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.

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.

Implementation of blind source separation for optical fiber sensing.

Blind source separation (BSS) is implemented for optical fiber sensing systems, such as the fiber Bragg grating (FBG) sensing system and the single-mode-multimode-single-mode fiber (SMS) sensing system. The FastICA, a kind of multichannel BSS algorithm, is used to get the strain and the temperature with two FBGs. For the SMS sensing, a single-channel blind source separation (SCBSS) algorithm is employed to simultaneously measure the vibration and the temperature variation with only one SMS sensor. The errors of both the FBG and the SMS optical fiber sensing system are very small with the BSS algorithm. The implementation of BSS for the optical fiber sensing makes the multiparameter measurements more easily with low cost and high accuracy and can also be applied for signal de-noising field.

Revealing the active ingredients and mechanism of P. sibiricumm in non-small-cell lung cancer based on UPLC-Q-TOF-MS/MS, network pharmacology, and molecular docking.

The alcohol extraction of P. sibiricum has exhibited significant inhibitory effects on the production of free radicals and the proliferation of non-small-cell lung carcinoma (NSCLC) A549 cells. Despite the diverse components found in alcohol extraction of P. sibiricum and its multiple targets, the active components and associated targets remain largely unidentified. Hence, there is a need for additional investigation into the pharmacodynamic elements and mechanisms of action. This study aimed to analyze and identify the components responsible for the anti-tumor activity of alcohol extraction from P. sibiricum using UPLC-Q-TOF-MS/MS for the first time. Subsequently, the targets of the active components were predicted using the SwissTargetPrediction database, whereas the targets for NSCLC were sourced from the Online Mendelian Inheritance in Man database (OMIM) and the GeneCards database. Next, the targets of chemical composition were integrated with disease targets via Venny online. GO and KEGG pathway enrichment analyses were performed utilizing DAVID. Subsequently, a network analysis of "components-targets-pathways" was established using Cytoscape 3.8.2 and assessed with the "network analyzer" plug-in. Molecular docking was conducted utilizing Autodock 1.5.6. The study aimed to examine the anti-proliferative impacts and underlying mechanisms of alcohol extraction from P. sibiricum on NSCLC through in vivo and in vitro investigations utilizing an animal model of transplanted tumor, CCK8 assay, cell scratch test, RT-qPCR, and western blotting. The study unveiled that 17 active components extracted from P. sibiricum alcohol demonstrated anti-non-small cell lung cancer (NSCLC) effects through the modulation of 191 targets and various significant signaling pathways. These pathways include Endocrine resistance, PI3K/AKT, Chemical carcinogenesis-receptor activation, Proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, AMPK signaling pathway, and other related signaling pathways. Network analysis and molecular docking results indicated that specific compounds such as (25S)-26-O-(ß-d-glucopyranosyl)-furost-5-en3ß,22α,26-triol3-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl-(1→4)-ß-d-glucopyranoside, Timosaponin H1, Deapi-platycodin D3, (3R)-5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxybenzyl)-chroman-4-one, Disporopsin, Funkioside F, Kingianoside E, Parisyunnanoside H, and Sibiricoside B primarily targeted 17 key proteins (BCL2, EGFR, ESR1, ESR2, GRB2, IGF1R, JUN, MAP2K1, MAPK14, MAPK8, MDM2, MMP9, mTOR, PIK3CA, RAF1, RPS6KB1, and SRC) collectively. In conclusion, the alcohol extraction of P. sibiricum demonstrated inhibitory effects on cell proliferation, induction of apoptosis, and inhibition of metastasis through various pathways.

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.

Erratum: Focused ultrasound-augmented targeting delivery of nanosonosensitizers from homogenous exosomes for enhanced sonodynamic cancer therapy: Erratum.

[This corrects the article DOI: 10.7150/thno.33183.].

[A finite element study of the influence of upper lip pressure on the development of maxilla after cleft lip surgery].

