Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells.

BACKGROUND: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu. METHODS: We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors. RESULTS: The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2. CONCLUSION: We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.

Accelerating wound healing: Unveiling synergistic effects of P25/SWCNT/Ag and P25/rGO/Ag nanocomposites within PRP-gelatin scaffold, highlighting the synergistic antimicrobial activity.

Wound healing is a multifaceted biological process requiring innovative strategies to enhance efficiency and counter infections. In this groundbreaking study, we investigate the regenerative potential of platelet-rich plasma (PRP) integrated into a gelatin (GLT) scaffold along with nanocomposites of titanium dioxide (TiO2) (P25)/single-walled carbon nanotubes (SWCNTs)/Ag and P25/reduced graphene oxide (rGO)/Ag. Incorporating these advanced materials into the PRP/GLT delivery system aims to optimize the controlled release of growth factors (GFs) and leverage the exceptional properties of nanomaterials for enhanced tissue repair and wound healing outcomes. Antioxidant activity assessment using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity reveals the superior performance of P25/SWCNTs/Ag compared to P25/rGO/Ag. Their synergistic effects are evaluated in conjunction with antibacterial and antifungal antibiotics. Furthermore, the wound healing potential of P25/SWCNTs/Ag and P25/rGO/Ag, combined with PRP/GLT, is examined. Notably, both nanocomposites exhibit promising synergistic effects with gentamicin and fluconazole against pathogenic strains. Significantly, the inclusion of non-activated PRP substantially augments the wound healing efficacy of P25/SWCNTs/Ag on days 3 (p < 0.01) and 15 (p < 0.05). These findings pave the way for advanced wound dressing and therapeutic interventions, capitalizing on the synergistic effects of PRP and nanomaterials, thus ultimately benefiting patients and advancing regenerative medicine.

Ternary nanocomposite potentiates the lysophosphatidic acid effect on human osteoblast (MG63) maturation.

Aim: This study aimed to investigate the potential of ternary nanocomposite (TNC) to support MG63 osteoblast maturation to EB1089-(3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP) cotreatment. Materials & methods: Binary (P25/reduced graphene oxide [rGO]) nanocomposite was prepared, and silver (Ag) nanoparticles were loaded onto the surface to form TNC (P25/rGO/Ag). The influence of TNC on proliferation, alkaline phosphatase activity and osteogenic gene expression was evaluated in a model of osteoblast maturation wherein MG63 were costimulated with EB1089 and FHBP. Results: TNC had no cytotoxic effect on MG63. The addition of TNC to EB1089-FHBP cotreatment enhanced the maturation of MG63, as supported by the greater alkaline phosphatase activity and OPN and OCN gene expression. Conclusion: TNC could serve as a promising carrier for FHBP, opening up possibilities for its application in bone regeneration.

Nanoparticles (NPs) are often used in medicine because they have certain benefits over traditional drugs, such as increased delivery. Multiple NPs can be combined into hybrid NPs called nanocomplexes, which can have many positive effects. One application of nanomedicine is to encourage the repair of certain body tissues such as bones. Encouraging stem cells to differentiate into bone cells and immature bone cells to mature is key in this process. This study made a ternary nanocomplex (TNC), meaning it was comprised of three NPs. This TNC was designed to deliver a drug called (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), which has been shown to encourage the maturation and development of osteoblasts, a type of bone cell. The TNC was made up of silver NPs, which can kill bacteria; reduced graphene oxide, which enhances the production of bone cells; and titanium dioxide, which has shown effectiveness in wound healing and mixed results in bone tissue regeneration. This TNC was tested on a cell line that comes from a type of bone cancer called MG63. The TNC was found to not be toxic to these cells. TNC incorporation into FHBP treatment enhanced the maturation of MG63. This suggests that these TNCs could be an effective treatment to encourage bone repair following joint replacement surgeries.

Subacute silica nanoparticle exposure induced oxidative stress and inflammation in rat hippocampus combined with disruption of cholinergic system and behavioral functions.

Increasing environmental exposure to silica nanoparticles (SiNPs) and limited neurotoxicity studies pose a challenge for safety evaluation and management of these materials. This study aimed to explore the adverse effects and underlying mechanisms of subacute exposure to SiNPs by the intraperitoneal route on hippocampus function in rats. Data showed that SiNPs induced a significant increase in oxidative/nitrosative stress markers including reactive oxygen species (ROS), malondialdehyde (MDA), protein oxidation (PCO) and nitrite (NO) production accompanied by reduced antioxidant enzyme activity (catalase, superoxide dismutase, and glutathione peroxidase) and decreased glutathione (GSH). Phenotypically, SiNPs exhibited spatial learning and memory impairment in the Morris water maze (MWM) test, a decrease of the discrimination index in the novel object recognition test (NORT) and higher anxiety-like behavior. SiNPs affected the cholinergic system as reflected by reduced acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. In addition, SiNPs significantly increased mRNA expression level of genes related to inflammation (TNF-α, IL-1ß, IL-6, and COX-2) and decreased mRNA expression level of genes related to cholinergic system including choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), AChE, muscarinic acetylcholine receptor M1 (m1AChR) and nicotinic acetylcholine receptors (nAChR). Histopathological results further showed an alteration in the hippocampus of treated animals associated with marked vacuolation in different hippocampus areas. These findings provide new insights into the molecular mechanism of SiNPs-induced hippocampal alterations leading to impairment of cognitive and behavioral functions, and implicating oxidative stress and inflammation in the hippocampus, as well as disruption of cholinergic system.