We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well‐known reactive oxidative species‐ (ROS‐) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis‐like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome‐associated LC3‐II protein, degradation of p62, and increased expression of beclin‐1. While both MD and AA+MD increased phosphorylation of AMP‐activated protein kinase (AMPK), the well‐known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51‐like kinase 1 (ULK1), and increased the expression of several autophagy‐related genes. Antioxidant N‐acetyl cysteine reduced both MD‐ and AA+MD‐induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD‐induced AMPK‐dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.

The calcium silicate-based sealers currently available on the market have different compositions and formulations, which is why their physical and chemical properties may vary. (1) The aim of the study was to measure the physico-chemical properties of calcium silicate-based sealers and their push-out bond strength to root dentine, comparing two push-out testing protocols. (2) Standardized specimens of EndoSequence BC, BioRoot RCS, MTA Fillapex, and AH Plus (control) were subjected to pH measurements over 28 days. Radiopacity was measured using a CCD sensor, and flexural strength was assessed using a three-point bending setup. Push-out bond strength was measured in coronal, middle, and apical sections of 40 single-root teeth (conventional method), and cylindrical cavities were prepared for all sealers on the same root dentine disks in 11 third molars (disk method). (3) EndoSequence BC exhibited a higher pH than MTA Fillapex and the highest radiopacity (p < 0.05). The highest flexural and push-out bond strengths were found for AH Plus. The push-out bond strength of EndoSequence BC and BioRoot RCS was higher than MTA Fillapex (p < 0.05). The conventional and disk methods exhibited similar push-out bond strength results, but the data were more homogeneously distributed in the disk method. (4) All calcium silicate-based sealers exhibited a higher pH than AH Plus. MTA Fillapex did not meet the ISO standard. Calcium silicate-based sealers showed weaker performance in terms of physical properties compared to AH Plus.

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.

Second-generation (atypical) antipsychotics are central to the treatment of schizophrenia and related disorders but are frequently associated with significant metabolic adverse effects, particularly weight gain and obesity. These complications can impair treatment adherence and substantially increase the risk of cardiovascular and metabolic comorbidities. Accumulating evidence indicates that antipsychotic-induced metabolic dysregulation arises from complex interactions between central neurotransmitter systems and neuroendocrine regulators of appetite and energy balance. Among these, the orexigenic peptide ghrelin and its receptor, growth hormone secretagogue receptor 1a(GHSR1a), play a key role in linking peripheral metabolic signals with central reward pathways that govern feeding behavior. Ghrelin signaling also functionally interacts with multiple neurotransmitter systems and the hypothalamic-pituitary-adrenal (HPA) axis, all of which are targets of atypical antipsychotics. This narrative review examines the convergence of ghrelin signaling with serotonergic, dopaminergic, histaminergic, and cholinergic pathways involved in appetite regulation. We further consider how sex-dependent differences in ghrelin signaling, antipsychotic pharmacokinetics, and bidirectional interactions with the HPA axis contribute to metabolic vulnerability. In addition, we explore how the pharmacodynamic profiles of second-generation antipsychotics influence these neurochemical and neuroendocrine networks, highlighting shared receptor-level mechanisms that may promote increased food intake and metabolic dysfunction. Integrating insights from neuropharmacology, neuroendocrinology, and psychiatric neuroscience, this review outlines mechanisms underlying antipsychotic-associated obesity and identifies potential targets to mitigate metabolic side effects while preserving therapeutic efficacy.

The wettability is the tendency of a liquid to disperse or adhere to a solid surface. The aim of research was to evaluate and compare the wettability of newly synthesized calcium aluminate-based dental cement and mineral trioxide aggregate (MTA). Two materials were examined: novel calcium aluminate cement with added zirconium dioxide (CaAl+ZrO2) and MTA (Cerkamed, Poland). The wettability of disc-shaped samples, produced by mixing and moulding of cement, was calculated through the contact angle between the disc and a drop of the reference liquid (glycerol, diiodomethane), using the ImageJ computer software. No significant difference in wettability was noted between CaAl+ZrO2 and MTA when glycerol was applied. CaAl+ZrO2 expressed significantly higher contact angle values compared to MTA (p<0.05) when diiodomethane was used. Both tested materials possess similar wettability properties when introduced to glycerol. MTA showed better wettability after the placement of diiodomethane.

The novel dental material, calcium aluminate with zirconium dioxide (CaAl+ZrO2) has good physical properties, but its biological effects need to be elucidated. This study aimed to investigate the effects of implanted CaAl+ZrO2 on rat brain tissue. 24 adult male Wistar rats were implanted intraalveolarly with CaAl+ZrO2 or control material mineral trioxide aggregate (MTA). The rats were weighed before implantation and before euthanasia. Cage-side observation for neurotoxicity signs was conducted. Animals were sacrificed after 30 and 180 days. Histological specimens of hippocampus revealed that perinuclear vacuolization and neuronal necrosis decreased over time, in both CaAl+ZrO2 and MTA. 180 days postimplantation, the percentage of necrotic cells and neurons with perinuclear vacuolization was significantly lower in CaAl+ZrO2 than in MTA group. Intraalveolar implantation of CaAl+ZrO2 did not induce neurotoxicity signs and significant changes in hippocampal morphology in rats. These results, together with its physicochemical properties, indicate that CaAl+ZrO2 possesses good biological properties and could be applied in the clinical studies/dentistry.