therapeutics
Heme Metabolism-Derived Carbon Monoxide Regulates Skeletal Muscle Function.
BACKGROUND
Heme oxygenases, HO-1 (Hmox1) and HO-2 (Hmox2), regulate skeletal muscle homeostasis by degrading heme and generating carbon monoxide (CO), a bioactive signalling molecule. Although HO-1 is known to influence muscle fibre composition and mitochondrial function, the role of HO-2 in...
Why Osteosarcopenia Matters: Clinical and Investigative Implications.
BACKGROUND
Osteosarcopenia, the combination of osteoporosis and sarcopenia, is a geriatric syndrome linked to functional decline, falls, and fragility fractures. The interaction among bone, muscle, and their shared pathophysiology is driven by mechanical, metabolic, and hormonal factors. With global population aging...
Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti-GDF-15 Antibody-Based Combination Therapies.
BACKGROUND
In a recent Phase 2 trial in patients with cancer cachexia, the anti-GDF-15 antibody ponsegromab resulted in increased body weight, appetite, muscle mass and physical activity. This study provides compelling evidence that targeting the GDF-15 pathway may offer a viable...
Differential Branched-Chain Amino Acid Metabolism in Tissues of Tumor-Bearing Male Mice.
Cancer cachexia is a multifactorial syndrome characterized by involuntary loss of skeletal muscle and adipose tissue that is often resistant to nutritional support. The branched-chain amino acids (BCAA: leucine, isoleucine, and valine) stimulate protein synthesis, yet BCAA-targeted therapies have yielded...
GDF10 exacerbates metastatic burden and cachexia in murine models of cancer.
Metastasis and cancer-induced cachexia significantly reduce survivorship and quality of life for cancer patients. GDF10 (BMP3b) is a TGF-ß superfamily ligand with little knowledge of its role in cancer progression. Some studies have shown that GDF10 exerts tumor-suppressive effects in...
De novo and scaffold-based design of GDF15 binders for cancer cachexia diagnostics and therapeutics.
Growth differentiation factor-15 (GDF15), a stress-responsive cytokine of the transforming growth factor-β superfamily, is elevated in cancer cachexia, chemotherapy-induced nausea, and hyperemesis gravidarum, making it both a biomarker and a therapeutic target. Here, we developed high-affinity GDF15 binders using an...
Development of High-Affinity Ligands for Human UBR2.
UBR box-containing ubiquitin E3 ligases recognize the N-termini of their target proteins through the UBR box, and a member of the family, UBR2, has been established as a target to treat cancer- and diabetes-associated cachexia. However, the development of high-affinity...
Effectiveness and Safety of Interventions for Sarcopenia in Advanced Prostate Carcinoma: Systematic Review.
BACKGROUND
Sarcopenia has emerged as a potential prognostic factor in patients with advanced prostate cancer (PCa), requiring interventions for its prevention and treatment.
OBJECTIVE
We aimed to systematically identify, critically assess and synthesize the available evidence on the effectiveness and safety of interventions...
Micheliolide ameliorates colon cancer cachexia by modulating gut microbiota-immune signaling via Phocaeicola vulgatus enrichment.
BACKGROUND
Cancer cachexia profoundly impacts patient survival and quality of life. Current treatments fail to halt this trajectory, highlighting an urgent clinical need for host-directed therapies capable of uncoupling skeletal muscle wasting from tumor progression. This study investigated the therapeutic potential...
Sarcopenia in Patients With Cancer and Its Association With Chemotherapy-Induced Peripheral Neurotoxicity.
BACKGROUND AND OBJECTIVES
Chemotherapy-induced peripheral neurotoxicity (CIPN) is the most common neurologic complication of cancer treatment. Sarcopenia, characterized by muscle mass loss, has been associated with treatment-related toxicity, but its association with CIPN remains unclear. We aimed to assess the association...
Biosacetalin (1,1-Diethoxyethane) Prolongs Survival and Alleviates Cachexia in the NSG Mice Bearing Neuroblastoma SH-SY5Y Cells.
Neuroblastoma remains a formidable pediatric malignancy characterized by profound metabolic plasticity and limited therapeutic responsiveness in high-risk disease. Emerging evidence positions the interplay between Reactive Oxygen Species (ROS) and the metabolic sentinel AMP-activated protein kinase (AMPK) as a critical regulator...
Juyuanjian attenuates sarcopenia through dual regulation of the Akt/FoxO1 and SIRT1/PGC-1α pathways.
BACKGROUND
Sarcopenia, an age-related degenerative disease, corresponds to "Qi Xu" syndrome in traditional Chinese medicine. Juyuanjian (JYJ), a classical Qi-tonifying formula, has shown potential against muscle atrophy and functional decline, but its molecular mechanisms are not well understood.
PURPOSE
To investigate whether JYJ...
Cancer cachexia induces senescent reprogramming of brown adipose tissue and pro-cachectic S100A9 secretion by adipocytes.
Cancer-associated cachexia (CAC) is a multifactorial wasting syndrome characterized by progressive loss of fat and lean mass, systemic inflammation, and poor therapeutic responsiveness. While brown adipose tissue (BAT) is traditionally considered a protective, energy-dissipating organ, its qualitative remodeling in CAC...
Elevated Circulating Ceramides 18:0 and 24:1 as a Risk Factor for Sarcopenia: In Vitro, Animal, and Clinical Evidence.
BACKGROUND
Ceramides have garnered considerable attention as pro-aging bioactive lipids implicated in both metabolic dysfunction and musculoskeletal decline. Among these, C18:0 and C24:1 ceramides may play a role in the pathophysiology of sarcopenia, a key manifestation of age-related deterioration. However, their...
The pathology and diagnosis of cancer cachexia and a treatment insight from natural products: A review.
Cancer cachexia, which is characterized by weight loss and muscle wasting with or without fat depletion, is a complex syndrome that commonly seen in patients with advanced cancer. The underlying pathophysiological mechanisms of cancer cachexia involve in systemic inflammation, abnormal...
