Enterococcus faecalis (E. faecalis) is commonly associated with persistent periapical infections. Even after multiple courses of root canal therapy, the infection is difficult to eradicate due to its drug resistance and adaptability. However, root canal treatment will remove nutrients from the root canal and make the remaining E. faecalis near starvation. Iron is an essential element for the growth and metabolism of E. faecalis, but previous studies were mostly based on bacterial nutrient sufficient conditions. Therefore, in this study, the starvation state was used as the breakthrough point to explore the mechanism of iron on the biofilm formation of E. faecalis, so as to be more suitable for clinical practice. In this study, we first constructed a starving E. faecalis model. Subsequently, we found that iron supply promoted biofilm formation in starved E. faecalis, with more eDNA in the biofilm. Iron starvation induced by the iron competitive inhibitor gallium nitrate reduced biofilm formation but increased the proportion of eDNA. In contrast, high iron levels in the environment counteracted this inhibition of biofilm formation. Following DNase I treatment, both the eDNA content and viable bacteria within the biofilm of the iron-supply group exhibited a statistically significant reduction. These results suggest that iron supply may regulate the proliferation of active bacteria by regulating eDNA release, thereby promoting biofilm formation of starved E. faecalis and providing a new perspective on its survival strategy under stress.
Tao Liu,Wenlong Liu,Mingkang Zhang,Wuyang Yu,Fan Gao,Chuxin Li,Shi-Bo Wang,Jun Feng,Xian-Zheng Zhang
Non-apoptotic ferroptosis is of clinical importance because it offers a solution to the inevitable biocarriers of traditional apoptotic therapeutic means. Inspired by industrial electro-Fenton technology featured with electrochemical iron cycling, we construct ferrous-supply-regeneration nanoengineering to intervene tumorous iron metabolism for enhanced ferroptosis. Fe3+ ion and naturally derived tannic acid (TA) spontaneously form a network-like corona onto sorafenib (SRF) nanocores. The formed SRF@FeIIITA nanoparticles can respond to a lysosomal acid environment with corona dissociation, permitting SRF release to inhibit GPX4 enzyme for ferroptosis initiation. TA is arranged to chemically reduce the liberated and the ferroptosis-generated Fe3+ to Fe2+, offering iron redox cycling to, thus, effectively produce lipid peroxide required in ferroptosis. Sustained Fe2+ supply leads to long-term cytotoxicity, which is identified to be specific to H2O2-overloaded cancer cells but minimal in normal cells. SRF@FeIIITA-mediated cell death proves to follow the ferroptosis pathway and strongly inhibits tumor proliferation. Moreover, SRF@FeIIITA provides a powerful platform capable of versatile integration between apoptosis and non-apoptosis means. Typically, photosensitizer-adsorbed SRF@FeIIITA demonstrates rapid tumor imaging owing to the acid-responsive fluorescence recovery. Together with ferroptosis, imaging-guided photodynamic therapy induces complete tumor elimination. This study offers ideas about how to advance anticancer ferroptosis through rational material design.
Jia Chen,Yu Xia,Qian Lan,Min Hu,Yueying Xu,Quanxin Wu,Xinguang Liu,Yun Liu
Uncontrolled hemorrhage is a main cause of pre-hospital death. Given the importance of hemostatic wound dressings in pre-hospital emergency treatment, novel composite materials are required for fast hemostasis, synergistic bacterial ablation with negligible resistance and wound healing acceleration. Herein, multifunctional SCTF cryogels were fabricated by the simultaneous cross-linking of sodium alginate (SA) and tannic acid (TA) with Fe 3+ ions. As a result, the prepared SCTF cryogels consisted of Fe 3+ /TA-based metal phenolic networks (MPNs) and Fe 3+ /SA-based 3D skeleton for collagen (CA). MPNs endowed the cryogels with photothermal effect, photothermal-enhanced Fenton activity and pH/photothermal dual-responsive release property of TA and Fe 2+ , which were beneficial for the antibacterial capacity. Due to the intrinsic high porosity, in vitro and in vivo assays demonstrated that SCTF cryogels possessed good hemostatic capacity. Moreover, the synergistic photothermal therapy (PTT), chemodynamic therapy (CDT) and pH/photothermal responsive chemo-therapy dramatically enhanced the bactericidal efficacy of SCTF cryogels both in vitro and in vivo . Eventually, their outstanding healing-accelerating effects were confirmed via animal experiments, which were attributed to the presence of CA and TA. Therefore, the developed composite materials could offer new strategy on exploiting multifunctional wound dressing for clinical applications in the future.
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