ABSTRACT Porphyromonas gingivalis ( P. gingivalis ) is a keystone pathogen in periodontal dysbiosis and has been linked to multiple systemic diseases. Ferroptosis is a form of regulated cell death driven by iron‐dependent lipid peroxidation, and accumulating evidence implicates it in P. gingivalis ‐associated tissue injury. This review examines the mechanisms and disease contexts linking P. gingivalis to ferroptosis across experimental models. In inflammatory and tissue‐injury models, P. gingivalis exposure is associated with disrupted iron homeostasis, increased lipid peroxidation, and impaired antioxidant defenses. In contrast, tumor models show reduced ferroptotic sensitivity associated with P. gingivalis . These findings support a context‐dependent model in which P. gingivalis may alter host‐cell susceptibility to ferroptosis through direct bacterial effects and indirect changes in the microbial, inflammatory, and redox environment. This framework highlights how bacterial exposure, host‐cell state, and the disease microenvironment shape ferroptotic responses and provides a basis for evaluating the mechanistic and translational significance of ferroptosis in P. gingivalis ‐associated diseases.
ABSTRACT Tumor invasion implies aberrantly increased cell motility, and is the first step of the cascade of events culminating in the development of distant metastases. The emergence of migratory capacity in epithelial carcinomas, consisting essentially of stationary cells, is linked to the activation of the epithelial‐to‐mesenchymal transition (EMT) program that can range from partial to complete. According to the EMT model, carcinoma cells would weaken cell–cell junctions and extend basal pseudopodia into the interstitium to form adhesive contacts with the extracellular matrix there; eventually, the cytoskeleton would contract, causing the cell to move into the subjacent interstitium and, hence, initiate the actual invasion of the stroma. The so‐called mesenchymal migration implies the appearance of protrusions at the cell front and contractile activity in the cell body and rear, effectively pulling the cell forward. The small GTPases of the Rho family play a crucial role in EMT and cell migration/invasion. The activity of Rac results in the development of a peripheral actin network that exerts a pushing force against the cell membrane at the cell front, leading to the formation of cytoplasmic extensions that establish adhesions with the matrix. Eventually, forward movement of the cell body is produced by Rho‐mediated actomyosin contractility that generates traction force on the substrate. A second single cell migration strategy is called ameboid, and relies on strong contractility of the cytoskeleton generating high cytoplasmic pressure and, therefore, forward propulsion of the cell. A third mode of invasion is collective migration, whereby translocation of tumor cell clusters occurs thanks to partial EMT‐converted leader cells at the front that guide the group of follower cells behind. Indeed, while single cell‐based mesenchymal and ameboid invasion depend on complete EMT, collective invasion relies on partial EMT. However, depending on microenvironmental contexts, tumor cells can plastically switch from one of these modes to another.
ABSTRACT Granulocyte colony‐stimulating factor (G‐CSF) is widely used for stem cell mobilization but is associated with side effects such as pain, which often discourages healthy donors. Jing Si Herbal Tea (JSHT), a novel Chinese herbal formula comprising eight different Chinese herbal medicines, has been shown to exert pleiotropic effects against several disorders. The present study primarily explored the potential effects of JSHT aqueous extract on G‐CSF‐induced stem cell mobilization and the alleviation of G‐CSF‐induced pain. The effects of JSHT on G‐CSF‐induced hematopoietic stem and progenitor cell (HSPC) mobilization and pain‐related responses in mice were comprehensively evaluated using flow cytometric analysis, nociceptive behavioral assessments, and immunofluorescence staining. Animal studies demonstrated that JSHT had no significant effect on white blood cell (WBC) levels or HSPC mobilization. However, it helped replenish the HSPC level in the bone marrow following G‐CSF‐induced mobilization of these cells into the peripheral circulation. Furthermore, JSHT increased IFNγ expression in CD45 + and CD45 + CD34 + cells, suggesting its potential to enhance HSPC activity. JSHT also alleviated thermal hyperalgesia, with effects comparable to those of acetaminophen (APAP), by reducing neuroinflammation and modulating the expression of cannabinoid receptor 1 (CB1) and the sodium channel Nav1.8 in the dorsal root ganglia (DRG), thereby reducing G‐CSF‐induced pain. JSHT had no effect on HSPC mobilization into the peripheral blood but might help regulate HSPC level within the bone marrow and potentially enhance HSPC function during G‐CSF treatment. Additionally, JSHT effectively attenuated G‐CSF‐induced pain, suggesting its potential as a supportive therapy during G‐CSF‐induced stem cell mobilization.
