Pulsed electromagnetic fields synergize with graphene to enhance dental pulp stem cell-derived neurogenesis by selectively targeting TRPC1 channels.

Conventional root canal treatment replaces the infected pulp with defined materials. Alternative cell-based tissue engineering strategies aim to regenerate a fully functional pulp within the root canal. Despite recent advances in this area, however, the regeneration of an innervated pulp remains a major challenge in the field. Both graphene (2DG) and pulsed electromagnetic fields (PEMFs) independently have been shown to promote diverse cellular developmental programs. The present study showed that 2DG promoted the neurogenic induction of human dental pulp stem cells (hDPSCs) by upregulating and accelerating the expression of mature neuronal markers. Notably, 2DG induced the highest expression of transient receptor potential canonical cation channel type 1 (TRPC1) during early neurogenesis. As brief PEMF exposure promotes in vitro differentiation by activating a TRPC1-mitochondrial axis, an opportunity to combine 2DG with developmentally targeted PEMF exposure for synergistic effects was realizable. Neurogenic gene expression, neurotransmitter release, and reactive oxygen species (ROS) production were greatly enhanced by a brief (10 min) and low amplitude (2 mT) PEMF exposure timed to coincide with the highest TRPC1 expression from hDPSCs on 2DG. In contrast, hDPSCs on glass were less responsive to PEMF exposure. The capacity of PEMFs to promote neurogenesis was precluded by the administration of penicillin/streptomycin, mirroring previous studies demonstrating that aminoglycoside antibiotics block TRPC1-mediated calcium entry and verifying the contribution of TRPC1 in this form of magnetoreception. Hence, graphene created a more conducive environment for subsequent PEMF-stimulated neurogenic induction of hDPSCs through their mutual capacity to activate TRPC1with subsequent ROS production.

Motor and behavioral changes in mice with cisplatin-induced acute renal failure.

We have previously shown that chronic renal failure in rats induces changes in motor activity and behavior. Similar work on the possible effects of acute renal failure (ARF) induced by cisplatin (CP) is lacking. This is the subject matter of the current work. CP was injected intraperitoneally (i.p.) at a single dose of 20 mg/kg to induce a state of ARF, and three days later, its effects on motor activity, thermal and chemical nociceptive tests, neuromuscular coordination, pentobarbitone-sleeping time, exploration activity and two depression models were investigated. The platinum concentration in the kidneys and brains of mice was also measured. The occurrence of CP-induced ARF was ascertained by standard physiological, biochemical and histo-pathological methods. CP induced all the classical biochemical, physiological and histopathological signs of ARF. The average renal platinum concentration of CP-treated mice was 5.16 ppm, but there was no measurable concentration of platinum in the whole brains. CP treatment significantly decreased motor and exploration activities, and increased immobility time in depression models, suggesting a possible depression-like state. There was also a significant decrease in neuromuscular coordination in CP-treated mice. CP, given at a nephrotoxic dose, induced several adverse motor and behavioral alterations in mice. Further behavioral tests and molecular and biochemical investigations in the brains of mice with CP-induced ARF are warranted.

Some physiological and histological aspects of the gastrointestinal tract in a mouse model of chronic renal failure.

INTRODUCTION: It has been reported that mice with 5/6 nephrectomy- induced chronic renal failure (CRF) have reduced gastrointestinal transit (GIT) and increased fecal moisture content (FMC). We have recently shown that feeding adenine (0.2%, w/w) to mice can be used as a model of CRF. Here, we investigated the possible effects of adenine-induced CRF on several in vivo and in vitro aspects of GIT physiology and histology of the stomach, duodenum, ileum and colon in mice. METHODS: The effects of CRF induced by feeding adenine (0.2%, w/w for 2 or 4 weeks) on the gastric emptying index (GEI), GIT, FMC and bead expulsion test (BET) were investigated. GIT was measured by the charcoal meal test and GEI by the difference between full and empty stomach weights. Fresh and dried feces were weighed to calculate the FMC. Renal function was assessed histologically, and biochemically in plasma and urine. The light microscopic histology of the different parts of the gut, as well as the in vitro contractility of the isolated ileum was also assessed. RESULTS: Feeding adenine for 2 or 4 weeks resulted in CRF. The BET was significantly increased in mice given adenine for 2 but not 4 weeks, while the GEI was significantly increased in mice treated with adenine for 4 but not 2 weeks. No significant differences between control and adenine-treated mice were found in GIT, FMC or the histology of the different parts of the gut. Acetylcholine-induced contractions of the ileum of adenine-treated rats were not significantly different from those of the controls. DISCUSSION: Feeding adenine for either 2 or 4 weeks resulted in CRF, but it would appear that this model produces effects on the gastrointestinal tract that are milder than those reported before in animal models with 5/6 nephrectomy-induced-CRF.