Role of macrophage polarization in periodontitis promoting atherosclerosis.

Periodontitis is a chronic inflammatory destructive disease occurring in periodontal supporting tissues. Atherosclerosis(AS) is one of the most common cardiovascular diseases. Periodontitis can promote the development and progression of AS. Macrophage polarization is closely related to the development and progression of the above two diseases, respectively. The purpose of this animal study was to evaluate the effect of periodontitis on aortic lesions in atherosclerotic mice and the role of macrophage polarization in this process. 45 ApoE-/-male mice were randomly divided into three groups: control (NC), atherosclerosis (AS), and atherosclerosis with periodontitis (AS + PD). Micro CT, serological testing and pathological testing(hematoxylin-eosin staining, oil red O staining and Masson staining) were used for Evaluate the modeling situation. Immunohistochemistry(IHC) and immunofluorescence(IF) were performed to evaluate macrophage content and macrophage polarization in plaques. Cytokines associated with macrophage polarization were analyzed using quantitative real-time polymerase chain reaction(qRT-PCR) and enzyme-linked immunosorbent assay(Elisa). The expression of macrophages in plaques was sequentially elevated in the NC, AS, and AS + PD groups(P < 0.001). The expression of M1 and M1-related cytokines showed the same trend(P < 0.05). The expression of M2 and M2-related cytokines showed the opposite trend(P < 0.05). The rate of M1/M2 showed that AS + PD > AS > NC. Our preliminary data support that experimental periodontitis can increase the content of macrophage in aortic plaques to exacerbate AS. Meanwhile, experimental periodontitis can increase M1 macrophages, and decrease M2 macrophages, increasing M1/M2 in the plaque.

Investigation of the mechanism of baicalein in the treatment of periodontitis based on network pharmacology, molecular docking and experimental validation.

PURPOSE: To verify the effect and mechanism of baicalein in the treatment of periodontitis through network pharmacology, molecular docking and in vitro experiments. METHODS: Firstly, multiple databases were used to predict targets of baicalein and periodontitis. And the screened key target genes of baicalein for treating periodontitis were subjected to GO and KEGG analysis; then these targets were analyzed by molecular docking techniques. In vitro experiments including CCK-8, RT-qPCR, ELISA and Immunofluorescence were conducted to validate the efficacy of baicalein in treating periodontitis. RESULTS: Seventeen key targets were screened from the databases, GO and KEGG analysis of these targets revealed that baicalein may exert therapeutic effects through regulating TNF, PI3K-Akt, HIF-1 and other signaling pathways. Molecular docking analysis showed that baicalein has good binding potential to several targets. In vitro cellular assays showed that baicalein inhibited the expression of TNF-α, MMP-9, IL-6 and MCP1 in P.g-LPS-induced macrophages at both the mRNA and protein level. And the immunofluorescence intensity of iNOS, a marker of M1 type macrophages, which mainly secretes inflammatory factors, was significantly reduced. CONCLUSION: Baicalein has the characteristics and advantages of "multicomponent, multitarget, and multipathway" in the treatment of periodontitis. In vitro cellular assays further confirmed the inhibitory effect of baicalein on the secretion of inflammatory factors of macrophages in periodontitis models, providing a theoretical basis for further study of the material basis and molecular mechanism of baicalein in the treatment of periodontal diseases.

Study on the effect of periodontitis on renal tissue in atherosclerotic mice.

BACKGROUND AND OBJECTIVE: Periodontitis is immune inflammatory disease, atherosclerosis (AS) and chronic kidney disease (CKD) are two common systemic diseases. Periodontitis promotes AS and CKD, and CKD interacts with AS. The objective of this animal study was to evaluate the changes of kidney when periodontitis and atherosclerosis exist separately and the degenerative effects of periodontitis on the kidney in atherosclerotic mice. MATERIALS AND METHODS: A total of 40 male Apoe-/- mice were randomly divided into four groups: control (NC), periodontitis (PD), AS and AS with PD (AS + PD). AS was induced by high-fat diet feeding, and PD was induced by injection of Porphyromonas gingivalis-Lipopolysaccharide (P.g-LPS) (endotoxin suspension) into the buccal side of mouse maxillary molars. The right maxilla of mice was scanned with micro-CT to evaluate alveolar bone loss; aortic tissue was stained with HE and Oil-Red O to evaluate arterial plaque formation; serum was collected to detect the changes of blood lipids and serum renal function parameters (blood urea nitrogen [BUN], serum creatinine [Scr]); renal histopathological changes were evaluated by HE staining (glomerular and tubular damage scores), PAS staining (glomerular Mesangial matrix index) and Masson staining (percentage of renal fibrosis area); qRT-PCR and ELISA were used to evaluate the expression of renal inflammatory cytokines (tumor necrosis factor-α, Interleukin-1ß, neutrophil surface marker Ly6G). RESULTS: The amount of alveolar bone loss: PD group was significantly higher than NC group (p < .05); AS + PD group was higher than PD group, the difference was not statistically significant. Atherosclerotic plaque formation and serum lipid changes: AS group were significantly worse than NC group (p < .05), and AS + PD group were worse than AS group. The results of the corresponding qualitative and quantitative analyses of kidney tissue in experimental animals gradually deteriorated in the NC group, PD group, AS group and AS + PD group and worsened sequentially. Renal function parameters: the content of BUN in AS group was higher than that in PD group, the difference was not statistically significant; Scr in AS group was significantly higher than that in PD group (p < .05); the contents of BUN and Scr in AS + PD group were higher than those in AS group, the difference was not statistically significant. Glomerular and tubular damage scores: AS group were higher than PD group, the difference was not statistically significant; AS + PD group were significantly higher than AS group (p < .001). The ratio of glomerular mesangial matrix to glomerular area and the percentage of renal fibrosis area: AS group were significantly higher than PD group (p < .001), and AS + PD group were significantly higher than AS group (p < .001). Expression of inflammatory cytokines: AS group was higher than PD group, the difference was not statistically significant; AS + PD group was significantly higher than AS group (p < .05). CONCLUSION: Both PD and AS can aggravate the inflammatory stress of kidney tissue and cause the damage of kidney tissue, and the inflammatory increase and damage effect of AS is stronger; PD can promote kidney damage of atherosclerotic mice by aggravating the renal inflammation in atherosclerotic mice; renal function parameters were not completely synchronized with the changes of renal inflammation and histopathology in each group of mice; PD can promote AS, periodontal inflammation in mice with AS is more severe, and the special changes of blood lipids in mice with AS are closely related to the above results.

