👤 Jingyu Bo

Post-cardiac surgery anxiety or depression (PCPAD) is a common neuropsychiatric complication following cardiovascular interventional procedures, which significantly increases the risk of adverse cardiovascular events and long-term mortality. Existing treatment strategies have limitations, and clinical needs remain unmet. The gut-brain axis (GBA) serves as a core network regulating neuroimmune and endocrine responses, and its imbalance involves key links such as intestinal flora dysbiosis and neuroimmune crosstalk disorders. It is closely related to the pathogenesis of this complication, providing a novel perspective for targeted interventions. This review aims to systematically clarify the mechanism of GBA in PCPAD, comprehensively explore therapeutic strategies targeting this axis, and focus on the intervention value and application potential of natural products. The study was designed and conducted in strict accordance with the PRISMA 2020 guidelines. Relevant literatures were searched from PubMed, Web of Science Core Collection, ScienceDirect, Embase, Cochrane Library, and CNKI databases from their inception to December 2025. Literatures focusing on GBA-related mechanisms of PCPAD or investigating the mechanisms and clinical applications of natural products targeting GBA for PCPAD treatment were included. Conference abstracts, case reports, duplicate publications, and other ineligible literatures were excluded. Through quality control strategies including double independent screening and verification, priority inclusion of high-credibility evidence, and data cross-validation, 168 eligible literatures were finally included. The composition and functions of GBA, its imbalance mechanisms, and the basic and clinical evidence of natural product-based interventions were systematically analyzed. Studies have shown that GBA imbalance is the core pathogenesis of PCPAD, among which the inflammatory cascade initiated by intestinal flora dysbiosis, abnormal activation of the neuroendocrine axis, disorder of immune-nerve crosstalk, and abnormal gene and epigenetic regulation are key pathological links. In summary, GBA imbalance, especially gut microbiota dysbiosis and neuroimmune interactions, plays a critical role in the pathogenesis of PCPAD. Natural products (including traditional Chinese medicine (TCM) monomers, TCM compound prescriptions, patented TCM drugs, and natural products from other plant sources worldwide) can exert therapeutic effects by synergistically regulating GBA homeostasis through multiple targets. Specifically, they include increasing the abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus, promoting the production of anti-inflammatory metabolites such as short-chain fatty acids, repairing intestinal barrier function, inhibiting pro-inflammatory pathways such as NF-κB and NLRP3 inflammasome, and regulating the levels of neurotransmitters and neurotrophic factors such as 5-HT and BDNF. Basic and clinical studies have confirmed that these natural products have high biocompatibility and low toxic side effects, and are compatible with the safe medication needs of patients during the organ function recovery period after cardiac surgery. Several natural products have been proven to modulate GBA dysfunction, with potential for clinical therapeutic application. This review systematically elucidates a new paradigm of precise intervention for PCPAD via natural products that regulate GBA through multiple targets, addressing the limitation of traditional single-target therapies and providing a low-cost, easily promotable solution for clinical translation. Additionally, natural product-based interventions offer a novel approach for treating post-cardiac surgery complications. In the future, it is necessary to further conduct large-sample, multicenter clinical trials to clarify their mechanisms of action and standardized dosage regimens, strengthen toxicological research, facilitate the translation from basic research to clinical practice, and provide more precise therapeutic strategies for patients. Show less

Atherosclerotic lesions are the fundamental pathologies of cardiovascular diseases. The exact role of the nuclear factor erythroid 2-related factor 2 (NRF2) in macrophages in atherosclerosis remains uncertain. This study aimed to investigate the role of NRF2 in myeloid cells in the development of atherosclerosis. Single-cell RNA sequencing databases were used to explore the expression levels of NRF2 in human and murine atherosclerosis. Plaque areas, necrotic core size, instability index, and efferocytosis in aortic lesions were investigated in myeloid cell-specific Nrf2-knockout mice on an ApoE-deficient background (Nrf2(M)-KO; ApoE NRF2 expression was upregulated in the macrophages of human and murine atherosclerotic arteries compared with their corresponding controls. Nrf2(M)-KO; ApoE Myeloid-specific deletion of Nrf2 promotes inflammation and inhibits macrophage efferocytosis, thereby leading to the aggravation of atherosclerosis. NRF2 activation in macrophages could be a valuable strategy for preventing and treating atherosclerosis. Show less

Metabolic disorders and neurocognitive diseases frequently co-occur, yet the specific mechanisms driving this comorbidity remain elusive. While epidemiological associations are well-documented, the causal links between these conditions are complex and incompletely understood, necessitating a systems-level investigation into their shared biological architecture. This study integrates large-scale human genetics with experimental Network-informed Mendelian randomization identified bidirectional causalities, including a 14% elevated dementia risk from type 2 diabetes and protective effects of obesity against parental Alzheimer's disease (AD). The study identified a signature encompassing key lipid metabolism hubs This multi-modal investigation provides a robust framework that converges on a high-confidence, 13-gene signature of lipid dysregulation as a central mechanistic interface, offering a powerful set of prioritized targets for future functional validation and therapeutic development at the metabolic-neurocognitive nexus. Show less

