土田 邦博

Salt stress severely limits wheat growth and seed yield; however, the mechanisms underlying plant-derived smoke (PDS)-induced salt tolerance remain unclear. The present study performs membrane proteomics to clarify how PDS solution enhances salt tolerance in wheat. Immunoblot analysis of subcellular marker proteins confirms successful enrichment of membrane fractions. Principal component analysis shows that 200 mM NaCl markedly alters membrane-protein composition in wheat roots, whereas 2000 ppm PDS solution largely restores these changes even under salt stress. At the protein level, mitochondrial ascorbate peroxidase increases in roots under salt stress but decreases with PDS-solution treatment, while leaves show the opposite trend. Salt stress reduces ATP content and H+-ATPase abundance; PDS-solution treatment restores both to near-control levels. In contrast, aquaporin levels increase under salt stress but decline after PDS-solution application. In addition, the expression of ammonium transporter was downregulated significantly under salt stress but recovered with PDS-solution treatment. These results suggest that PDS solution may confer salt-stress tolerance to wheat by regulating energy metabolism, water permeability, and ammonium absorption in the root membrane.

BACKGROUND: Salinity, which hampers wheat growth and development, is one of the major abiotic stresses. Plant-derived smoke (PDS) solution alleviates salt stress and promotes wheat growth and development; however, the underlying molecular mechanisms have not been completely clarified. METHODS: In this study, nuclear proteomics was employed to reveal the promotive effect of PDS solution on salt-stressed wheat. Nuclear fractions were isolated from wheat roots, and their purity was confirmed via enrichment of histone H3 and reduction of cytosolic ascorbate peroxidase. Using this nuclear purification technique, label-free nano LC-MS/MS-based nuclear proteomics was performed to identify differentially abundant nuclear proteins in salt-stressed wheat with or without PDS solution treatment. RESULTS: Salt stress decreased histone H2A and DNA polymerase levels, whereas PDS solution treatment of salt-stressed wheat increased levels of histone variants (H2A, H2B, H3, and H4), DNA polymerase, and DNA topoisomerase II. In addition, the PDS solution increased the levels of pre-mRNA cleavage factor Im 25 kDa subunit and RNA helicase in salt-stressed wheat. Immunoblot analysis further validated the increase in histone deacetylase levels triggered by the PDS solution treatment in the salt-stressed wheat. CONCLUSIONS: These results suggest that PDS solution alters nuclear proteins in a way that contributes to chromatin remodeling and transcription during salt stress.

Inducing fast myofiber programs offers therapeutic potential for skeletal muscle disorders such as sarcopenia, where fast myofibers are preferentially lost. Engineered muscle-specific AAV (MyoAAV) vectors enable efficient transduction of skeletal muscles after systemic administration; however, cardiac transgene expression limits applications requiring skeletal muscle-selective delivery. We generated modified MyoAAV vectors by incorporating cardiac-specific miR-208a target sequences into the transgene 3′UTR. This design markedly suppressed cardiac expression while preserving skeletal muscle output, with target-site variation enabling tunable trade-offs between cardiac detargeting and skeletal muscle expression levels. We validated this platform using neural retina leucine zipper (Nrl), a large Maf transcription factor regulating type IIb myofiber identity. Systemic delivery of conventional MyoAAV-Nrl caused severe cardiac hypertrophy and uniform lethality within one month. Conversely, incorporating miR-208a target sequences prevented detectable hypertrophy and eliminated mortality during the experimental observation period. This modification significantly reduced cardiac Nrl expression while maintaining skeletal muscle levels, successfully promoting type IIb myofiber formation and hypertrophy across multiple skeletal muscles. These findings demonstrate that miR-208a-mediated cardiac detargeting combined with MyoAAV-Nrl enables safe systemic induction of fast myofiber remodeling and hypertrophy, establishing a platform for gene therapies targeting skeletal muscle disorders associated with fast myofiber loss.

This review summarizes recent advances in ligand trap therapies targeting activin type II receptors [ActRIIA/ACVR2A and ActRIIB/ACVR2B], which serve as shared receptors for members of the TGF-β family, including activins, GDF11, and myostatin [MSTN]. These receptors mediate Smad2/3 signaling and play critical roles in hematopoiesis, vascular homeostasis, and muscle regulation. Two peptide-based ligand traps have recently received clinical approval: luspatercept [ActRIIB-Fc], an erythroid maturation agent, and sotatercept [ActRIIA-Fc], a novel therapeutic agent for pulmonary arterial hypertension [PAH]. Luspatercept primarily inhibits activin B and GDF11, thereby promoting late-stage erythropoiesis and demonstrating efficacy in anemia associated with conditions such as myelodysplastic syndromes [MDS] and β-thalassemia. Sotatercept binds activins and GDFs to rebalance Smad2/3 and Smad1/5/8 signaling, thereby improving vascular remodeling in PAH. Although both agents have failed to increase skeletal muscle mass in clinical trials consistently, they represent significant advances in the treatment of hematopoietic and vascular disorders. Future studies should focus on optimal dosing strategies, long-term safety, and potential synergistic effects when combined with other therapeutic modalities.