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Heart failure has reached epidemic proportions in a progressively ageing population. The molecular mechanisms underlying heart failure remain elusive, but evidence indicates that DNA damage is enhanced in failing hearts. Here, we tested the hypothesis that endogenous DNA repair in cardiomyocytes is critical for maintaining normal cardiac function, so that perturbed repair of spontaneous DNA damage drives early onset of heart failure. To increase the burden of spontaneous DNA damage, we knocked out the DNA repair endonucleases xeroderma pigmentosum complementation group G (XPG) and excision repair cross-complementation group 1 (ERCC1), either systemically or cardiomyocyte-restricted, and studied the effects on cardiac function and structure. Loss of DNA repair permitted normal heart development but subsequently caused progressive deterioration of cardiac function, resulting in overt congestive heart failure and premature death within 6 months. Cardiac biopsies revealed increased oxidative stress associated with increased fibrosis and apoptosis. Moreover, gene set enrichment analysis showed enrichment of pathways associated with impaired DNA repair and apoptosis, and identified TP53 as one of the top active upstream transcription regulators. In support of the observed cardiac phenotype in mutant mice, several genetic variants in the ERCC1 and XPG gene in human GWAS data were found to be associated with cardiac remodelling and dysfunction. In conclusion, unrepaired spontaneous DNA damage in differentiated cardiomyocytes drives early onset of cardiac failure. These observations implicate DNA damage as a potential novel therapeutic target and highlight systemic and cardiomyocyte-restricted DNA repair-deficient mouse mutants as bona fide models of heart failure., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: To investigate the effect of calcium hydroxide intracanal medicament on the push-out bond strength of resin-based and calcium silicate-based endodontic sealers., Methods: A comprehensive search of was conducted for all relevant in-vitro studies. All randomized controlled in-vitro studies that evaluated the effect of calcium hydroxide on the push-out bond strength of resin-based or calcium silicate-based endodontic sealers were assessed. The variables of interest were extracted, and the risk of the included studies was evaluated. The standardized mean difference was calculated and the significance level was set at p value <0.05., Results: A total of 26 studies were eligible for analysis. There were 45 independent comparison groups and 1009 recruited teeth. The pooled data showed no significant difference in push-out bond strength between calcium hydroxide and control group in the resin-based group (SMD = 0.03; 95% CI = -0.55, 0.60; p = 0.93), and calcium silicate-based group (SMD = 0.02; 95% CI = -0.31, 0.35; p = 0.90). Most of the studies (21 out of 26) were at medium risk of bias and five studies showed a low risk of bias., Conclusion: The available evidence suggests that calcium hydroxide used as intracanal medication does not influence the push-out bond strength of the resin- and calcium silicate-based endodontic sealers., Clinical Significance: The results of this meta-analysis suggest that calcium hydroxide used as intracanal medication does not influence the push-out bond strength of resin-based and calcium silicate-based endodontic sealers., (© 2022 Wiley Periodicals LLC.)

Purpose: The fracture resistance of dental post systems is influenced by the material of the post. The purpose of this systematic review and meta-analysis was to assess if there is a difference in fracture resistance between prefabricated dental titanium posts and fiber posts., Methods: An online electronic search was performed using the PubMed, Scopus, and Web of Science databases for in vitro studies published from 2010 to 2020 in English. The retrieved eligible studies that compared the fracture resistance of titanium and fiber posts on human teeth were selected. The pooled standardized mean difference (SMD) with a 95% confidence interval was calculated. In addition, the trial sequential analysis (TSA) was performed to test if the available studies are sufficient to make conclusive evidence., Results: Of the 1165 retrieved studies, 17 studies were included in the qualitative analysis, while 16 studies were included in the quantitative analysis. Because of the high heterogeneity among studies, data from 10 studies were pooled and submitted to TSA. A total of 852 teeth were evaluated for fracture of the posts in 27 independent comparison groups. The pooled effect of the residual studies revealed no significant difference between titanium and fiber posts (SMD = -0.12; 95% CI = -0.30, 0.06; p = 0.20). Results of the TSA revealed no conclusive evidence., Conclusions: The results of the current evidence revealed no significant difference between fiber and titanium posts. The evidence is insufficient, and more standardized in vitro studies are required., (© 2021 by the American College of Prosthodontists.)

Purpose: This systematic review aims to identify and interpret results of studies that evaluated the changes in the physical properties of maxillofacial prosthetic materials (1) without aging, (2) after natural or artificial accelerated aging, and (3) after outdoor weathering., Methods: Relevant articles written in English only, before January 15, 2017, were identified using an electronic search in the PubMed, Scopus, and Google Scholar databases. Furthermore, a manual search of the related major journals was also conducted to identify more pertinent articles. The relevancy of the articles was verified by screening the title, abstract, and full text if they met the inclusion criteria. A total of 37 articles satisfied the criteria, from which data were extracted for qualitative synthesis., Results: Among the 37 included articles, 14 were without aging, 15 were natural or artificial accelerated aging, 7 were outdoor weathering, and 1 contained both artificial aging and outdoor weathering. Only 4 studies out of the 14 without aging had significant observations; whereas 9 articles with natural or artificial aging published significant results, and 3 out of 7 outdoor weathering articles showed significant changes in the evaluated silicone elastomers., Conclusions: Despite the varying research, it seems that the single "ideal" maxillofacial prosthetic material that can provide sufficient resistance against different aging conditions is yet to be identified. Therefore, it is imperative for standardization organizations, the scientific community, and academia to develop modified prosthetic silicones possessing improved physical properties and color stability, limiting the clinical problems regarding degradation of maxillofacial prostheses., (© 2018 by the American College of Prosthodontists.)

The use of doxorubicin (DOXO) as a chemotherapeutic drug has been hampered by cardiotoxicity leading to cardiomyopathy and heart failure. Folic acid (FA) is a modulator of endothelial nitric oxide (NO) synthase (eNOS), which in turn is an important player in diseases associated with NO insufficiency or NOS dysregulation, such as pressure overload and myocardial infarction. However, the role of FA in DOXO-induced cardiomyopathy is poorly understood. The aim of this study was to test the hypothesis that FA prevents DOXO-induced cardiomyopathy by modulating eNOS and mitochondrial structure and function. Male C57BL/6 mice were randomized to a single dose of DOXO (20 mg/kg intraperitoneal) or sham. FA supplementation (10 mg/day per oral) was started 7 days before DOXO injection and continued thereafter. DOXO resulted in 70% mortality after 10 days, with the surviving mice demonstrating a 30% reduction in stroke volume compared with sham groups. Pre-treatment with FA reduced mortality to 45% and improved stroke volume (both P < 0.05 versus DOXO). These effects of FA were underlain by blunting of DOXO-induced cardiomyocyte atrophy, apoptosis, interstitial fibrosis and impairment of mitochondrial function. Mechanistically, pre-treatment with FA prevented DOXO-induced increases in superoxide anion production by reducing the eNOS monomer:dimer ratio and eNOS S-glutathionylation, and attenuated DOXO-induced decreases in superoxide dismutase, eNOS phosphorylation and NO production. Enhancing eNOS function by restoring its coupling and subsequently reducing oxidative stress with FA may be a novel therapeutic approach to attenuate DOXO-induced cardiomyopathy., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)