Mitochondrial-targeted plastoquinone therapy ameliorates early onset muscle weakness that precedes ovarian cancer cachexia in mice.

Cancer cachexia, and the related loss of muscle and strength, worsens quality of life and lowers overall survival. Recently, a novel 'pre-atrophy' muscle weakness was identified during early-stage cancer. While mitochondrial stress responses are associated with early-stage pre-atrophy weakness, a causal relationship has not been established.

Mitohormesis during advanced stages of Duchenne muscular dystrophy reveals a redox-sensitive creatine pathway that can be enhanced by the mitochondrial-targeting peptide SBT-20.

Mitochondrial creatine kinase (mtCK) regulates the "fast" export of phosphocreatine to support cytoplasmic phosphorylation of ADP to ATP which is more rapid than direct ATP export. Such "creatine-dependent" phosphate shuttling is attenuated in several muscles, including the heart, of the D2.mdx mouse model of Duchenne muscular dystrophy at only 4 weeks of age.

Recent Advances in Pre-Clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles.

Cardiomyopathy in Duchenne Muscular Dystrophy and the Potential for Mitochondrial Therapeutics to Improve Treatment Response.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene, resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with the development of cardiomyopathy-the leading cause of death-inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge.

Cardiac Atrophy, Dysfunction, and Metabolic Impairments: A Cancer-Induced Cardiomyopathy Phenotype.

Muscle atrophy and weakness are prevalent features of cancer. Although extensive research has characterized skeletal muscle wasting in cancer cachexia, limited studies have investigated how cardiac structure and function are affected by therapy-naive cancer. Herein, orthotopic, syngeneic models of epithelial ovarian cancer and pancreatic ductal adenocarcinoma, and a patient-derived pancreatic xenograft model, were used to define the impact of malignancy on cardiac structure, function, and metabolism.

Muscle mitochondrial function is impaired in adults with type 1 diabetes.

Aims: Type 1 diabetes has been associated with mitochondrial dysfunction. However, the mechanism of this dysfunction in adults remains unclear.

Methods: A secondary analysis was conducted using data from several clinical trials measuring in-vivo and ex-vivo mitochondrial function in adults with type 1 diabetes (n = 34, age 38.

Initial validation of the Turkish version of the defense mechanisms rating scales-self-report-30.

The Defense Mechanisms Rating Scales-Self Report-30 (DMRS-SR-30) was recently developed to add a self-report alternative to the assessment of defenses, reflecting their generally accepted hierarchical organization. In this study, we aimed to examine psychometric properties and factor structure of the Turkish language version of the DMRS-SR-30. The sample consisted of 1.

Skeletal muscle mitochondrial morphology negatively affected in mice lacking Xin.

Altered mitochondrial structure and function are implicated in the functional decline of skeletal muscle. Numerous cytoskeletal proteins are known to affect mitochondrial homeostasis, but this complex network is still being unraveled. Here, we investigated mitochondrial alterations in mice lacking the cytoskeletal adapter protein, XIN (XIN-/-).

Targeting skeletal muscle health with exercise in people with type 1 diabetes: A protocol for HOMET1D, a prospective observational trial with matched controls.

Introduction: Individuals with type 1 diabetes (T1D) experience a complex set of alterations to skeletal muscle metabolic, neuromuscular, and vascular health; collectively referred to as diabetic myopathy. While the full scope of diabetic myopathy is still being elucidated, evidence suggests that even when individuals with T1D are physically active, indices of myopathy still exist. As such, there is a question if adherence to current physical activity guidelines elicits improvements in skeletal muscle health indices similarly between individuals with and without T1D.

The mental health of migrants living in limbo: A mixed-methods systematic review with meta-analysis.

The number of forcibly displaced people has more than doubled over the past decade. Many people fleeing are left in limbo without a secure pathway to citizenship or residency. This mixed-methods systematic review reports the prevalence of mental disorders in migrants living in limbo, the association between limbo and mental illness, and the experiences of these migrants in high income countries.

Muscle weakness and mitochondrial stress occur before metastasis in a novel mouse model of ovarian cancer cachexia.

Objectives: A high proportion of women with advanced epithelial ovarian cancer (EOC) experience weakness and cachexia. This relationship is associated with increased morbidity and mortality. EOC is the most lethal gynecological cancer, yet no preclinical cachexia model has demonstrated the combined hallmark features of metastasis, ascites development, muscle loss and weakness in adult immunocompetent mice.

Designing Gold Nanoparticles for Precise Glioma Treatment: Challenges and Alternatives.

Glioblastoma multiforme (GBM) is a glioma and the most aggressive type of brain tumor with a dismal average survival time, despite the standard of care. One promising alternative therapy is boron neutron capture therapy (BNCT), which is a noninvasive therapy for treating locally invasive malignant tumors, such as glioma. BNCT involves boron-10 isotope capturing neutrons to form boron-11, which then releases radiation directly into tumor cells with minimal damage to healthy tissues.

Defense mechanisms are associated with mental health symptoms across six countries.

