Provided herein are retinoid X receptor alpha binders that specifically bind to an epitope of a retinoid X receptor alpha, wherein the epitope comprises a phosphorylated serine at position 56 or 70. Also provided herein are retinoid X receptor alpha/polo-like kinase 1 modulators that inhibit the interaction of a polo-like kinase 1 with a retinoid X receptor alpha comprising a phosphorylated serine at position 56 or 70.

The present disclosure provides compositions and methods for the treatment of PPARG activated cancer. For example, the present disclosure provides PPARG signaling modulators for the treatment of bladder cancer. In particular, therapeutic and/or prophylactic compositions and uses of PPARG inverse-agonists are described.

Provided herein are, inter alia, antibodies (e.g. humanized antibodies, monoclonal antibodies, antibody fragments (e.g., scFvs) and antibody compositions (e.g., chimeric antigen receptors, bispecific antibodies), which bind human tyrosine kinase-like orphan receptor 1 (ROR1) with high efficiency and specificity. The antibodies and antibody compositions provided herein include novel light and heavy chain domain CDRs and framework regions and are, inter alia, useful for diagnosing and treating cancer and other ROR1-related diseases.

A novel omega-3 fatty acid/lipid based nutraceutical composition and a method of optimizing said omega-3 fatty acid/lipid based nutraceutical composition. The nutraceutical composition and method is based on the insight that different forms of high omega-3 fatty acid lipids (e.g. triglyceride form, ethyl ester form, free fatty acid form, phospholipid form) have different molecular modes and levels of action. Specifically the phospholipid form is likely more effective at promoting membrane fluidity and permeability, while the free fatty acid form is likely more effective at regulating cell receptors, such as the PPARa receptors, that are responsible for various metabolic effects including lipid metabolism. The desirability of producing omega-3 compositions that may act synergistically and thus more robustly to improve health and to some extent mimic markers of life extension such as shown by caloric restriction, along with specific optimization methods, markers, and compositions are taught.

Methods of screening a compound for susceptibility to causing systemic or hepatic toxicity, using a hepatic cell system exposed to a range of concentrations of a bile acid in the absence or presence of a compound to determine a toxicity profile. In vitro systems for predicting in vivo hepatotoxic potential of a compound are also provided, and include in vitro cultured hepatic cell systems with a capacity for bile acid synthesis, bile acid transport and bile acid regulation.

Methods of preventing or treating Parkinson's disease in subjects are described where drugs are administered to subjects in effective amounts to cause the farnesylation of PARIS and the enhanced expression of PGC-1 in the brain. These methods alleviate the effects of Parkinson's disease in subjects, in part, by preventing the loss of dopamine neurons.

The current disclosure provides specific peptides, and derived ionization characteristics of the peptides from the estrogen receptor (ER), progesterone receptor (PR), and/or antigen Ki67 (Ki67) proteins that are particularly advantageous for quantifying the ER, PR, and/or Ki67 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue reagents and protocol, and the ER, PR, and/or Ki67 proteins are quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the ER, PR, and/or Ki67 proteins. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of an ER, PR, and/or Ki67 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

The invention relates to cardiovascular disease, and particularly, although not exclusively, to cardiovascular disease biomarkers and their use in methods of diagnosis and prognosis. The invention also extends to diagnostic and prognostic kits utilising the biomarkers of the invention for diagnosing or prognosing cardiovascular disease.

Ex vivo and in vivo methods of expansion of renewable stem cells, expanded populations of renewable stem cells and their uses.

Provided is a method for suppressing an adipose differentiation comprising administering to a subject in need thereof a PPAR-v neddylation inhibitor for inhibiting adipocyte differentiation and a method for screening an adipocyte differentiation inhibitor using PPAR-v neddylation associated with adipocyte differentiation. The inhibitor of a neddylation pathway of PPAR-v inhibits the differentiation from mesenchymal stem cells to mast cells, and thus can be effectively used to treat obesity, and particularly, can be also useful in the treatment of severe obesity which cannot be excepted to be treated by existing obesity treatment agents.