One of the causes of sarcopenia is that homeostasis between anabolism and catabolism breaks down due to muscle metabolism changes. Rutin has shown antioxidant and anti-inflammatory effects in various diseases, but there are few studies on the effect on muscle loss with aging. The effect of rutin on muscle loss was evaluated using dexamethasone-induced muscle loss C2C12 myoblast and mouse model. In the group treated with dexamethasone, the muscle weight of gastrocnemius (GA), tibialis anterior (TA), and extensor digitorum longus (EDL) in the mouse model were significantly decreased (p < 0.0001 in GA, p < 0.0001 in TA, and p < 0.001 in EDL) but recovered (p < 0.01 in GA, p < 0.0001 in TA, and p < 0.01 in EDL) when treated with rutin. MAFbx, MuRF1, and FOXO3 protein expression of C2C12 myoblast were significantly increased (p < 0.01 in MAFbx, p < 0.01 in MuRF1, and p < 0.01 in FOXO3) when treated with dexamethasone, but it was recovered (p < 0.01 in MAFbx, p < 0.01 in MuRF1, and p < 0.01 in FOXO3) when rutin was treated. In addition, MAFbx and FOXO3 protein expression in GA of mouse model was significantly increased (p < 0.0001 in MAFbx and p < 0.001 in FOXO3) when treated with dexamethasone, but it was also recovered (p < 0.01 in MAFbx and p < 0.001 in FOXO3) when rutin was treated. The present study shows that rutin blocks the FOXO3/MAFbx and FOXO3/MuRf1 pathways to prevent protein catabolism. Therefore, rutin could be a potential agent for muscle loss such as sarcopenia through the blocking ubiquitin-proteasome pathway associated with catabolic protein degradation.

Skeletal muscle is increasingly recognized as a dynamic endocrine and paracrine organ that communicates with distal tissues through a diverse secretome of peptides, proteins, metabolites, and extracellular vesicles (EVs), collectively referred to as myokines and exerkines. Beyond cataloging individual factors, emerging evidence suggests that muscle-derived signals can convey information through an integrated, context-dependent “endocrine code”—a pattern defined by secretion kinetics, co-released signal combinations, delivery modalities, and target-tissue receptor landscapes. This review synthesizes current evidence on (i) conceptual and experimental criteria for defining bona fide myokines, (ii) mechanisms governing myokine expression, processing, and release across exercise modes and physiological states, and (iii) major muscle–organ axes that connect physical activity to systemic metabolic homeostasis, immune remodeling, tissue regeneration, and neurocognitive adaptation. We further discuss non-protein mediators such as lactate, succinate, and β-aminoisobutyric acid, and highlight EVs as a multiplexed delivery modality whose interpretation requires stringent isolation, contamination controls, and functional validation. Finally, we evaluate translational opportunities—including biomarker panels, therapeutic targeting of the myostatin/activin, fibroblast growth factor 21 (FGF21), and growth differentiation factor 15 (GDF15) pathways, and precision exercise prescriptions informed by multi-omics and artificial intelligence—while emphasizing analytical standardization, causal validation, and transparent reporting as prerequisites for clinical impact.

Glucocorticoid therapy, using agents like dexamethasone (Dexa), often leads to muscle atrophy by increasing protein degradation via the ubiquitin–proteasome system while suppressing protein synthesis. Stigmasterol, a phytosterol with known bioactivities, has an unexplored role in muscle atrophy. This study investigated stigmasterol’s protective effects against Dexa-induced muscle atrophy and its impact on the FoxO3 and mTORC1 signaling pathways. Differentiated C2C12 myotubes were treated with Dexa (50 µM) ± stigmasterol (10 µM), and the morphology, viability, and protein levels in the FoxO3/MuRF1/MAFbx catabolic and mTOR/p70S6K/4E-BP1 anabolic signaling pathways were assessed. C57BL/6 mice received Dexa (20 mg/kg/day i.p.) ± stigmasterol (3 mg/kg/day oral) for 21 days, and the body/muscle mass, bone mineral density (BMD), fiber cross-sectional area (CSA), and muscle protein expression were measured. Stigmasterol (10 µM) was non-toxic and attenuated Dexa-induced reductions in myotube diameter and fusion in vitro, concurrent with suppressing Dexa-induced upregulation of FoxO3/MuRF1/MAFbx proteins and preventing the Dexa-induced dephosphorylation of mTOR/p70S6K/4E-BP1 proteins. In vivo, stigmasterol mitigated Dexa-induced losses in body weight, muscle mass, BMD, and fiber CSA. This protection was associated with attenuated upregulation of FoxO3 and MAFbx proteins in muscle tissue. Stigmasterol protected against Dexa-induced muscle atrophy in vitro and in vivo via modulation of the FoxO3–MAFbx catabolic pathway. These findings suggest stigmasterol inhibits excessive glucocorticoid-induced muscle protein breakdown. It therefore warrants further investigation as a potential therapeutic agent for glucocorticoid myopathy.

Drug resistance is a major cause of treatment failure in breast cancer, yet mutation-centered models do not fully explain delayed resistance, reversible tolerance, or re-sensitization after treatment interruption. Here, we synthesize recent findings in drug-tolerant persister (DTP) biology, clonal evolution, and tumor ecosystem dynamics to propose a breast cancer-focused Resistance Continuum as a conceptual framework for organizing the transition from initial therapy to stable resistance across ER-positive, HER2-positive, and triple-negative disease. Here, we synthesize recent findings in drug-tolerant persister (DTP) biology, clonal evolution, and tumor ecosystem dynamics to propose a breast cancer-focused Resistance Continuum as a conceptual framework for organizing the transition from initial therapy to stable resistance across ER-positive, HER2-positive, and triple-negative disease. This framework describes a canonical, but not universal, trajectory spanning treatment-naïve heterogeneity, pre-adaptive priming, reversible DTP states, cycling persisters, and genetically stabilized resistant clones. We discuss how epigenetic and metabolic plasticity may sustain persistence, and we present epigenetic memory as an emerging hypothesis linking repeated non-genetic persistence to facilitated resistance in selected contexts. We also compare subtype-specific features of DTP biology, outline a multi-omics roadmap for interrogating the continuum, and highlight therapeutic opportunities for resistance interception. Overall, the Resistance Continuum is intended as a working scaffold to integrate current evidence and guide future mechanistic and translational studies.

Lee JK, et al. Ann Surg Treat Res. 2023 Dec;105(6):385-395. https://doi.org/10.4174/astr.2023.105.6.385

We report considerations related with surgery through 2 cases of acute apendicitis with COVID-19 infection. In November and December 2020, two patients infected with COVID-19 developed acute apendicitis and underwent emergency surgery. In case 1, an 84-year-old woman was asymptomatic and diagnosed with acute apendicitis on the 20th day of infection. She was discharged after surgery without complication. In contrast, case 2 was a 69-year-old male patient with pneumonia treated with antibiotics, steroids and remdesivir. After surgery, he was hospitalized for a long duration due to persistent pneumonia and wound complications. We should perform appendectomy in well-established negative pressure operating rooms, personal protective equipment, and protocols. Since the physical examination and blood tests were limited, image examination like computed tomography scan should be considered if acute apendicitis is suspected. If the patient has pneumonia before surgery, it can get worse after surgery, and complications such as wound infections can occur.