Mitochondrial dysfunction and skeletal muscle atrophy: Causes, mechanisms, and treatment strategies.

Skeletal muscle, which accounts for approximately 40% of total body weight, is one of the most dynamic and plastic tissues in the human body and plays a vital role in movement, posture and force production. More than just a component of the locomotor system, skeletal muscle functions as an endocrine organ capable of producing and secreting hundreds of bioactive molecules. Therefore, maintaining healthy skeletal muscles is crucial for supporting overall body health. Various pathological conditions, such as prolonged immobilization, cachexia, aging, drug-induced toxicity, and cardiovascular diseases (CVDs), can disrupt the balance between muscle protein synthesis and degradation, leading to skeletal muscle atrophy. Mitochondrial dysfunction is a major contributing mechanism to skeletal muscle atrophy, as it plays crucial roles in various biological processes, including energy production, metabolic flexibility, maintenance of redox homeostasis, and regulation of apoptosis. In this review, we critically examine recent knowledge regarding the causes of muscle atrophy (disuse, cachexia, aging, etc.) and its contribution to CVDs. Additionally, we highlight the mitochondrial signaling pathways involvement to skeletal muscle atrophy, such as the ubiquitin-proteasome system, autophagy and mitophagy, mitochondrial fission-fusion, and mitochondrial biogenesis. Furthermore, we discuss current strategies, including exercise, mitochondria-targeted antioxidants, in vivo transfection of PGC-1α, and the potential use of mitochondrial transplantation as a possible therapeutic approach.

Intraobserver and interobserver agreement for the interpretation of 68Ga-prostate-specific membrane antigen-I&T positron emission tomography/computed tomography imaging.

OBJECTIVES: The use of Ga-prostate-specific membrane antigen positron emission tomography/computed tomography is spreading due to its clinical benefits. In this study, we aim to determine the intra- and interobserver agreement levels of Ga- prostate-specific membrane antigen-I&T positron emission tomography/computed tomography according to molecular imaging tumor-lymph node-metastases reporting system. MATERIALS AND METHODS: Eighty prostate cancer patients and underwent Ga- prostate-specific membrane antigen positron emission tomography/computed tomography were blindly evaluated twice by four nuclear medicine specialists at intervals of 4 weeks. The evaluations were performed according to molecular imaging tumour-lymph node-metastases (miTNM) classification. We used Cohen's Kappa and Fleiss' Kappa analysis to analyse intra- and interobserver agreements. RESULTS: When Ga-prostate-specific membrane antigen positron emission tomography/computed tomography findings were evaluated according to miTNM classification, the obtained kappa values were as follows. The intraobserver Cohen's kappa coefficient was found to be 0.79 (substantial agreement), 0.93 (almost perfect agreement), and 0.94 (almost perfect agreement) for miT, miN, and miM, respectively. During interobserver evaluation between the four observers, the kappa coefficient was 0.52 (moderate agreement) for miT, 0.74 (substantial agreement) for miN, and 0.84 (almost perfect agreement) for miM. CONCLUSION: There is no research on the intraobserver agreement analysis of Ga-prostate-specific membrane antigen positron emission tomography/computed tomography in the literature. Our findings are the first ones. The intraobserver agreement was almost perfect. Moreover, although Ga-prostate-specific membrane antigen I&T positron emission tomography/computed tomography had moderate interobserver evaluation compliance of the primary tumour, it had excellent interobserver agreement levels in local lymph node metastasis and distant metastasis evaluation.4012501255.