Cardiac ischemia/reperfusion (I/R) induces systemic oxidative stress, which in turn gives rise to the development of multiple organ abnormalities, including brain injury. The paraventricular nucleus (PVN) of the hypothalamus is a cardiovascular regulatory center. Aerobic exercise is an effective intervention to protect the heart against I/R injury. However, the effect of aerobic exercise on cardiac I/R-induced neuronal injury in the PVN has not been fully elucidated. The aim of this study is to investigate whether aerobic exercise can up-regulate fibroblast growth factor 21 (FGF21) and alleviate neuronal oxidative stress and ferroptosis in the PVN caused by cardiac I/R. In vivo, after six weeks of aerobic exercise, the cardiac I/R model was established by ligating the left anterior descending (LAD) coronary artery for 30 min, followed by 2 h of reperfusion. Cardiac function and heart rate variability (HRV) were measured. Morphological changes, oxidative stress, expression of FGF21 and its downstream signaling molecules, as well as ferroptosis-related indicators in the PVN, were evaluated. In vitro, HT22 cells were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) and treated with recombinant human FGF21 (rhFGF21) and compound C to elucidate the potential mechanism. Cardiac I/R induced iron deposition, elevated expression of lipid peroxidation drivers, and impaired antioxidant capacity in the PVN, which collectively contributed to neuronal ferroptosis. Aerobic exercise up-regulated the expression of FGF21, FGFR1, and PGC-1α, maintained the phosphorylation of AMPKα, enhanced antioxidant capacity, reduced ROS and lipid peroxidation, regulated iron homeostasis, and effectively attenuated neuronal ferroptosis induced by cardiac I/R. In addition, rhFGF21 protected HT22 cells against OGD/R-induced oxidative stress and ferroptosis, which was blocked by AMPK inhibition. FGF21 plays a pivotal role in regulating neuronal oxidative stress and ferroptosis. Aerobic exercise could increase the expression of FGF21, FGFR1, and PGC-1α, maintain the phosphorylation of AMPKα, and alleviate cardiac I/R-induced neuronal oxidative stress and ferroptosis. These results confirm the protective effect of aerobic exercise against cardiac I/R-induced brain injury and provide an experimental basis for studying the relationship between exercise and the "heart-brain axis." Show less

Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity. Show less

The mechanism by which aerobic exercise promotes cardiac function after myocardial infarction (MI) is still not fully understand. In this study, we investigated the role of fibroblast growth factor 21 (FGF21) in exercise protecting the cardiac function of MI mice. In vivo, MI was induced by left anterior descending coronary artery ligation in wild-type and Show less

Chronic apical periodontitis (CAP) is defined as chronic inflammation of the dental pulp and root canal system. Porphyromonas endodontalis lipopolysaccharide ( P. endodontalis LPS) plays an important role in inducing an inflammatory response in CAP. microRNA-146a (miR-146a) is a key regulator of inflammation and is induced by LPS. Hairy and enhancer-of-split related with YRPW motif 2 (Hey2) has been confirmed to be induced by the Notch signaling pathway, which is involved in tooth development, pulp regeneration, and repair after injury. Our study aimed to investigate the functional role of miR-146a via the targeting of Hey2 in CAP as well as the underlying mechanism. Compared with 13 healthy controls, miR-146a and Hey2 expressions were significantly higher in 20 patients with CAP. In addition, miR-146a, Hey2, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α expressions were significantly increased in MC3T3-E1 cells stimulated with different concentrations (0-20 μg/mL) of P. endodontalis LPS for different amounts of time (0-48 hours). Moreover, miR-146a, which acts as an anti-inflammatory mediator, negatively regulated the expression of IL-6, IL-1β, and TNF-α, and Hey2 was confirmed as a target gene of miR-146a by a luciferase reporter assay. Hey2 also negatively regulated miR-146a, IL-6, IL-1β, and TNF-α expressions, and P. endodontalis LPS strongly induced Hey2 recruitment to the IL-6 promoter (-400 ~ -200 bp). These findings suggest that miR-146a and Hey2 form a mutual negative feedback regulatory loop, demonstrating a novel mechanism that regulates inflammatory responses in CAP. Show less

The aim of the present study is to investigate the role of RNA interference in the inhibition of MUC1 gene expression in occurrence and metastasis of oral squamous cell carcinoma (OSCC) and its in-depth mechanisms. The OSCC and normal oral mucosa tissues, as well as normal oral epithelial cell line HOK and OSCC cell line SCC-4, Cal-27, TSCCA, Tca8113 were obtained to detect the expression of MUC1. Slug expression in OSCC and normal oral mucosa tissues was also determined. The OSCC cells were grouped to investigate the role of MUC1 gene silencing on proliferation, DNA replication, cell cycle distribution, apoptosis, colony formation ability, epithelial-mesenchymal transition (EMT), invasion, and migration of OSCC cells. We first found higher positive rate of MUC1 and Slug expression in OSCC tissues. Next, it was determined that higher expression of MUC1 was found in OSCC tissues and cells. Furthermore, silencing of MUC1 declined Slug expression, inhibited the proliferation, DNA replication, cell cycle progression, and EMT while inducing apoptosis of OSCC cells. Our study suggests that overexpression of MUC1 is found in OSCC, and MUC1 gene silencing could inhibit the proliferation, invasion, and migration while inducing apoptosis of OSCC cells. Show less