Myocardial fibrosis is a significant pathological basis of heart failure. Overactivation of the ERK1/2 and JNK1/2 signaling pathways of MAPK family members synergistically promotes the proliferation of myocardial fibroblasts and accelerates the development of myocardial fibrosis. In addition to some small molecule inhibitors and Western drugs, many Chinese medicines can also inhibit the activity of ERK1/2 and JNK1/2, thus slowing down the development of myocardial fibrosis, and are generally safe and effective. However, the specific biological mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis still need to be fully understood, and there is no systematic review of existing drugs and methods to inhibit them from improving myocardial fibrosis. This study aims to summarize the roles and cross-linking mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis and to systematically sort out the small-molecule inhibitors, Western drugs, traditional Chinese medicines, and non-pharmacological therapies that inhibit ERK1/2 and JNK1/2 to alleviate myocardial fibrosis. In the future, we hope to conduct more in-depth research from the perspective of precision-targeted therapy, using this as a basis for developing new drugs that provide new perspectives on the prevention and treatment of heart failure.

Coronary microvascular dysfunction (CMD) is a high-risk factor for a variety of cardiovascular events. Due to its complex aetiology and concealability, knowledge of the pathophysiological mechanism of CMD is still limited at present, which greatly restricts its clinical diagnosis and treatment. Studies have shown that CMD is closely related to a variety of cardiovascular diseases, can aggravate the occurrence and development of cardiovascular diseases, and is closely related to a poor prognosis in patients with cardiovascular diseases. Improving coronary microvascular remodelling and increasing myocardial perfusion might be promising strategies for the treatment of cardiovascular diseases. In this paper, the pathogenesis and functional assessment of CMD are reviewed first, along with the relationship of CMD with cardiovascular diseases. Then, the latest strategies for the treatment of CMD and cardiovascular diseases are summarized. Finally, urgent scientific problems in CMD and cardiovascular diseases are highlighted and future research directions are proposed to provide prospective insights for the prevention and treatment of CMD and cardiovascular diseases in the future.

Focusing on cardiomyocyte survival in the prevention and treatment of heart failure, ferroptosis and pyroptosis-two vital modes of cell death-have attracted intense interest. The immunomodulatory cGAS/STING axis, a currently prominent pathway, has also been found to mediate both ferroptosis and pyroptosis; however, the underlying mechanisms remain unclear. This review first traces the historical development of ferroptosis and pyroptosis, dissecting their distinctions, interconnections, and molecular biology. It then spotlights the cGAS/STING axis, elucidating the structural hallmarks of its core proteins, the cascade of signal activation and propagation, its self-amplifying feedback loop, and the precise routes through which it orchestrates ferroptosis and pyroptosis, while also revealing how these two death modalities in turn reinforce the pathway. Furthermore, we investigate the combined effects of ferroptosis and pyroptosis on cardiac structure and function, and rigorously evaluate emerging therapeutic strategies targeting the cGAS/STING axis, encompassing chemical drugs, bioactive natural compounds, small-molecule antagonists, genetic interventions, and exercise training. By integrating the axis's dual role in counteracting pyroptosis and ferroptosis, the review highlights the cGAS/STING pathway as a central target in heart failure management, offering insights to advance both theoretical frameworks and practical therapeutic avenues.

Purpose. Fushen Granule (FSG) is a Chinese medicine prepared by doctors for treating patients with chronic renal failure, which is usually accompanied by gastrointestinal dysfunction. Here, we explore the protective effect of FSG on intestinal barrier injury in chronic renal failure through bioinformatic analysis and experimental verification. Methods. In this study, information on the components and targets of FSG related to CRF is collected to construct and visualize protein-protein interaction networks and drug-compound-target networks using network pharmacological methods. DAVID is used to conduct gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, it is validated by in vitro experiments. In this study, the human intestinal epithelial (T84) cells are used and divided into four groups: control group, model group, FSG low-dose group, and FSG high-dose group. After the experiment, the activity of T84 cells is detected by a MTT assay, and the expressions of tight junction protein ZO-1, claudin-1, nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) are examined by immunofluorescence and/or western blotting. Results. Eighty-six potential chronic renal failure-related targets are identified by FSG; among them, nine core genes are screened. Furthermore, GO enrichment analysis shows that the cancer-related signaling pathway, the PI3K-Akt signaling pathway, the HIF1 signaling pathway, and the TNF signaling pathway may play key roles in the treatment of CRF by FSG. The MTT method showed that FSG is not cytotoxic to uremic toxin-induced injured T84 cells. The results of immunofluorescence and WB indicate that compared with the control group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is decreased and protein expressions level of HO-1, MDA, and COX-2 is increased after urinary toxin treatment. Instead, compared with the model group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is increased and protein expressions level of HO-1, MDA, and COX-2 is decreased after FSG treatment. Conclusion. FSG had a protective effect on urinary toxin-induced intestinal epithelial barrier injury in chronic renal failure, and its mechanism may be related to the upregulation of Nrf2/HO-1 signal transduction and the inhibition of tissue oxidative stress and inflammatory responses. Screening CRF targets and identifying the corresponding FSG components by network pharmacological methods is a practical strategy to explain the mechanism of FSG in improving gastrointestinal dysfunction in CRF.