Background: Intervertebral disc degeneration (IVDD), a prevalent spinal disorder, is closely associated with abnormal mechanical stress. The nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP) collectively respond to mechanical loading. The mechanosensitive Piezo 1 ion channel senses mechanical stress changes and converts the mechanical signals into chemical signals, and serves a pivotal role in IVDD pathogenesis. Objective: This review summarizes the regional effects of Piezo 1 on mechanical stress‐induced IVDD and evaluates therapeutic strategies targeting Piezo 1 to maintain disc homeostasis. Methods: A systematic search of preclinical and clinical studies was conducted to delineate Piezo 1's phenotypic impacts, mechanistic pathways, and therapeutic potential in NP, AF, and CEP. Results: In the NP, activated Piezo 1 contributes to cellular senescence, apoptosis, ferroptosis, extracellular matrix (ECM) degradation and synthesis, oxidative stress, inflammation, and catabolic processes. Key regulatory targets involved include NLRP3, MAPK, p38, MMPs, ADAMTS, p65, Periostin, p53, p16, GRP78, CHOP, Cyt‐c, and Drp1. In the CEP, Piezo 1 mediates inflammation‐induced CEP degeneration through the CaMKII/Drp1 pathway and further participates in cellular senescence and apoptosis by activating Bax and caspase‐3 while inhibiting Bcl‐2. In the AF, Piezo 1 mediates apoptosis through the Ca ²⁺ /Calpain2/Caspase‐3 signaling pathway. Therapeutically, targeting Piezo 1 has demonstrated significant preclinical potential, including attenuating pathological alterations via pharmacological inhibition, selectively suppressing degenerative cascades through genetic/RNAi approaches, and modulating channel activity by nutritionally regulating membrane lipids. Conclusion: Piezo 1 serves as a critical mechanotransducer in IVDD, exhibiting region‐specific effects on disc pathophysiology. Targeting Piezo 1 signaling not only offers mechanistic insights but also holds translational potential as a therapeutic strategy to improve IVDD, meriting further exploration in preclinical and clinical contexts.

Cancer threatens the health and lives of people around the world and causes a heavy economic burden on families and society. Dysbiosis of the gut microbiota has been observed in cancer patients and is an important factor in cancer progression. Quercetin, a widely distributed dietary flavonol, exhibits pleiotropic anti-cancer activities in preclinical models. Importantly, recent studies reveal a bidirectional crosstalk between quercetin and the gut microbiota that may critically shape its biological effects. Specifically, gut microbiota enzymes mediate quercetin biotransformation and produce tumor-suppressive quercetin metabolites. On the other hand, quercetin remodels specific gut microbial species and their metabolites to promote anti-tumor activity. This review provides a timely and systematic synthesis of the latest findings regarding quercetin, gut microbiota, and cancer. Furthermore, we discuss strategies to enhance this interaction for improved cancer therapy. By highlighting the pivotal role of the gut microbiota, this review offers novel insights and a refined theoretical framework to guide future research and potential clinical translation of quercetin in cancer prevention and treatment.