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Skeletal muscle is increasingly recognized as a dynamic endocrine organ whose secretome—particularly myokines—serves as a central hub for the coordination of systemic metabolic health, inflammation, and tissue adaptation. This review integrates molecular, cellular, and physiological evidence to elucidate how myokine signaling translates mechanical and metabolic stimuli from exercise into biochemical pathways that regulate glucose homeostasis, lipid oxidation, mitochondrial function, and immune modulation. We detail the duality and context-dependence of cytokine and myokine actions, emphasizing the roles of key mediators such as IL-6, irisin, SPARC, FGF21, and BAIBA in orchestrating cross-talk between muscle, adipose tissue, pancreas, liver, bone, and brain. Distinctions between resistance and endurance training are explored, highlighting how each modality shapes the myokine milieu and downstream metabolic outcomes through differential activation of AMPK, mTOR, and PGC-1α axes. The review further addresses the hormetic role of reactive oxygen species, the importance of satellite cell dynamics, and the interplay between anabolic and catabolic signaling in muscle quality control and longevity. We discuss the clinical implications of these findings for metabolic syndrome, sarcopenia, and age-related disease, and propose that the remarkable plasticity of skeletal muscle and its secretome offers a powerful, multifaceted target for lifestyle interventions and future therapeutic strategies. An original infographic is presented to visually synthesize the complex network of myokine-mediated muscle–organ interactions underpinning exercise-induced metabolic health.

30 October 2025

Myokines: A Symphony of “Sarcosignalling”. Artistic representation of the complex network of myokines and their relationships with cellular pathways, energy metabolism, the inflammasome, and tissue remodelling. Representation shows skeletal muscle as an endocrine hub that converts mechanical work and energetic stress into a coordinated secretome of myokines (for example, IL 6, IL 15, irisin, BAIBA, SPARC, FGF21, and Metrnl) which signal locally and systemically to adipose tissue, liver, bone, pancreas, vasculature, and brain to improve fuel partitioning, organ function, immune system competence, restrain inflammation and guide tissue recovery post-exertion. Acute contractions elicit transient ROS that act as hormetic cues, activating AMPK–SIRT1/3–PGC 1α and Nrf2 pathways to drive mitochondrial biogenesis, antioxidant capacity, fatty acid oxidation, and GLUT4 trafficking, while chronic inflammatory nodes (NF κB and NLRP3) are suppressed by the anti-inflammatory myokine milieu to restore insulin sensitivity and counter cellular aging mechanisms. ET loads bias IL 6, irisin, BAIBA, and FGF21 responses to support oxidative remodelling and adipose browning, whereas RET loads accent IL 15, follistatin, decorin, and SPARC to favour hypertrophy and matrix quality; both converge on healthier mitochondria, redox balance, and multi-organ metabolic resilience shown by the cross-organ arrows. Arrow keys: Stimulatory interaction: solid arrowheads indicate activation, upregulation, or a positive causal link between nodes (for example, IL 6 → AMPK; AMPK → PGC 1α; PGC 1α → mitochondrial biogenesis). Inhibitory interaction: blunt, bar-ended lines indicate repression, downregulation, or antagonism (for example, myostatin ┤ protein synthesis; NLRP3/IKK–NF κB ┤ insulin signaling; follistatin ┤ myostatin).

Background/Objectives: Ginsenosides, one of the most pharmaceutically valuable chemical compounds in Panax ginseng, are synthesized with several enzymes, including UGTs. UGTs determine absorbability and physiological function upon consumption. Thus, understanding the functional residues of ginsenoside biosynthesis-associated UGTs is crucial for enhancing the production of valuable ginsenoside varieties. Methods: We collected the UGT homologs of high sequence similarity from two rate-limiting steps of the biosynthetic pathway. The 3D structures of these proteins were predicted using the AlphaFold3 model. The ligand-binding interactions of these UGTs were examined using SwissDock and CB-Dock2. Enzyme kinetics were analyzed with MPEK. Using these tools, we performed in silico mutagenic analyses to identify the functional residues of UGTs in detail. Results: We elucidated the molecular mechanisms of experimentally verified functional residues in UGTs, many of which were associated with optimal ligand interaction angles that expose target carbons. We also identified putatively important amino acid residues that mediate ligand interactions and modulate reaction kinetics by more than 25%. In this study, residues at positions 62, 224, 397, and 398 were shown to significantly influence enzyme kinetics. Conclusions: Our study provides the first structural analysis of the functional residues of ginsenoside biosynthetic UGTs based on their 3D structures. We identified several key amino acid residues essential for proper ginsenoside biosynthesis: (1) residues determining ligand interactions, (2) residues modulating ligand binding angles, and (3) residues affecting reaction kinetics. Our findings demonstrate an effective approach to identifying functional residues in plant enzymes and present valuable UGT candidates for future experimental validation.