Defense mechanisms are adaptative processes that are related to mental health and psychological functioning and may play an important role in adaptation to distress, as well as in mental health interventions. The present study aimed to compare the use of defense mechanisms and their relationship to mental health symptoms across six countries. In a large-scale descriptive study, we collected data from community- based individuals (N=19,860) in the United States, Australia, Canada, Germany, Italy, and the United Kingdom about the use of defense mechanisms and experienced mental health symptoms during the early phase of the pandemic.

The slow-release adiponectin analog ALY688-SR modifies early-stage disease development in the D2. mouse model of Duchenne muscular dystrophy.

Fibrosis is associated with respiratory and limb muscle atrophy in Duchenne muscular dystrophy (DMD). Current standard of care partially delays the progression of this myopathy but there remains an unmet need to develop additional therapies. Adiponectin receptor agonism has emerged as a possible therapeutic target to lower inflammation and improve metabolism in mouse models of DMD but the degree to which fibrosis and atrophy are prevented remain unknown.

Deep spatial-omics analysis of Head & Neck carcinomas provides alternative therapeutic targets and rationale for treatment failure.

Immune checkpoint inhibitor (ICI) therapy has had limited success (<30%) in treating metastatic recurrent Head and Neck Oropharyngeal Squamous Cell Carcinomas (OPSCCs). We postulate that spatial determinants in the tumor play a critical role in cancer therapy outcomes. Here, we describe the case of a male patient diagnosed with p16 OPSCC and extensive lung metastatic disease who failed Nivolumab and Pembrolizumab/Lenvatinib therapies.

Skin-Grafting and Dendritic Cell "Boosted" Humanized Mouse Models Allow the Pre-Clinical Evaluation of Therapeutic Cancer Vaccines.

Vaccines have been hailed as one of the most remarkable medical advancements in human history, and their potential for treating cancer by generating or expanding anti-tumor T cells has garnered significant interest in recent years. However, the limited efficacy of therapeutic cancer vaccines in clinical trials can be partially attributed to the inadequacy of current preclinical mouse models in recapitulating the complexities of the human immune system. In this study, we developed two innovative humanized mouse models to assess the immunogenicity and therapeutic effectiveness of vaccines targeting human papillomavirus (HPV16) antigens and delivering tumor antigens to human CD141 dendritic cells (DCs).

Insights into product and process related challenges of lentiviral vector bioprocessing.

Lentiviral vectors (LVs) are used in advanced therapies to transduce recipient cells for long term gene expression for therapeutic benefit. The vector is commonly pseudotyped with alternative viral envelope proteins to improve tropism and is selected for enhanced functional titers. However, their impact on manufacturing and the success of individual bioprocessing unit operations is seldom demonstrated.

Memory impairment in the D2.mdx mouse model of Duchenne muscular dystrophy is prevented by the adiponectin receptor agonist ALY688.

New Findings: What is the central question of this study? Can adiponectin receptor agonism improve recognition memory in a mouse model of Duchenne muscular dystrophy? What is the main finding and its importance? Short-term treatment with the new adiponectin receptor agonist ALY688 improves recognition memory in D2.mdx mice. This finding suggests that further investigation into adiponectin receptor agonism is warranted, given that there remains an unmet need for clinical approaches to treat this cognitive dysfunction in people with Duchenne muscular dystrophy.

Mitochondrial creatine sensitivity is lost in the D2. model of Duchenne muscular dystrophy and rescued by the mitochondrial-enhancing compound Olesoxime.

Duchenne muscular dystrophy (DMD) is associated with distinct mitochondrial stress responses. Here, we aimed to determine whether the prospective mitochondrial-enhancing compound Olesoxime, prevents early-stage mitochondrial stress in limb and respiratory muscle from D2. mice using a proof-of-concept short-term regimen spanning 10-28 days of age.

Assessment of Cardiovascular Risk for Noncardiac and Nonsurgical Activities.

Cardiovascular risk stratification is a frequent evaluation performed by health professionals. Not uncommonly, requests for risk stratification involve activities or procedures that fall outside of the scope of current evidence-based guidelines. Estimating risk and providing guidance for these requests can be challenging due to limited available evidence.

Gold Nanostar Characterization by Nanoparticle Tracking Analysis.

We demonstrate the application of nanoparticle tracking analysis (NTA) for the quantitative characterization of gold nanostars (GNSs). GNSs were synthesized by the seed-mediated growth method using triblock copolymer (TBP) gold nanoparticles (GNPs). These GNPs (≈ 10 nm) were synthesized from Au (≈ 1 mM) in aqueous F127 (w/v 5%) containing the co-reductant ascorbic acid (≈ 2 mM).

Scientific meeting report: International Biochemistry of Exercise 2022.

Exercise is one of the only nonpharmacological remedies known to counteract genetic and chronic diseases by enhancing health and improving life span. Although the many benefits of regular physical activity have been recognized for some time, the intricate and complex signaling systems triggered at the onset of exercise have only recently begun to be uncovered. Exercising muscles initiate a coordinated, multisystemic, metabolic rewiring, which is communicated to distant organs by various molecular mediators.