Graphene oxide has attracted widespread attention in the biomedical fields due to its excellent biocompatibility. Herein we investigated the layer-number dependent antibacterial and osteogenic behaviors of graphene oxide in biointerfaces. Graphene oxide with different layer numbers was deposited on the titanium surfaces by cathodal electrophoretic deposition with varied deposition voltages. The initial cell adhesion and spreading, cell proliferation, and osteogenic differentiation were observed from all the samples using rat bone mesenchymal stem cells. Both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus were used to investigate the antibacterial effect of the modified titanium surfaces. Cocultures of human gingival fibroblasts (HGF) cells with Escherichia coli and Staphylococcus aureus were conducted to simulate the conditions of the clinical practice. The results show that the titanium surfaces with graphene oxide exhibited excellent antibacterial and osteogenic effects. Increasing the layer-number of graphene oxide resulted in the augment of reactive oxygen species levels and the wrinkling, which led to the antibacterial and osteogenic effects, respectively. Compared to pure titanium surface in the cells-bacteria coculture process, the modified titanium surfaces with graphene oxide exhibited higher surface coverage percentage of cells.

Background Apical periodontitis (AP) is essentially an inflammatory disease of microbial etiology primarily caused by infection of the pulp and root canal system. Variation of the bacterial communities caused by AP, as well as their changes responding to dental therapy, are of utmost importance to understand the pathogensis of the apical periodontitis and establishing effective antimicrobial therapeutic strategies. This study aims to uncover the composition and diversity of microbiota associated to the root apex to identify the relevant bacteria highly involved in AP, with the consideration of root apex samples from the infected teeth (with/without root canal treatment), healthy teeth as well as the healthy oral. Methods Four groups of specimens are considered, the apical part of root from diseased teeth with and without root canal treatment, and wisdom teeth extracted to avoid being impacted (tooth healthy control), as well as an additional healthy oral control from biofilm of the buccal mucosa. DNA was extracted from these specimens and the microbiome was examined through focusing on the V3-V4 hypervariable region of the 16S rRNA gene using sequencing on Illumina MiSeq platform. Composition and diversity of the bacterial community were tested for individual samples, and between-group comparisons were done through differential analysis to identify the significant changes. Results We observed reduced community richness and diversity in microbiota samples from diseased teeth compared to healthy controls. Through differential analysis between AP teeth and healthy teeth, we identified 49 OTUs significantly down-regulated as well as 40 up-regulated OTUs for AP. Conclusion This study provides a global view of the microbial community of the AP associated cohorts, and revealed that AP involved not only bacteria accumulated with a high abundance, but also those significantly reduced ones due to microbial infection. Electronic supplementary material The online version of this article (10.1186/s12864-019-5474-y) contains supplementary material, which is available to authorized users.

Titanium and its alloys have been widely used in orthopedic and dental implants because of their excellent properties. However, implant failures still occur due to implant-associated bacterial infections. Therefore, proper surface modification of titanium and its alloys is necessary. In this work, commercial pure titanium plates were modified with graphene oxide (GO) which was used to load minocycline hydrochloride. Gram-positive Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans) and Gram-negative Escherichia coli (E. coli) were used to investigate the antibacterial activity of the samples. Human gingival fibroblast (HGF) cells were applied to assess the cytocompatibility of the various samples. To investigate cell adhesion and cell surface coverage in the presence of bacteria, the coculture of HGF cells and S. aureus was performed. The results indicated that the GO-modified titanium surface could inhibit the growth of the bacteria which had direct contact with GO, while it could not affect the bacteria without direct contact of GO. Minocycline hydrochloride on the GO-modified titanium surface (M@GO-Ti) showed a slow release behavior and exhibited excellent antibacterial activity with the synergistic effect of contact-killing and release-killing by GO and minocycline hydrochloride, respectively. In the coculture process with the presence of S. aureus, HGF cells on M@GO-Ti demonstrated the best cell viability and cell surface coverage among all the samples.

These findings strongly suggested that luteolin suppresses H(2) O(2) -directed migration and proliferation in VSMCs partially due to down-regulation of the Akt and Src signalling pathways, which are important participants in the processes of migration and proliferation of VSMCs.

