Methods of treating cardiac hypertrophy or cardiomyocyte hypertrophy, or methods of inhibiting progression of heart failure in a subject in need thereof, in which the methods comprise administering a pharmaceutical composition comprising an effective amount of a conjugate comprising microRNA and a cardiac targeting peptide. In addition, methods of inhibiting expression of Ca2+/calmodulin-dependent protein kinase II delta or histone deacetylase 4 in cardiomyocytes, in which the methods comprise contacting the cardiomyocytes with a conjugate comprising microRNA and a cardiac targeting peptide. The microRNA may be mi RN A 106a. miRNA17, miRNA20a, or miRNA93.

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

Methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency are disclosed in this patent application. The method of inducing rejuvenation in a population of adult glial progenitor cells, may comprise: administering, to the population of adult glial progenitor cells, one or more nucleic acid molecules encoding microRNAs, wherein administering suppresses the signal transducer and activator of transcription 3 (STAT3) signaling pathway; and/or administering microRNAs, wherein administering suppresses the E2F transcription factor 6 (E2F6) signaling pathway; and/or administering microRNAs, wherein administering suppresses the Myc-associated factor X (MAX) signaling pathway, wherein the one or more nucleic acid molecules are administered in an amount sufficient to induce rejuvenation in the population of adult glial progenitor cells.

The present invention provides workflows for the discovery of nonallosteric sirtuin activation compounds. Workflows enable drug discovery of novel sirtuin activating compounds with prescribed effects on the binding in pockets near the active site interacting with flexible protein degrees of freedom around the active site. Novel kinetic models are used to confirm hit compounds and to improve their properties.

The present invention relates to novel crystalline forms of a compound of formula I, or an adduct thereof:

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It further relates to methods of preparing such novel crystalline forms, to pharmaceutical compositions comprising them, methods of preparing the pharmaceutical compositions, and uses and medical treatments using the novel crystalline forms.