The theranostic agent iron–quercetin complex (IronQ) provides a T1-positive magnetic resonance imaging (MRI) contrast agent. The magnetically IronQ-labeled cells can be used for cell tracking and have active biological applications in promoting cell and tissue regeneration. However, a detailed investigation of IronQ’s cytotoxicity and genotoxicity is necessary. Thus, this study aimed to evaluate the possibility of IronQ inducing cytotoxicity and genotoxicity in peripheral blood mononuclear cells (PBMCs). We evaluated the vitality of cells, the production of reactive oxygen species (ROS), the level of antioxidant enzymes, and the stability of the genetic material in PBMCs treated with IronQ. The results show that IronQ had a negligible impact on toxicological parameters such as ROS production and lipid peroxidation, indicating that it is not harmful. IronQ-labeled PMBCs experienced an insignificant depletion of antioxidant enzyme levels at the highest concentration of IronQ. There is no evident genotoxicity in the magnetically IronQ-labeled PBMCs. The results show that IronQ does not potentiate the cytotoxicity and genotoxicity effects of the labeled PMBCs and might be safe for therapeutic and cell tracking purposes. These results could provide a reference guideline for the toxicological analysis of IronQ in in vivo studies.

Cell-based therapy is a highly promising treatment paradigm in ischemic disease due to its ability to repair tissue when implanted into a damaged site. These therapeutic effects involve a strong paracrine component resulting from the high levels of bioactive molecules secreted in response to the local microenvironment. Therefore, the secreted therapeutic can be modulated by preconditioning the cells during in vitro culturing. Herein, we investigated the potential use of magnetic resonance imaging (MRI) probes, the “iron–quercetin complex” or IronQ, for preconditioning peripheral blood mononuclear cells (PBMCs) to expand proangiogenic cells and enhance their secreted therapeutic factors. PBMCs obtained from healthy donor blood were cultured in the presence of the iron–quercetin complex. Differentiated preconditioning PBMCs were characterized by immunostaining. An enzyme-linked immunosorbent assay was carried out to describe the secreted cytokines. In vitro migration and tubular formation using human umbilical vein endothelial cells (HUVECs) were completed to investigate the proangiogenic efficacy. IronQ significantly increased mononuclear progenitor cell proliferation and differentiation into spindle-shape-like cells, expressing both hematopoietic and stromal cell markers. The expansion increased the number of colony-forming units (CFU-Hill). The conditioned medium obtained from IronQ-treated PBMCs contained high levels of interleukin 8 (IL-8), IL-10, urokinase-type-plasminogen-activator (uPA), matrix metalloproteinases-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α), as well as augmented migration and capillary network formation of HUVECs and fibroblast cells, in vitro. Our study demonstrated that the IronQ-preconditioning PBMC protocol could enhance the angiogenic and reparative potential of non-mobilized PBMCs. This protocol might be used as an adjunctive strategy to improve the efficacy of cell therapy when using PBMCs for ischemic diseases and chronic wounds. However, in vivo assessment is required for further validation.

To determine the frequency and association of alleles at human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 loci in VKH disease patients from Northern Thailand. A case–control study was conducted with...

Impaired wound healing, particularly in diabetic and chronic wounds, remains a significant global health challenge. While current therapies show promise, their effectiveness is often constrained by high costs, limited accessibility, and inconsistent outcomes across patient populations. This study investigates the potential of the Iron-Quercetin complex (IronQ) to enhance the regenerative secretory profile of peripheral blood mononuclear cells (PBMCs), with the aim of developing a cost-effective, cell-free therapeutic approach. PBMCs isolated from both healthy and diabetic donors were preconditioned with IronQ for 10 days. The resulting secretomes were analyzed for their protein and metabolic profiles, focusing on pro-angiogenic and immunomodulatory factors. In vitro assays were performed to assess the effects of IronQ-preconditioned secretomes on the proliferation, migration, and collagen production of endothelial cells, fibroblasts, and keratinocytes. IronQ preconditioning significantly enriched PBMC secretomes with cytokines such as TGF-α, TNF-α, IL-6, IL-10, HGF, G-CSF, M-CSF, GM-CSF, and GRO-α, along with enhanced glycolytic activity and the production of bioactive metabolites. Furthermore, these secretomes promoted the proliferation and migration of endothelial cells, fibroblasts, and keratinocytes, as well as collagen production by fibroblasts, with consistent effects observed across both healthy and diabetic donors. Collectively, these findings support the potential of IronQ-preconditioned PBMC secretomes as a scalable, autologous, and cost-effective alternative to current cell-based therapies for diabetic wound healing, warranting further in vivo and clinical evaluation.

Triple-negative breast cancer (TNBC) presents a major clinical challenge due to its aggressive behavior, limited targeted therapies, and frequent development of chemoresistance. Resistance to doxorubicin (DOX), a key chemotherapeutic agent, is often associated with epithelial-mesenchymal transition (EMT), overexpression of multidrug resistance (MDR) proteins, and dysregulation of microRNAs (miRNAs). This study investigates the potential of pentagalloyl glucose (PGG), a naturally occurring polyphenol, to overcome DOX resistance in TNBC cells by targeting EMT, miRNA expression, and MDR transporter activity. DOX-resistant MDA-MB-231/ADR cells were established and characterized. The cytotoxic and chemosensitizing effects of PGG were evaluated through MTT assays, apoptosis analysis, migration and invasion assays, Western blotting, miRNA sequencing, qRT-PCR, and drug accumulation studies. PGG significantly restored DOX sensitivity in resistant TNBC cells, as demonstrated by a reduction in the half-maximal inhibitory concentration (IC₅₀) and increased apoptosis. An EMT reversal effect was observed through upregulation of E-cadherin and downregulation of ZEB1 and vimentin, accompanied by reduced cell migration and invasion. miRNA profiling revealed the upregulation of miR-200c-3p and other tumor-suppressive miRNAs. Notably, overexpression of miR-200c-3p alone enhanced chemosensitizing and DOX-induced apoptosis in MDA-MB-231/ADR cells, highlighting its role in drug sensitivity. Additionally, PGG reduced the expression of P-glycoprotein (P-gp) and multidrug resistance protein-1(MRP-1), increased intracellular DOX accumulation, and inhibited efflux activity. In conclusion, PGG reverses DOX resistance in TNBC cells through multiple mechanisms involving EMT inhibition, MDR suppression, and restoration of miR-200c-3p expression. These findings suggest that PGG holds promise as an adjuvant therapeutic agent for managing multidrug-resistant TNBC.