14 October 2025

Target reaction and amino acid conservativeness. (A) Schematic diagram presenting UGT-mediated reactions catalyzing PPD and PPT into ginsenoside CK, ginsenoside Rh2, and ginsenoside F1. (B) Amino acid conservativeness plot made by comparing all close homologs.

Therapeutic Strategies Targeting Oxidative Stress and Inflammation: A Narrative Review

  • Charles F. Manful,
  • Eric Fordjour and
  • Emmanuel Ikumoinein
  • + 2 authors

Oxidative stress and inflammation are deeply interconnected processes implicated in the onset and progression of numerous chronic diseases. Despite promising mechanistic insights, conventional antioxidant and anti-inflammatory therapies such as NSAIDs, corticosteroids, and dietary antioxidants have shown limited and inconsistent success in long-term clinical applications due to challenges with efficacy, safety, and bioavailability. This review explores the molecular interplay between redox imbalance and inflammatory signaling and highlights why conventional therapeutic translation has often been inconsistent. It further examines emerging strategies that aim to overcome these limitations, including mitochondrial-targeted antioxidants, Nrf2 activators, immunometabolic modulators, redox enzyme mimetics, and advanced delivery platforms such as nanoparticle-enabled delivery. Natural polyphenols, nutraceuticals, and regenerative approaches, including stem cell-derived exosomes, are also considered for their dual anti-inflammatory and antioxidant potential. By integrating recent preclinical and clinical evidence, this review underscores the need for multimodal, personalized interventions that target the redox-inflammatory axis more precisely. These advances offer renewed promise for addressing complex diseases rooted in chronic inflammation and oxidative stress.

6 October 2025

Cross-talk between NF-κB and Nrf2 signaling pathways.

Background: Cadmium (Cd) pollution poses a significant environmental challenge. Microbially induced carbonate precipitation (MICP), an advanced bioremediation approach, relies on the co-precipitation of soluble metals with the microbial hydrolysate from urea. This study isolated a urease-producing strain and evaluated its Cd remediation potential. Methods: The isolated strain UA7 was identified through 16S rDNA gene sequencing. Urease production was enhanced by optimizing the culture conditions, including temperature, dissolved oxygen levels—which were affected by the rotational speed and the design of the Erlenmeyer flask, and the concentration of urea added. Its Cd remediation efficacy was assessed both in water and soil. Results: UA7 was identified as Lysinibacillus sp., achieving peak urease activity of 188 U/mL. The immobilization rates of soluble Cd reached as high as 99.61% and 63.37%, respectively, at initial concentrations of 2000 mg/L in water and 50 mg/kg in soil. The mechanism of Cd immobilization by strain UA7 via MICP was confirmed by the microstructure of the immobilized products with attached bacteria, characteristic absorption peaks, and the formed compound Ca0.67Cd0.33CO3, which were analyzed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The Cd-remediation effect of strain UA7, which reduces lodging in wheat plants, prevents the thinning and yellowing of stems and leaves, and hinders the transition of soluble Cd to the above-ground parts of the plant, was also demonstrated in a pot experiment. Conclusions: Therefore, Lysinibacillus sp. UA7 exhibited high potential for efficiently remediating contaminated Cd.

2 October 2025

Isolation and identification of urease-producing strains. (A) Color development results of urease agar plates. (B) The phylogenetic tree based on 16S rDNA gene sequences.

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