The critical role of mitochondrial dysfunction in ADT-induced neurotoxicity
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Survival outcomes of apalutamide as a starting treatment: impact in real-world patients with metastatic hormone sensitive prostate cancer (OASIS)
Androgen receptor pathway inhibitors (apalutamide [APA], enzalutamide [ENZ], abiraterone acetate plus prednisone [AAP]) combined with androgen-deprivation therapy (ADT) are effective life-prolonging treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the impact of upfront therapy for mHSPC on outcomes in real-world clinical practice in the United States.
Engineered mitochondria in diseases: mechanisms, strategies, and applications
Mitochondrial diseases represent one of the most prevalent and debilitating categories of hereditary disorders, characterized by significant genetic, biological, and clinical heterogeneity, which has driven the development of the field of engineered mitochondria. With the growing recognition of the pathogenic role of damaged mitochondria in aging, oxidative disorders, inflammatory diseases, and cancer, the application of engineered mitochondria has expanded to those non-hereditary contexts (sometimes referred to as mitochondria-related diseases). Due to their unique non-eukaryotic origins and endosymbiotic relationship, mitochondria are considered highly suitable for gene editing and intercellular transplantation, and remarkable progress has been achieved in two promising therapeutic strategies—mitochondrial gene editing and artificial mitochondrial transfer (collectively referred to as engineered mitochondria in this review) over the past two decades. Here, we provide a comprehensive review of the mechanisms and recent advancements in the development of engineered mitochondria for therapeutic applications, alongside a concise summary of potential clinical implications and supporting evidence from preclinical and clinical studies. Additionally, an emerging and potentially feasible approach involves ex vivo mitochondrial editing, followed by selection and transplantation, which holds the potential to overcome limitations such as reduced in vivo operability and the introduction of allogeneic mitochondrial heterogeneity, thereby broadening the applicability of engineered mitochondria.
Energy metabolism in health and diseases
Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, extensive metabolic reprogramming occurs, resulting in impaired glucose metabolism and mitochondrial dysfunction, which accelerate disease progression. Recent investigations into key regulatory pathways, including mechanistic target of rapamycin, sirtuins, and adenosine monophosphate-activated protein kinase, have considerably deepened our understanding of metabolic dysregulation and opened new avenues for therapeutic innovation. Emerging technologies, such as fluorescent probes, nano-biomaterials, and metabolomic analyses, promise substantial improvements in diagnostic precision. This review critically examines recent advancements and ongoing challenges in metabolism research, emphasizing its potential for precision diagnostics and personalized therapeutic interventions. Future studies should prioritize unraveling the regulatory mechanisms of energy metabolism and the dynamics of intercellular energy interactions. Integrating cutting-edge gene-editing technologies and multi-omics approaches, the development of multi-target pharmaceuticals in synergy with existing therapies such as immunotherapy and dietary interventions could enhance therapeutic efficacy. Personalized metabolic analysis is indispensable for crafting tailored treatment protocols, ultimately providing more accurate medical solutions for patients. This review aims to deepen the understanding and improve the application of energy metabolism to drive innovative diagnostic and therapeutic strategies.
Androgen deprivation therapy does not increase rates for reintervention, complication, or infection in primary penile implant or artificial urinary sphincter surgery: a retrospective cohort study from the TriNetX network
Prostate cancer treatment-related erectile dysfunction and stress urinary incontinence are commonly treated with inflatable penile prosthesis (IPP) or artificial urinary sphincter (AUS). Given the association with androgens and penile/urethral health, we aim to evaluate whether patients on androgen deprivation therapy (ADT) undergoing IPP or AUS surgery are at increased risk for reintervention, complication, or infection. We queried the TriNetX database for adult males receiving IPP or AUS. The ADT cohort included those on ADT 3 months before or any time after surgery. We performed sub-analysis for leuprolide and bicalutamide. Cohorts and outcomes were defined by Current Procedural Terminology and International Classification of Diseases codes. Propensity score matching was performed using age, prostate cancer, history of prostatectomy, and history of radiation. Outcomes were reintervention (revision, removal, or replacement), infection, and complication. Analytics were performed in March 2024. 13,432 patients received an IPP and 5676 received an AUS, 465 and 745 of whom were on ADT, respectively. The only significant AUS analysis was for patients on abiraterone having fewer reinterventions (10.5% vs 20.8%, RR = 0.50 [0.29, 0.88]). Patients receiving an IPP with ADT had fewer reinterventions (7.2% vs 12%, RR = 0.60 [0.39, 0.92]) and complications (12.7% vs 18.5%, RR = 0.68 [0.49, 0.95]). Those on a GnRH agonist had fewer reinterventions (7.4% vs 11.7%, RR = 0.63 [0.41, 0.98]) for IPP. Patients receiving an IPP on bicalutamide had fewer reinterventions ( <5.2%* vs 10.8%, RR = 0.48 [0.23, 0.99]) and on leuprolide had fewer complications (12.2% vs 19.3%, RR = 0.63 [0.43, 0.91]). The remainder of analyses showed no significant differences. Patients with IPP or AUS do not fare worse on ADT. Further evaluation into the duration of ADT may provide clinical context, but based on these results, ADT should not limit implant surgery.
Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects
The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.
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