Myosin cross-bridges dissociate from actin following Mg²⁺-adenosine triphosphate (MgATP) binding. Myosin hydrolyses MgATP into inorganic phosphate (P_i) and Mg²⁺-adenosine diphosphate (ADP), and release of these hydrolysis products drives chemo-mechanical energy transitions within the cross-bridge cycle to power muscle contraction. Some forms of heart disease are associated with metabolic or enzymatic dysregulation of the MgATP-MgADP nucleotide pool, resulting in elevated cytosolic [MgADP] and impaired muscle relaxation. We investigated the mechanical and structural effects of increasing [MgADP] in permeabilized myocardial strips from porcine left ventricle samples. Sarcomere length was set to 2.0 µm at 28 °C, and all solutions contained 3% dextran T-500 to compress myofilament lattice spacing to near-physiological values. Under relaxing low [Ca²⁺] conditions (pCa 8.0, where pCa = −log₁₀[Ca²⁺]), tension increased as [MgADP] increased from 0-5 mM. Complementary small-angle X-ray diffraction measurements show that the equatorial intensity ratio, I_1,1/I_1,0, also increased as [MgADP] increased from 0 to 5 mM, indicating myosin head movement away from the thick-filament backbone towards the thin-filament. Ca²⁺-activated force-pCa measurements show that Ca²⁺-sensitivity of contraction increased with 5 mM MgADP, compared to 0 mM MgADP. These data show that MgADP augments tension at low [Ca²⁺] and Ca²⁺-sensitivity of contraction, suggesting that MgADP destabilizes the quasi-helically ordered myosin OFF state, thereby shifting the cross-bridge population towards the disordered myosin ON state. Together, these results indicate that MgADP enhances the probability of cross-bridge binding to actin due to enhancement of both thick and thin filament-based activation mechanisms.

Chronic atrophic gastritis (CAG) is a pivotal precancerous condition in gastric carcinogenesis, with progression typically following the classic Correa cascade. Although Helicobacter pylori (H. pylori) infection is widely recognized as the principal etiological factor, the persistence of gastric cancer (GC) risk in a subset of patients after successful eradication suggests that gastric microbiota dysbiosis may also contribute to CAG progression. In recent years, high-throughput sequencing technologies have revealed distinct microbial restructuring in patients with CAG, characterized by decreased microbial diversity, depletion of commensal taxa, and enrichment of opportunistic pathogens. These compositional changes are accompanied by metabolic dysfunction, activation of inflammatory signaling pathways, and disruption of immune homeostasis, which may contribute to a microenvironment permissive for precancerous transformation of the gastric mucosa. Probiotics and related microbiome-based therapeutics, including prebiotics, synbiotics, and postbiotics, have emerged as promising adjunctive strategies for H. pylori eradication and disease management. Their beneficial effects are mediated through multiple mechanisms, including remodeling of the microbial community, inhibition of pathogen colonization, modulation of host immune responses, and restoration of mucosal barrier integrity. However, whether these interventions can reverse established atrophic or metaplastic lesions remains unclear. In addition, how strain specificity, dose dependency, and interindividual heterogeneity influence clinical efficacy has yet to be fully elucidated. In this review, we summarize the compositional and functional features of gastric microbiota dysbiosis in patients with CAG, as well as the mechanisms and clinical applications of microbiome-based interventions. We further highlight current limitations in the field and discuss future directions for precision microecological therapies integrating multi-omics approaches, engineered probiotics, and artificial intelligence. These advances may provide a theoretical framework and practical guidance for the diagnosis and management of CAG and the prevention of GC.

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease associated with gut microbiota dysbiosis. The triple-probiotic mixture BLE (Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis) contains highly oxygen-sensitive strains prone to viability loss during gastrointestinal transit. Adding facultative-aerobic Bacillus cereus generates a four-strain probiotic formulation BLEB. This study aimed to determine whether adding B. cereus improves the anti-colitis capacity of BLE and explore the underlying microbiota–spermidine-related regulatory mechanism. Methods: Acute dextran sulfate sodium (DSS)-induced colitis mouse models were applied to compare the therapeutic effects of BLE and BLEB. We evaluated disease phenotype, intestinal epithelial barrier integrity, and splenic Treg/Th17 immune homeostasis. Dynamic 16S rRNA sequencing and untargeted intestinal metabolomics characterized gut microbial and metabolic alterations, with Spearman correlation for microbiota–metabolite association analysis. Transcriptomic profiling was performed on DSS-injured Caco-2 cells to examine molecular responses to spermidine. Results: BLEB exerted superior dose-dependent anti-colitis effects compared with BLE. BLEB enriched beneficial Lactobacillaceae and restored luminal polyamine metabolites including spermidine. Spearman correlation revealed significant positive correlations between Lactobacillaceae-affiliated genera and polyamine levels. In vitro, spermidine reversed DSS-provoked transcriptional perturbations and upregulated the transcription of glutathione-centered antioxidant-related genes in Caco-2 cells. Conclusions: Ecological synergy introduced by B. cereus may reshape gut microbiota and increase microbiota-related spermidine, partially contributing to the enhanced mucosal protection conferred by BLEB. This work provides pre-clinical evidence supporting the development of aerobic–anaerobic combined probiotic cocktails for auxiliary UC therapy.