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ABSTRACT: In the present study, the hepatoprotective effect of metformin (Met), a dimethylbiguanide anti-hyperglycemic, was examined in a mouse model of liver damage induced by chronic repeated administration of carbon tetrachloride (CCl4) (5 μl/kg, twice a week for 12 weeks). Met, when given orally in drinking water at an estimated daily dose of 25 or 50 mg/kg for 10 weeks starting 2 weeks after CCl4 challenge, protected against CCl4 hepatotoxicity. The results indicate that the hepatoprotection afforded by Met treatment at a dose of 25 mg/kg against CCl4 toxicity may at least in part be mediated by the enhancement of mitochondrial glutathione redox status.

The 'Yin-Yang' theory is an ancient Chinese philosophy that underlies the practice of traditional Chinese medicine. Although Yang-tonic herbs tend to boost body function possibly through enhancing the mitochondrial oxidative processes, the Yin property (i.e. antioxidant potential) of these herbs can also play a role in safeguarding mitochondrial ATP generation. The pharmacological basis of 'Yang-invigoration' by Chinese tonic herbs might be due primarily to the enhancement of mitochondrial ATP generation.

Outcome expectations of direct pulp capping in carious teeth are obscured by a clinically unknown infiltration and breakdown of the dental pulp tissue. Histologic studies showed that this soft tissue breakdown is related to the innate immune system. We hypothesized 1) that a neutrophil biomarker could predict the outcome of direct pulp capping and 2) that using sodium hypochlorite (NaOCl) as a lavage solution to remove necrotized infected pulp tissue could improve it. In this randomized trial in mature posterior teeth causing no or mild discomfort with carious pulpal exposures, pulpal fluid was collected to assess neutrophil gelatinase (matrix metalloproteinase 9 [MMP-9]) per total protein (TP) levels as a predictive local biomarker. Subsequently, the dentin-pulp wound was randomly washed with a 2.5% NaOCl or a physiologic saline solution (1:1 allocation), capped with mineral trioxide aggregate, and the tooth was immediately restored with a resin-based composite restoration. Ninety-six patients were included, and 84 individuals could be followed up to treatment failure or clinically confirmed pulp survival after a minimum of 1 y. The entire data were fitted to a Cox proportional hazards model to assess the influence of the observational variables MMP-9/TP and discomfort with the randomized lavage treatment on pulp survival. The Kaplan-Meier pulp survival rates after 1 y were 55% for saline and 89% for NaOCl lavage. The inflammatory state of the pulp tissue as reflected by MMP-9/TP levels and NaOCl lavage had a highly significant (P < 0.001 and P = 0.004, respectively) impact on pulp survival, while mild preoperative discomfort did not. In conclusion, MMP-9/TP showed great promise as a predictive local biomarker, and NaOCl lavage considerably improved the survival time of cariously exposed and directly capped pulps. [ABSTRACT FROM AUTHOR]

Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be ‘tipped’ by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between ‘normal’ and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage. [ABSTRACT FROM PUBLISHER]