levels arc provided herein. In a first aspect, this document features a method that includes (a) identifying a mammal as having a condition characterized at least by impaired lipid production, impaired cholesterol production, or both impaired lipid production and impaired cholesterol production; and (b) administering to the mammal an inhibitor of PAR1 and/or PAR2 in an amount effective to increase lipid production and/or cholesterol production in the mammal.

The invention relates to compositions of nicotinamide mononucleotide derivatives and their methods of use. The invention also relates to methods of preparing nicotinamide mononucleotide derivatives. The invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinamide mononucleotide derivative. The invention relates to methods of using nicotinamide mononucleotide derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and improving cell and tissue survival.

The invention relates to compositions of nicotinamide mononucleotide derivatives and their methods of use. The invention also relates to methods of preparing nicotinamide mononucleotide derivatives. The invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinamide mononucleotide derivative. The invention relates to methods of using nicotinamide mononucleotide derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and improving cell and tissue survival.

A method of modulating growth factor responses of cells expressing C3a receptor (C3aR) and C5a receptor (C5aR) and at least one growth factor receptor includes administering to the cells a thrombin inhibitor.

The present invention provides compounds of formula I:

##STR00001##

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds, and methods of using such compounds for treatment of joint damage or joint injury in a mammal, and for inducing differentiation of mesenchymal stem cells into chondrocytes.

The present invention provides compounds of formula I:

##STR00001##

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds, and methods of using such compounds for treatment of joint damage or joint injury in a mammal, and for inducing differentiation of mesenchymal stem cells into chondrocytes.

Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.

Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.