Background: Intervertebral disc degeneration (IVDD) is a prevalent degenerative disease, with low back pain as its primary clinical symptom, imposing significant burdens on individuals and society. With the aging population, IVDD is becoming an inevitable challenge. Current research indicates that the pathogenesis of IVDD is primarily driven by aging, mechanical stress, cell death, and genetics, leading to the loss of nucleus pulposus and degradation of the extracellular matrix within the intervertebral disc.Objective: This review aims to explore the relationship between the mechanisms of ferroptosis and cuproptosis, two newly discovered modes of cell death, and their potential as therapeutic targets for IVDD.Methods: We conducted a comprehensive review of recent studies on ferroptosis and cuproptosis in IVDD, analyzing the mechanisms of these cell death patterns and their potential role in IVDD progression.Results: Ferroptosis and cuproptosis have been found to be closely related to IVDD. These cell death modes are implicated in the pathological processes of IVDD, suggesting a potential link between their mechanisms and the disease's progression.Conclusion: The mechanisms of ferroptosis and cuproptosis are closely related to IVDD, and these pathways may be potential targets for IVDD treatment, providing new directions for clinical treatment of IVDD and future research.

Endothelial cells (ECs) of endothelial-to-mesenchymal transition (EndMT) are drivers of cardiac fibrosis. BRD4 has recently been identified as an epigeneti

Kaixuan Qibi granules (KXGs) have exhibited favorable therapeutic outcomes in addressing a wide range of ailments. They have established their efficacy as a traditional Chinese medicine formulation, particularly for cardiovascular and cerebrovascular diseases associated with myocardial fibrosis (MF). Targeting of bromodomain-containing protein 4 (BRD4) represents an efficacious strategy for addressing inflammation (a pivotal factor in MF progression). However, revealing the inhibitory impact of KXGs on BRD4 in MF development is elusive. We investigated the impact of KXGs on MF and elucidated the regulatory mechanism of BRD4 in MF by KXGs in vitro and in vivo. Induction of an in vivo model of MF was achieved in C57BL/6 mice by intraperitoneal administration of isoproterenol (ISO) over 21 days. After administering different doses of KXGs and fosinopril (FOS) via oral gavage for 21 days, metabolite levels, myofibril accumulation, and collagen deposition were assessed using standardized assays. To simulate an inflammatory reaction in vitro, mouse monocyte–macrophage leukemia (RAW264.7) cells were stimulated with lipopolysaccharide (LPS). The intervention effect of KXGs on BRD4 and the nuclear factor-kappa B/NOD-like receptor protein 3 (NF-κB/NLRP3) pathway was evaluated using western blotting and immunofluorescence methods. In this study, we observed a notable reduction in the extent of fibrotic tissue accompanied by organized collagen following treatment with KXGs. KXGs exhibited a significant regulatory effect on metabolite levels while also inhibiting BRD4-related pathways and the inflammatory response. Later, KXGs exhibited downregulation the expression of BRD4, phosphorylated (p)-NF-κB p65 (phosphor/total), NLRP3, ASC, caspase-1, and interleukin-1β (IL-1β) in both in vitro and in vivo models of MF development. KXGs attenuated MF progression by modulating the NF-κB/NLRP3 signaling pathway through inhibition of BRD4 activity.