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The most severe form of muscular dystrophy (MD), known as Duchenne MD (DMD), remains an incurable disease, hence the ongoing efforts to develop supportive therapies. The dysregulation of autophagy, a degradative yet protective mechanism activated when tissues are under severe and prolonged stress, is critically involved in DMD. Treatments that harness autophagic capacities therefore represent a promising therapeutic approach. Osmolytes are protective organic molecules that regulate osmotic pressure and cellular homeostasis and may support tissue-repairing autophagy. We therefore explored the effects of the osmolyte ectoine in the standard mouse model of DMD, the mdx, focusing on the autophagy-related proteome. Mice were treated with ectoine in their drinking water (150 mg/kg) or through daily intraperitoneal injection (177 mg/kg) until they were 5.5 weeks old. Hind limb muscles were dissected, and samples were prepared for Western blotting for protein quantification and for immunofluorescence for an evaluation of tissue distribution. We report changes in the protein levels of autophagy-related 5 (ATG5), Ser366-phosphorylated sequestosome 1 (SQSTM1), heat shock protein 70 (HSP70), activated microtubule-associated protein 1A/1B-light chain 3 (LC3 II) and mammalian target of rapamycin (mTOR). Most importantly, ectoine significantly improved the balance between LC3 II and SQSTM1 levels in mdx gastrocnemius muscle, and LC3 II immunostaining was most pronounced in muscle fibers of the tibialis anterior from treated mdx. These findings lend support for the further investigation of ectoine as a potential therapeutic intervention for DMD. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer treatment with the chemotherapy drug paclitaxel (PTX) is highly effective. Still, it can cause serious side effects, such as nerve damage (peripheral neuropathy) and a reduced ability to fight infections (neutropenia). These side effects lead to dose reductions or delays in treatment, which can impact patients' quality of life and the effectiveness of their care. Current dosing methods are based on body surface area but do not consider individual differences in muscle and fat levels or physical activity, which can influence how the drug is processed and tolerated. This study will explore how these factors interact with paclitaxel and contribute to side effects. We aim to develop a model that predicts these effects in women with breast cancer. This may help refine chemotherapy dosing and reduce side effects in the future. Background/Objectives: Paclitaxel (PTX), a commonly used chemotherapy for breast cancer (BC), is associated with dose-limiting toxicities (DLTs) such as peripheral neuropathy and neutropenia. These toxicities frequently lead to dose reductions, treatment delays, or therapy discontinuation, negatively affecting patients' quality of life and clinical outcomes. Current dosing strategies based on body surface area (BSA) fail to account for individual variations in body composition (skeletal muscle mass (SMM) and adipose tissue (AT) mass) and physical activity (PA), which can influence drug metabolism and toxicity. This study aims to explore the relationships between PTX pharmacokinetics, body composition, and PA to predict DLTs. Methods: This single-group observational cohort study will recruit 40 female BC patients undergoing PTX treatment. Data collection will include plasma PTX concentrations, body composition assessments (using dual X-ray absorptiometry and bioelectrical impedance analysis), PA measurements (via accelerometers), and questionnaires to assess BC-related health-related quality of life, chemotherapy-induced peripheral neuropathy, and neutropenia during the PTX schedule using validated questionnaires. Dose-limiting toxicities will be graded according to the Common Terminology Criteria for Adverse Events v5.0 (grade 3 or higher). This protocol is designed to develop a population-based PK-PD model that predicts the occurrence of chemotherapy-induced peripheral neuropathy and neutropenia in women with stage II or III BC undergoing PTX therapy, focusing on explanatory outcomes related to SMM, AT mass, and PA. [ABSTRACT FROM AUTHOR]