Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg²⁺-crosslinked methacrylate gelatin as the "shell" and Zn²⁺-loaded poly (lactic-co-glycolic acid) (PLGA) as the "core" was designed. The chimeric microspheres allow continuous delivery of Mg²⁺ or Zn²⁺ at the exact required phase in SCI pathological process. Early release of Mg²⁺ reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn²⁺ at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.

2025-05-01·European Journal of Pharmacology

Zinc treatment prevents IgE-mediated Ca2+ influx and allergic response in RBL-2H3 cells

Article

作者: Sato, Kaho ; Otsuka, Tomohiro ; Tanaka, Hiroyuki ; Hara, Hirokazu ; Kamiya, Tetsuro

Zinc (Zn) is an essential metal in the body. It binds to many proteins and regulates their functions. In the immune system, it is known that administration of ZnSO₄ suppresses T cell activation, but its effects on allergies are still unknown. In this study, we investigated the effects of ZnSO₄ administration on allergic reactions using the rat basophilic leukemia cell line, RBL-2H3. ZnSO₄ treatment inhibited cell degranulation induced by antigen and IgE stimulation, as well as by A23187, a Ca²⁺ ionophore. Antigen and IgE stimulation increased mRNA expression of IL-4, IL-13, and COX-2, and ZnSO₄ treatment inhibited this expression. The elevation of intracellular Zn concentration and depletion of Zn did not affect degranulation. Phosphorylation of the proteins spleen tyrosine kinase, p38, ERK1/2, JNK, and Akt was increased by antigen stimulation, but ZnSO₄ treatment did not inhibit this phosphorylation. ZnSO₄ treatment inhibited the elevation of intracellular Ca²⁺ concentration induced by antigen and IgE stimulation, as well as by A23187. Additionally, ZnSO₄ treatment inhibited thapsigargin, a store-operated Ca²⁺ entry stimulant, from inducing degranulation and increasing intracellular Ca²⁺ concentration. These data indicate that exogenous Zn²⁺ possesses a preventive effect on RBL-2H3 activation via inhibition of Ca²⁺ influx. The effect of Zn may involve Ca²⁺ release-activated channels. This study suggests that ZnSO₄ treatment is valuable in suppressing allergic responses.

2025-03-01·Carbohydrate Polymers

Combining antibacterial and wound healing features: Xanthan gum/guar gum 3D-printed scaffold tuned with hydroxypropyl-β-cyclodextrin/thymol and Zn2+

Article

作者: Concheiro, Angel ; Diaz-Rodriguez, Patricia ; Virzì, Nicola Filippo ; Otero, Ana ; Pittalà, Valeria ; Mazzaglia, Antonino ; Alvarez-Lorenzo, Carmen

Biofilm formation on biological and material surfaces represents a heavy health and economic burden for both patient and society. To contrast this phenomenon, medical devices combining antibacterial and pro-wound healing abilities are a promising strategy. In the present work, Xanthan gum/Guar gum (XG/GG)-based scaffolds were tuned with thymol and Zn²⁺ to obtain wound dressings that combine antibacterial and antibiofilm properties and favour the healing process. The tuning process preserved the 3D extrusion-based printability of the XG/GG ink. Scaffolds swelling profile was assessed in PBS pH 7.4, and the resistance to compressive forces was studied using a texturometer. The scaffolds microarchitectures were analyzed by SEM, while ATR-FTIR spotlighted the chemical modifications of the customized materials. Thymol and Zn²⁺ release was analyzed in biologically relevant media, showing a burst release in the first hours. The antibacterial properties were confirmed against S. aureus, P. aeruginosa, and S. epidermidis by isothermal microcalorimetry and biofilm viable cell counting. Incorporation of hydroxypropyl-β-cyclodextrin (HPβCD) improved thymol loading (7- and 14-times higher thymol content) and enhanced the antimicrobial and antioxidant performances of the dressing, while the presence of Zn²⁺ strongly potentiated the antimicrobial activity, showing a potent antibiofilm response in both Gram-positive and Gram-negative strains of clinical concern. The thymol and Zn²⁺ combination led to a reduction of 99.95 %, 99.99 %, and 98.26 %, of biofilm formation against S. aureus, P. aeruginosa, and S. epidermidis, respectively. Furthermore, the scaffolds demonstrated good hemocompatibility, cytocompatibility, tissue integration and pro-angiogenic features in an in ovo CAM model.

100 项与 Zn-2 相关的药物交易

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