Altered dental plaque microbiota correlated with salivary inflammation in female methamphetamine users.

Poor oral health is the most immediate and overlooked hazard of methamphetamine abuse in humans. Previous studies have reported methamphetamine-associated alterations in saliva microbiota, but the cause of methamphetamine-induced alterations in the oral microenvironment remains unclear. The present study aimed to investigate the alterations in dental plaque microbiota in methamphetamine users, and to explore their relationship with local immune inflammation in the oral cavity. This may provide new ideas on the development of methamphetamine-related oral microenvironment changes. Questionnaires and samples were obtained from 30 female methamphetamine users and 15 sex- and age-matched healthy controls. Microbial profiles of supragingival dental plaque were analyzed using 16S rRNA gene sequencing. Inflammatory factors in saliva were measured using enzyme-linked immunosorbent assay. Methamphetamine users had worse oral self-evaluation. Compared with healthy controls, methamphetamine users showed no differences in oral dental plaque microbial diversity but exhibited differences in the relative abundance of several microbial taxa. At the phylum level, a higher abundance of Proteobacteria and a lower abundance of Firmicutes were detected in methamphetamine users. Moreover, function prediction using the MetaCyc database showed that 33 pathways were significantly upregulated in methamphetamine users; Only the glycolytic (Pyrococcus) pathway was enriched in the C group. Importantly, salivary inflammatory factors showed complex significant associations with bacterial genera in methamphetamine users. Specifically, the genus Neisseria was positively correlated with IL-17 levels in saliva, and both were high in methamphetamine users. In contrast, the genus Streptococcus, with a lower abundance, was positively correlated with lower IL-10 levels. Overall, This study is the first to provide evidence for a link between altered dental plaque microbiota and salivary inflammation in methamphetamine users. Further elucidation of the interactions between methamphetamine use and oral microenvironment would be beneficial for appropriate interventions to improve oral health.

Bio-Inspired Instant Underwater Adhesive Hydrogel Sensors.

Underwater adhesion plays an essential role in soft electronics for the underwater interface. Although hydrogel-based electronics are of great interest, because of their versatility, water molecules prevent hydrogels from adhering to substrates, thus bottlenecking further applications. Herein, inspired by the barnacle proteins, MXene/PHMP hydrogels with strong repeatable underwater adhesion are developed through the random copolymerization of 2-phenoxyethyl acrylate, 2-methoxyethyl acrylate, and N-(2-hydroxyethyl) acrylamide with the presence of MXene nanosheets. The hydrogels are mechanically tough (elastic modulus of 32 kPa, fracture stress of 0.11 MPa), and 2-phenoxyethyl acrylate (PEA) with aromatic groups endows the hydrogel with nonswelling property and prevents water molecules from invading the adhesive interface, rendering the hydrogels an outstanding adhesive behavior toward various substrates (including glass, iron, polyethylene terephthalate (PET), porcine). Besides, dynamic physical interactions allow for instant and repeatable underwater adhesion. Furthermore, the MXene/PHMP hydrogels exhibit a high conductivity (0.016 S/m), fast responsiveness, and superior sensitivity as a strain sensor (gauge factor = 7.17 at 200%-500% strain) and pressure sensor (0.63 kPa-1 at 0-70 kPa). The underwater applications of bionic hydrogel-based sensors have been demonstrated, such as human motion, pressure sensing, and holding objects. It is anticipated that the instant and repeatable underwater adhesive hydrogel-based sensors extend the underwater applications of hydrogel electronics.

An Intrapericardial Injectable Hydrogel Patch for Mechanical-Electrical Coupling with Infarcted Myocardium.

Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.