Diverse types of dental adhesives exhibit different cytotoxic outcomes on cells in vitro. Currently, no standard adhesive application technique has so far been decisive for clinicians for better durability of resin-dentin bonds of adhesive systems. The purpose of this study was to systematically review the literature to evaluate the bonding performance of adhesive systems to dentin by using different application modalities. The systematic research strategy was conducted by two reviewers among multiple databases: PubMed, Scopus, Web of Science, Embase, and Scielo. In vitro studies reporting the effects of additional steps for the application of adhesive systems on the bond strength to dentin were selected. Meta-analysis was performed using Review Manager Software version 5.3.5 using the random effects model. The methodological quality of each in vitro study was assessed according to the parameters of a previous systematic review. The electronic research through different databases generated a total of 8318 references. After the examination of titles and abstracts, a total of 106 potentially relevant studies accessed the full-text evaluation phase. After full-text examination, 78 publications were included for the qualitative analysis, and 68 studies were included in the meta-analysis. Regarding the etch-and-rinse adhesive systems, the application modalities that improved the overall bond strength were the application of a hydrophobic resin layer (p = 0.005), an extended application time (p < 0.001), an application assisted by an electric current (p < 0.001), a double-layer application (p = 0.05), the agitation technique (p = 0.02), and the active application of the adhesive (p < 0.001). For self-etch adhesive systems, the techniques that improved the overall bond strength were the application of a hydrophobic resin layer (p < 0.001), an extended application time (p = 0.001), an application assisted by an electric current (p < 0.001), a double-layer application (p < 0.001), the agitation technique (p = 0.01), and the active application of the adhesive (p < 0.001). The in vitro evidence suggests that the application of adhesive systems using alternative techniques or additional strategies may be beneficial for improving their bond strength to dentin. The application modalities that favored the overall bond strength to dentin were an extended application time, a double-layer application, an application assisted by an electric current, the active application of the adhesive, and the application of a hydrophobic resin layer. Worth mentioning is that some techniques are intended to increase the degree of the conversion of the materials, and therefore, improvements in the biocompatibility of the materials can be expected.

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) causes porcine pleuropneumonia that seriously endangers pig's health. Adh, located in the head region of trimeric autotransporter adhesion of A. pleuropneumoniae, affects bacterial adhesion and pathogenicity. However, how Adh mediates A. pleuropneumoniae immune invasion is still unclear. Here, we established the A. pleuropneumoniae strain L20 or L20 Delta Adh-infected porcine alveolar macrophages (PAM) model, and applied protein overexpression, RNA interference, qRT-PCR, Western blot and immunoflourescence techniques to dissect the effects of Adh on PAM during A. pleuropneumoniae infection. We found that Adh could increase the A. pleuropneumoniae adhesion and intracellular survival in PAM. Gene chip analysis of piglet lungs further showed that Adh significantly induced cation transport regulatory-like protein 2 (CHAC2) expression, whose overexpression suppressed the phagocytic capacity of PAM. Furthermore, CHAC2 overexpression dramatically increased glutathione (GSH) expression, decreased reactive oxygen species (ROS), and promoted A. pleuropneumoniae survival in PAM, while the knockdown of CHAC2 reversed these phenomena. Meanwhile, CHAC2 silence activated the NOD1/NF-kappa B pathway, resulting in an increase in IL-1 beta, IL-6, and TNF-alpha expression, whereas this effect was weakened by CHAC2 overexpression and addition of NOD1/NF-kappa B inhibitor ML130. Moreover, Adh enhanced the secretion of LPS of A. pleuropneumoniae, which regulated the expression of CHAC2 via TLR4. In conclusion, through a LPS-TLR4-CHAC2 pathway, Adh inhibits respiratory burst and inflammatory cytokines expression to promote A. pleuropneumoniae survival in PAM. This finding may provide a novel target for the prevention and treatment of A. pleuropneumoniae.

Acute kidney injury (AKI) leads to acute cardiac injury and dysfunction in cardiorenal syndrome Type 3 (CRS3) through oxidative stress (OS). The stress-inducible Sestrin2 (Sesn2) protein reduces reactive oxygen species (ROS) accumulation and activates AMP-dependent protein kinase (AMPK) to regulate cellular metabolism and energetics during OS. Sesn2 levels and its protective effects decline in the aged heart. Antidiabetic drug metformin upregulates Sesn2 levels in response to ischemia-reperfusion (IR) stress. However, the role of metformin in CRS3 remains unknown. This study seeks to explore how the age-related decrease in cardiac Sesn2 levels contributes to cardiac intolerance to AKI-induced insults, and how metformin ameliorates CRS3 through Sesn2. Young (3-5 months) and aged (21-23 months) C57BL/6J wild-type mice along with cardiomyocyte-specific knockout (cSesn2(-/)(-)) and their wild type of littermate (Sesn2(f/f)) C57BL/6J mice were subjected to AKI for 15 min followed by 24 h of reperfusion. Cardiac and mitochondrial functions were evaluated through echocardiograms and seahorse mitochondria respirational analysis. Renal and cardiac tissue was collected for histological analysis and immunoblotting. The results indicate that metformin could significantly rescue AKI-induced cardiac dysfunction and injury via Sesn2 through an improvement in systolic and diastolic function, fibrotic and cellular damage, and mitochondrial function in young, Sesn2(f/f), and especially aged mice. Metformin significantly increased Sesn2 expression under AKI stress in the aged left-ventricular tissue. Thus, this study suggests that Sesn2 mediates the cardioprotective effects of metformin during post-AKI.