Poststroke hyperglycemia dysregulates cap-dependent translation in neural cells.

Aims: Post stroke hyperglycemia has been shown to deter functional recovery. Earlier findings have indicated the cap-dependent translation regulator 4E-BP1 is detrimentally upregulated in hyperglycemic conditions. The present study aims to test the hypothesis that hyperglycemic ischemic reperfusion injury (I/R) affects normal protein translation poststroke.

Loss of the mitochondrial protein mitoNEET in mice is associated with cognitive impairments and increased neuroinflammation.

Background: Mitochondrial dysfunction is implicated in several neurodegenerative diseases associated with memory and cognitive deficits, including Alzheimer's disease. Changes in bioenergetic function results in reactive oxygen species, oxidative damage and consequently neuroinflammation, which contributes to neuronal cell loss.

Objective: In this study, we evaluated the impact of the loss of the redox active [2Fe-2S] mitochondrial-associated protein mitoNEET (CISD1) on neuroinflammation and cognition using an age-appropriate preclinical model.

Synthesis and evaluation of enzyme inhibition by novel TT01001 derivatives as monoamine oxidase B inhibitors.

Monoamine oxidase (MAO) B is a promising target for treating stroke reperfusion injury, Parkinson's disease as well as other neurodegenerative diseases. Pharmacological inhibitors of this enzyme have demonstrated the ability to modulate critical neurotransmitter levels, decrease damaging reactive oxygen species and neuroinflammation, and improve mitochondrial dysfunction. We identified TT01001 from a pilot screen which showed good potency for inhibiting MAO-B, with a half-maximal inhibitory concentration below 10 μM.

Preclinical Multi-Omic Assessment of Pioglitazone in Skeletal Muscles of Mice Implanted with Human HER2/neu Overexpressing Breast Cancer Xenografts.

: Breast cancer (BC) is the second most commonly diagnosed cancer worldwide and is accompanied by fatigue during both active disease and remission in the majority of cases. Our lab has measured fatigue in isolated muscles from treatment-naive BC patient-derived orthotopic xenograft (BC-PDOX) mice. Here, we conducted a preclinical trial of pioglitazone in BC-PDOX mice to determine its efficacy in ameliorating BC-induced muscle fatigue, as well as its effects on transcriptomic, metabolomic, and lipidomic profiles in skeletal muscle.

Preclinical evaluation of ELP-004 in mice.

This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP-004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease-modifying antirheumatic drugs, are not well-tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP-004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed.