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The development and progression of hyperglycemia (HG) and HG-associated atherosclerosis are exacerbated by mitochondrial dysfunction due to dysregulated mitochondria-derived ROS generation. We recently synthesized a novel mitochondria-targeted esculetin (Mito-Esc) and tested its dose-response therapeutic efficacy in mitigating HG-induced atherosclerosis in db/db mice. In comparison to simvastatin and pioglitazone, Mito-Esc administration resulted in a considerable reduction in body weights and improved glucose homeostasis, possibly by reducing hepatic gluconeogenesis, as indicated by a reduction in glycogen content, non-esterified free fatty acids (NEFA) levels, and fructose 1,6-bisphosphatase (FBPase) activity. Interestingly, Mito-Esc treatment, by regulating phospho-IRS and phospho-AKT levels, greatly improved palmitate-induced insulin resistance, resulting in enhanced glucose uptake in adipocytes and HepG2 cells. Also, and importantly, Mito-Esc administration prevented HG-induced atheromatous plaque formation and lipid accumulation in the descending aorta. In addition, Mito-Esc administration inhibited the HG-mediated increase in VACM, ICAM, and MAC3 levels in the aortic tissue, as well as reduced the serum pro-inflammatory cytokines and markers of senescence. In line with this, Mito-Esc significantly inhibited monocyte adherence to human aortic endothelial cells (HAECs) treated with high glucose and reduced high glucose-induced premature senescence in HAECs by activating the AMPK-SIRT1 pathway. In contrast, Mito-Esc failed to regulate high glucose-induced endothelial cell senescence under AMPK/SIRT1-depleted conditions. Together, the therapeutic efficacy of Mito-Esc in the mitigation of hyperglycemia-induced insulin resistance and the associated atherosclerosis is in part mediated by potentiating the AMPK-SIRT1 axis. KEY MESSAGES: Mito-Esc administration significantly mitigates diabetes-induced atherosclerosis. Mito-Esc improves hyperglycemia (HG)-associated insulin resistance. Mito-Esc inhibits HG-induced vascular senescence and inflammation in the aorta. Mito-Esc-mediated activation of the AMPK-SIRT1 axis regulates HG-induced endothelial cell senescence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: The current study aimed to assess the efficiency of two desensitizing dentifrices on the management of dental hypersensitivity., Materials and Methods: For the purpose of this investigation, 60 extracted human sound premolar teeth that were removed for orthodontic purposes were collected. On the buccal cervical areas, an inverted-cone bur was used to create cavities that were 2 mm deep and 3 mm wide. The blocks were submerged in 17% ethylenediaminetetraacetic acid (EDTA) for 40 minutes in order to ensure the complete dentin tubule opening. Following preparation, all samples were split into three groups, each containing 20 samples, Group A: Control, Group B: Dentifrice containing calcium sodium phosphosilicate, Group C: Dentifrice containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). Scanning electron microscopy (SEM) was used to assess the occlusion of dentinal tubules. One-way analysis of variance (ANOVA) was used to assess the desensitization efficacy of dentifrices. At a p -value less than 0.05, statistical significance was determined., Result: Before application of different dentifrices, the maximum dentinal tubules opened in dentifrice containing CPP-ACP group (4.24 ± 0.10) followed by control group (4.18 ± 0.01) and dentifrice containing calcium sodium phosphosilicate (4.12 ± 0.06). And there was no significant difference between the different dentifrice groups ( p > 0.001). After application of different dentifrices, the highest occlusion of dentinal tubules found in dentifrice containing CPP-ACP group (2.50 ± 0.05) followed by dentifrice containing calcium sodium phosphosilicate (2.84 ± 0.10) and control group (4.02 ± 0.07) and there was a highly significant difference between the different dentifrice groups ( p < 0.001)., Conclusion: On conclusion, dentifrice containing CPP-ACP exhibited the highest level of dentinal tubule occlusion in comparison to the control group and dentifrice containing calcium sodium phosphosilicate., Clinical Significance: Dentinal hypersensitivity (DH) is a condition that is frequently experienced. With variable outcomes, a number of products are utilized in the management of DH. Need is felt in dentistry for a material that chemically reacts, physically occludes and adheres intimately to dentinal tubules to reduce the possibility of its recurrence. How to cite this article: Pulipaka S, Ramanna PK, Samson A, et al. Assessment of the Effectiveness of Desensitizing Dentifrices on Management of Dental Hypersensitivity: An In Vitro Study. J Contemp Dent Pract 2024;25(5):494-497.