NLRP3, a member of the nucleotide-binding oligomerization domain (NOD)-like receptor family, is involved in cardiac inflammation. However, the functional role of NLRP3 in cardiac remodeling is not clear. To investigate the roles of NLRP3 in pressure overload-induced cardiac remodeling, NLRP3 knockout and wild-type mice were subjected to aortic banding to induce cardiac remodeling. The data showed that NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated cardiac hypertrophy, fibrosis, and inflammation responses with deteriorating cardiac dysfunction in the pressure overload-induced cardiac remodeling mouse model. Neonatal rat cardiomyocytes were isolated and stimulated with phenylephrine (PE). We identified NLRP3 as a negative regulator of cardiomyocyte remodeling in PE-stimulated cardiomyocyte remodeling using adenovirus-NLRP3 and NLRP3 siRNA. Mechanistically, we found that the expression of Toll-like receptor (TLR) 4 was upregulated in NLRP3-deficient mouse hearts and PE-stimulated cardiomyocytes. NLRP3 knockout mice subjected to a TLR4 inhibitor revealed a relieved cardiac remodeling response with improved cardiac dysfunction. Our data suggested that NLRP3 could be a therapeutic target for cardiac remodeling and heart failure. KEY MESSAGES: NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated pressure overload-induced cardiac remodeling. NLRP3 acted as a negative regulator of cardiomyocyte remodeling via downregulating TLR4.

Background/Aims: Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a cytoplasmic protein, involved in autoimmune diseases, mammalian reproduction, neuronal cell death, and stroke. However, the role of NLRP1 in cardiac hypertrophy remains unclear. We used in vivo and in vitro models to investigate the effects of NLRP1 on cardiac hypertrophy. Methods: We used NLRP1-deficient mice and cultured neonatal rat cardiomyocytes with gain and loss of NLRP1 function. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements, and by pathological and molecular analysis. Results: Eight weeks after aortic banding (AB), NLRP1 deficiency significantly inhibited aortic banding–induced cardiac hypertrophy, inflammation, and fibrosis. Activation of MAPK, NF-κB, and TGF-β/Smad pathways was reduced in NLRP1-knockout (KO) mice compared with that in wild-type (WT) mice. Consistent with these results, in vitro studies, performed using cultured neonatal mouse cardiomyocytes, confirmed that NLRP1 deficiency protects against cardiomyocyte hypertrophy induced by isoproterenol (PE); this protective activity was associated with the arrest of MAPK and NF-κB signaling. Conclusions: Our data illustrates that NLRP1 plays a crucial role in the development of cardiac hypertrophy via positive regulation of the MAPK, NF-κB, and TGF-β/Smad signaling pathways.

Recent studies have demonstrated that ginsenoside Rb1 protects the myocardium from ischemia-reperfusion (I/R) injury. However, the precise mechanisms for this protection have not been determined. This study aimed to determine whether the attenuation of I/R-induced myocardial injury by ginsenoside Rb1 (GS Rb1) is due to inhibition of p38α mitogen-activated protein kinase (MAPK). Sprague-Dawley rats were distributed among 6 treatment groups: sham group; I/R group; p38 MAPK inhibitor SB203580 group (SB + I/R); GS Rb1 group (GS + I/R); p38 MAPK agonist anisomycin group (Ani + I/R); and the GS Rb1 + Ani group (GS + Ani + I/R). All of the anaesthetized rats, except those in the sham group, underwent an open-chest procedure that involved 30 min of myocardial ischemia followed by 2 h of reperfusion. Myocardial infarction size (MIS), caspase-3 activity, and levels of the cytokine tumor necrosis factor alpha (TNF-α) in the myocardium were monitored. The expressions of p38α MAPK, caspase-3, and TNF-α in the myocardium were assayed. GS Rb1 reduced MIS and attenuated caspase-3 activity and the levels of TNF-α in the myocardium. Protein expression of total p38α MAPK was not significantly altered. In the Ani + I/R and I/R groups, the levels of phospho-p38α MAPK were significantly increased compared with the sham group, and these increased levels were reduced with GS Rb1. Hemodynamic parameters were not significantly different between the GS + I/R and SB + I/R groups. GS Rb1 exerts an anti-apoptotic effect that protects against I/R injury by inhibiting p38α MAPK phosphorylation, suggesting that GS Rb1-mediated protection requires the inhibition of p38α MAPK.

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