Provided here are arylpiperazine pharmacophore compositions that mitigate levodopa-induced dyskinesia and significantly improve Parkinson's disease-like symptoms. These dopamine D3 receptor ligands have high affinity and selectivity, are orally active, and have desirable drug-like properties.

Heart failure with preserved ejection fraction (HFpEF) which results from diastolic dysfunction is a growing epidemiologic problem. However, the pathophysiology of this disease is poorly understood. Our goal is to investigate whether microvessel disease may promote HFpEF. To do so we have used Leptin receptor deficient (Lepr.sup.db/db) female mice as a model of HFpEF and performed a transcriptomic analysis via RNA sequencing of the cardiac vascular fraction of both these mice and their control Lepr.sup.db/+littermates. In Lepr.sup.db/db female mice, end diastolic pressure (EDP) signing diastolic dysfunction is significantly increased from 3 month of age. It is correlated with a cardiac and cardiomayocyte hypertrophy, vascular leakage, endothelial cell activation and leucocyte infiltration. As expected, the RNA sequencing analysis confirmed endothelial dysfunction. Besides, it also revealed a strong increase in several mast cell markers. We confirmed, via histology, an accumulation of mast cells in the heart of Lepr.sup.db/db mice. Importantly, it was associated with increased levels of circulating IgE. Lepr.sup.db/db mice were then treated or not with Cromolyn sodium, an inhibitor of mast cell degranulation. After a month treatment, EDP was significantly reduced in Lepr.sup.db/db mice demonstrating the critical role of mast cell in the development of diastolic dysfunction in diabetic obese mice.

The present disclosure provides methods of treating a subject having decreased bone mineral density or at risk of developing decreased bone mineral density, and methods of identifying subjects having an increased risk of developing decreased bone mineral density.

The present disclosure provides methods of treating a subject having decreased bone mineral density or at risk of developing decreased bone mineral density, and methods of identifying subjects having an increased risk of developing decreased bone mineral density.

The present invention describes a pharmaceutical composition that includes a novel molecule with neuroprotective activity, to inhibit the neuroadaptations induced by opioids (tolerance and hyperalgesia) that lead to the successive escalation of its doses in the treatment of pain. In this way, it increases its analgesic efficacy in normal conditions and in neural damage, since this favors the appearance of tolerance/hyperalgesia and resistance to opioid treatment. Likewise, reduce the spontaneous signs of withdrawal associated with its withdrawal and consequently physical dependence and possible addiction. In addition, it describes a method for the treatment of pain with a neuropathic component that is supported by drug interaction and safety studies that show its synergy for the mechanical antihypernociceptive effect.

The present invention describes a pharmaceutical composition that includes a novel molecule with neuroprotective activity, to inhibit the neuroadaptations induced by opioids (tolerance and hyperalgesia) that lead to the successive escalation of its doses in the treatment of pain. In this way, it increases its analgesic efficacy in normal conditions and in neural damage, since this favors the appearance of tolerance/hyperalgesia and resistance to opioid treatment. Likewise, reduce the spontaneous signs of withdrawal associated with its withdrawal and consequently physical dependence and possible addiction. In addition, it describes a method for the treatment of pain with a neuropathic component that is supported by drug interaction and safety studies that show its synergy for the mechanical antihypernociceptive effect.

The invention relates to a method for in vitro predicting the outcome of an individual having a multiple myeloma, comprising the steps of: a. measuring the expression level of genes coding for kinases, b. calculating a score value for each genes; and c. classifying the individual as having a good or a bad outcome.

The invention relates to a method for in vitro predicting the outcome of an individual having a multiple myeloma, comprising the steps of: a. measuring the expression level of genes coding for kinases, b. calculating a score value for each genes; and c. classifying the individual as having a good or a bad outcome.

A therapeutic compound having intrinsic anti-mitochondrial properties may be chemically modified to target the compound to mitochondria, and the resulting “repurposcins” may have enhanced anti-cancer properties, among other advantageous properties. For example, a repurposcin may be used to treat and/or prevent tumor recurrence, metastasis, drug resistance, and/or radiotherapy resistance. Described herein are repurposcin compounds and pharmaceutical compositions that have been developed according to the present approach. Also described are methods for identifying and developing repurposcins, methods of using repurposcins to target cancer stem cells, and compositions for treating cancer containing one or more repurposcins as the active ingredient.

A therapeutic compound having intrinsic anti-mitochondrial properties may be chemically modified to target the compound to mitochondria, and the resulting “repurposcins” may have enhanced anti-cancer properties, among other advantageous properties. For example, a repurposcin may be used to treat and/or prevent tumor recurrence, metastasis, drug resistance, and/or radiotherapy resistance. Described herein are repurposcin compounds and pharmaceutical compositions that have been developed according to the present approach. Also described are methods for identifying and developing repurposcins, methods of using repurposcins to target cancer stem cells, and compositions for treating cancer containing one or more repurposcins as the active ingredient.