Atherosclerosis, in general, is an age-associated cardiovascular disease wherein a progressive decline in mitochondrial function due to aging majorly contributes to the disease development. Mitochondria-derived ROS due to dysregulated endothelial cell function accentuates the progression of atherosclerotic plaque formation. To circumvent this, mitochondrially targeted antioxidants are emerging as potential candidates to combat metabolic abnormalities. Recently, we synthesized an alkyl TPP + tagged esculetin (Mito-Esc), and in the current study, we investigated the therapeutic efficacies of Mito-Esc and metformin, a well-known anti-diabetic drug, in the amelioration of age-associated plaque formation in the aortas of 12 months aged Apoe -/- and 20 months aged C57BL/6 mice, in comparison to young C57BL/6 control mice. Administration of Mito-Esc or metformin significantly reduced age-induced atherosclerotic lesion area, macrophage polarization, vascular inflammation, and senescence. Further, chronic passaging of human aortic endothelial cells (HAEC) with either Mito-Esc or metformin significantly delayed cellular senescence via the activation of the AMPK-SIRT1/SIRT6 axis. Conversely, depletion of either AMPK/SIRT1/SIRT6 caused premature senescence. Consistent with this, Mito-Esc or metformin treatment attenuated NFkB-mediated inflammatory signaling and enhanced ARE-mediated anti-oxidant responses in comparison to late passage control HAECs. Importantly, culturing of HAECs for several passages with either Mito-Esc or metformin significantly improved mitochondrial function. Overall, Mito-Esc and metformin treatments delay age-associated atherosclerosis by regulating vascular senescence via the activation of AMPK-SIRT1/SIRT6 axis., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

DOT1L, a specific H3K79 methyltransferase, has a tumour-promoting role in various cancers, including triple-negative breast cancer (TNBC). However, the molecular mechanism by which the deregulated DOT1L promotes cancer progression is unclear. Herein, we show that a significantly higher basal level of DOTL1 strongly correlates with MTDH, an oncogene, in clinical TNBC patient cohorts and mediates TNBC progression by enhancing MTDH-induced angiogenesis. In parallel, severe combined immunodeficiency mice-bearing MDA-MB-231 cells with MTDH-Wt or MTDHΔ7 (spliced isoform of MTDH) overexpression constructs showed enhanced blood vessel formations at the tumour site in comparison with control groups. Selective inhibition of DOT1L by EPZ004777, a specific DOT1L inhibitor, or siDOT1L, significantly impaired MTDH-induced proliferation, invasion and angiogenic markers expression in TNBC cells. ChIP assay revealed that Dot1L promotes MTDH-Wt/Δ7 transcription by increasing H3K79me3 levels on its promoter. Dot1L depletion reversed this effect. Mechanistically, DOT1L-induced MTDH caused enhanced nuclear factor kappa B (NF-κB) occupancy on the hypoxia-inducible factor1α (HIF1α) promoter and increased its transcription, leading to elevated levels of proangiogenic mediators in TNBC cells. Moreover, the condition media obtained from MDA-MB-231 cells stably expressing either MTDH-Wt or MTDHΔ7 treated with EPZ004777 or Bay-11-7082 (NF-κB inhibitor) or FM19G11 (HIF1α inhibitor) significantly inhibited MTDH-induced tube formation in human umbilical vein endothelial cells, rat aortic ring sprouting and vessel formations by chick chorioallantoic membrane assay mimicking physiological angiogenic vasculature. Collectively, our findings reveal a novel epigenetic regulation of MTDH by DOTL1, which drives angiogenesis, and that the therapeutic disruption of the DOT1L-MTDH-NF-κB-HIF1α axis may have usefulness in the management of TNBC., (© 2022 Federation of European Biochemical Societies.)

This work is primarily focused on indium sulfide (β-In 2 S 3 ) and cobalt (Co)-doped β-In 2 S 3 nanoflakes as photoanodes for water oxidation. The incorporation of cobalt introduces new dopant energy levels increasing visible light absorption and leading to improved photo-activity. In addition, cobalt ion centers in β-In 2 S 3 act as potential catalytic sites to promote electro-activity. 5 mol% Co-doped β-In 2 S 3 nanoflakes when tested for photoelectrochemical water splitting exhibited a photocurrent density of 0.69 mA cm -2 at 1.23 V, much higher than that of pure β-In 2 S 3 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)