Guangxi University of Chinese Medicine

Myocardial ischemia-reperfusion injury (MIRI) presents significant clinical challenges due to its complex multimechanistic pathophysiology. Although hydrogen sulfide (H₂S) and carbon monoxide (CO) exhibit individual cardioprotective effects via anti-apoptotic/anti-inflammatory pathways, their synergistic potential remains underexplored due to the absence of delivery systems enabling spatiotemporal co-regulation of these gasotransmitters. Current approaches face technical limitations in simultaneous gas quantification and therapeutic delivery, often compromising treatment efficacy through gas leakage during monitoring. To address these challenges, we developed HSCOD, a theranostic donor featuring cysteine-activated H₂S release followed by light-controlled CO generation, while incorporating self-reporting fluorescence for real-time gas tracking. In cellular and zebrafish MIRI models, dual-gas co-delivery demonstrated superior efficacy to monotherapies, significantly reducing apoptosis, pyroptosis, oxidative stress, and inflammation through coordinated cardioprotection. This study further validated the "gas waltz therapy" concept of spatiotemporally orchestrated gas interactions, with HSCOD serving as both a therapeutic agent and research tool for decoding gas crosstalk in multifactorial diseases. The platform overcomes critical limitations in gas therapy by integrating controlled release with real-time tracking, advancing targeted treatment strategies for complex pathologies.

Osteoporosis (OP) is a skeletal disease prevalent among middle-aged and elderly populations. Although traditional Chinese medicine (TCM) has demonstrated notable efficacy in treating OP, systematic studies remain scarce, and the core medicinal herbs and their mechanisms of action against OP are still unclear. This study employed data mining techniques to identify commonly prescribed clinical herbs for OP, investigated their potential mechanisms of action using network pharmacology, and subsequently validated these findings experimentally.

A total of 239 clinical prescriptions for OP treatment were collected from hospitals in Guangxi, Suzhou, and other regions, from which frequently used medicinal herbs were identified through data mining. Osteoporosis-related target data were retrieved from databases, and potential core therapeutic targets were identified by intersection analysis. Protein-protein interaction (PPI) networks were built based on the STRING database and subsequently subjected to topological analysis. Enrichment analysis of intersecting targets was conducted with R software to screen for the key signaling pathways and target proteins involved in TCM treatment of OP, and the predictive results were experimentally validated.

A total of 239 prescriptions involving 164 medicinal herbs were included, with 10 herbs showing strong associations primarily characterized by sweet taste and warm properties. One hundred and one potential targets of Yishen Gushu Formula (YSGSF) for OP treatment were identified. The primary bioactive compounds identified included Quercetin, Kaempferol, and Luteolin. KEGG enrichment analysis highlighted signaling pathways such as the Toll-like receptor, Estrogen signaling pathway. Molecular docking indicated strong interactions between these key targets and the potential active components, which were further validated experimentally.

This study found that the core compound YSGSF in the TCM formula for the treatment of OP primarily exerts its effects by targeting molecules such as JUN, FOS, ESR1, AKT1, and MAPK3. These effects are mediated through the modulation of signal pathways, including the Toll-like receptor, TNF, and Estrogen pathways, which increase bone mineral density, improve osteocyte morphology, and enhance trabecular bone structure. The high-dose formula treatment promotes a BMD increase of approximately 6.94 %, thereby improving the therapeutic efficacy in treating OP.

Rheumatoid arthritis (RA) is an autoimmune condition that causes joint damage and persistent synovial inflammation. Recent research has demonstrated the critical roles that fibroblastic synoviocytes (FLS) autophagy abnormalities, hypoxia inducible factor (HIF) signaling activation, and aberrant production of inflammatory factors play in the pathophysiology of RA. Although kaempferol is a naturally occurring flavonoid with anti-inflammatory, antioxidant, and other biological properties, it is yet unknown how it controls FLS autophagy in RA.

To screen for autophagy-associated core genes, this study used transcriptome data related to RA in conjunction with weighted gene co-expression network analysis (WGCNA) and LASSO regression. The function of immune cells in RA lesions was investigated in conjunction with immune infiltration research, and in vitro cell tests confirmed kaempferol's regulatory effect on important genes.

Through screening, 8 key genes that are intimately linked to RA autophagy were found. In addition to IL-17 signaling and aberrant mitochondrial autophagy, it was discovered that the HIF signaling pathway was highly activated in RA synovial cells, which promoted inflammatory responses and aberrant cell proliferation. Significant neutrophil and macrophage aggregation was revealed by immune infiltration studies, aggravating inflammation and hypoxia in synovial tissue. Kaempferol controlled the expression of key genes such HIF1A, MYC, and HMOX1, enhanced mitochondrial activity, and dramatically reduced the proliferation of FLS, according to cell tests.

This study reveals the molecular mechanism of autophagy imbalance in FLS in RA, emphasizes the synergistic effect of HIF-IL17 mitochondrial autophagy pathway, and clarifies the potential of kaempferol to exert therapeutic effects by regulating this pathway, providing new ideas for targeted therapy of RA.