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ObjectivesThis study evaluated Biodentine (BD) after modification with 2 wt% fluorinated graphene (FG).MethodsFG was prepared using the modified Hummers’ method, where sulfuric and phosphoric acids were added to fluorinated graphite and potassium permanganate. The mixture was heated, sifted, filtered, and centrifuged to obtain FG powder. Characterization was performed using XRD, FTIR, TEM, and SEM/EDX. PH was evaluated, And Ca And F ion release were assessed by inductively coupled plasma spectroscopy and ion chromatography, at days 1,14, And 28. Cell viability was performed using the MTT Assay on pulp stem cells, while ALP assay was evaluated by a spectrophotometer. Compressive strength was evaluated by a universal testing machine. Statistical analysis was performed on the data (p ≤ 0.05).ResultsGraphene and C-F bonds of FG were confirmed in XRD and FTIR, while nanosheets were detected in TEM. SEM/EDX showed more surface roughness in modified BD-FG. pH And Ca ion release results showed significantly higher values at day 1 for modified BD-FG, with significantly higher cumulative Ca ion release. Cell viability results showed no significant difference between modified And unmodified Biodentine at days 1 And 7; however, modified BD-FG showed significantly lower values at day 3. No significant difference was observed between the two groups in ALP, while the BD-FG group showed significantly higher compressive strength.ConclusionIncorporating 2 wt% FG into BD increases ion release, hydroxyapatite formation, and mechanical properties without compromising cell viability and differentiation.Clinical relevanceThe addition of FG enhanced the bioactivity of Biodentine and improved its strength without showing cytotoxicity, making it a promising approach that needs further study.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12903-025-06947-7.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiac-specific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multi-electrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses. Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patient-derived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Glyoxalase I (GLO1) is the primary enzyme for detoxification of the reactive dicarbonyl methylglyoxal (MG). Loss of GLO1 promotes accumulation of MG resulting in a recapitulation of diabetic phenotypes. We previously demonstrated attenuated GLO1 protein in skeletal muscle from individuals with type 2 diabetes (T2D). However, whether GLO1 attenuation occurs prior to T2D and the mechanisms regulating GLO1 abundance in skeletal muscle are unknown. GLO1 expression and activity were determined in skeletal muscle tissue biopsies from 15 lean healthy individuals (LH, BMI: 22.4 ± 0.7) and 5 individuals with obesity (OB, BMI: 32.4 ± 1.3). GLO1 protein was attenuated by 26 ± 0.3 % in OB compared to LH skeletal muscle (p = 0.019). Similar reductions for GLO1 activity were observed (p = 0.102). NRF2 and Keap1 expression were equivocal between groups despite a 2-fold elevation in GLO1 transcripts in OB skeletal muscle (p = 0.008). GLO1 knock-down (KD) in human immortalized myotubes promoted downregulation of muscle contraction and organization proteins indicating the importance of GLO1 expression for skeletal muscle function. SIRT1 KD had no effect on GLO1 protein or activity whereas, SIRT2 KD attenuated GLO1 protein by 28 ± 0.29 % (p < 0.0001) and GLO1 activity by 42 ± 0.12 % (p = 0.0150). KD of NAMPT also resulted in attenuation of GLO1 protein (28 ± 0.069 %, p = 0.003), activity (67 ± 0.09 %, p = 0.011) and transcripts (50 ± 0.13 %, p = 0.049). Neither the provision of the NAD+ precursors NR nor NMN were able to prevent this attenuation in GLO1 protein. However, NR did augment GLO1 specific activity (p = 0.022 vs NAMPT KD). These perturbations did not alter GLO1 acetylation status. SIRT1, SIRT2 and NAMPT protein levels were all equivocal in skeletal muscle tissue biopsies from individuals with obesity and lean individuals. These data implicate NAD+-dependent regulation of GLO1 in skeletal muscle independent of altered GLO1 acetylation and provide rationale for exploring NR supplementation to rescue attenuated GLO1 abundance and activity in conditions such as obesity. Graphical abstractImage 1