PURPOSE: To explore the mechanism of upper lip pressure on maxilla after cleft lip surgery. METHODS: ANSYS 17.0 software was used to add the upper lip soft tissue to the finite element model of maxilla with cleft palate, and the material properties was assigned to form a three-dimensional finite element model of maxilla with upper lip. The upper lip pressure was applied to the model and force analysis was performed in 2 groups. In the experimental group, upper lip pressure with cleft lip surgery was applied; in the control group, upper lip pressure in normal children of the same age was applied. RESULTS: Maxillary deformation in the experimental group was greater than that in the control group. Maxillary deformation occurred in three-dimensional direction, which was mainly in Z axis, followed by X axis and Y axis. The anterior segment of alveolar process was the most obvious，and from the anterior to the posterior, the change trend was gradually decreased. CONCLUSIONS: Maxillary growth is inhibited in three-dimensional direction,which is mainly sagittal growth inhibition,followed by transverse and vertical growth. The inhibition gradually decreases from anterior to posterior.

Hypocrellin B triggered sonodynamic therapy reverses multidrug resistance of doxorubicin-resistant SGC7901/ADR cells via down-regulation of P-gp expression.

The combating of multidrug resistance (MDR) plays a crucial role in effective chemotherapy. However, current strategies for cancer of MDR remain unsatisfactory for their limited efficacy and severe side effects. In this study, we sought to determine the anti-MDR effects of a traditional chinese herb, Hypocrellin B (HB)-mediated sonodynamic therapy (HB-SDT) on human gastric multidrug resistance cancer SGC-7901cell/ADR cells and its underlying mechanisms. HB-SDT can synergistically increase the cytotoxicity of DOX on SGC-7901cell/ADR cells in which the mechanism is related to significant promotion of apoptosis, ROS level and drop of MMP in the resistant cells after combining treatment of DOX and HB-SDT. Meanwhile, western blotting assays display the expression of apoptosis related proteins Bax and Bcl-2 changed markedly after the combination treatment. In addition, the expression of P-gp was significantly down-regulated after treatment of HB-SDT and DOX. HB-SDT can increase DOX-induced mitochondrial-dependent apoptosis by inhibiting the expression of P-gp, thereby increasing the cytotoxic effect into SGC7901/ADR cells.

[Finite element analysis of the comprehensive impact of scar and maxillary expansion combined with protraction on the development of maxilla with cleft lip and palate after repair operation].

OBJECTIVE: To study the comprehensive impact of scar and maxillary expansion combined with protraction on the development of maxilla with cleft lip and palate after repair operation. METHODS: In the original finite element model of the maxilla with cleft palate, a finite element model of the maxilla with cleft lip and palate was established by using Boolean operation in ANSYS. Scar force after cleft lip and palate repair and maxillary expansion force combined with protraction were added simultaneously to process the stress analysis. RESULTS: Maxillary deformation occurred in the three-dimensional direction. The comparison of displacements was as follows: X-axis>Z-axis>Y-axis. CONCLUSIONS: Maxillary growth is significantly inhibited in the three-dimensional direction under the comprehensive impact of scar and maxillary expansion combined with protraction after repair operation, especially transverse and sagittal growth.

Azo-based near-infrared fluorescent theranostic probe for tracking hypoxia-activated cancer chemotherapy in vivo.

A novel azo-based near-infrared fluorescent theranostic probe was synthesized, which is selectively activated under hypoxic conditions, resulting in the release of an active anticancer drug and a near-infrared fluorophore turn-on. Notably, the probe has been applied successfully to real-time visualization of drug delivery in 4T1, HepG2 cells, and mice.

Ultrasound Facilitates Naturally Equipped Exosomes Derived from Macrophages and Blood Serum for Orthotopic Glioma Treatment.

Exosomes (Exos) are endogenous nanocarriers that have utility as novel delivery systems for the treatment of brain cancers. However, in general, natural Exos show limited BBB-crossing capacity and lack specific targeting. Further modifications including targeting peptides and genetic engineering approaches can circumvent these issues, but the process is time-consuming. Focused ultrasound (FUS) has been approved by the Food and Drug Administration for the diagnosis and treatment of brain diseases due to its noninvasive nature, reversibility, and instantaneous local opening of the BBB. In this study, we developed a natural and safe transportation system using FUS to increase the targeted delivery of Exos for glioma therapy. We also compared the advantages of macrophage-derived Exos (R-Exos) and blood serum-derived Exos (B-Exos) to screen for an improved platform with scope for clinical transformation. In vitro, both R-Exos and B-Exos were transported through BBB models and accumulated in glioma cells with the assistance of ultrasound exposure. R-Exos and B-Exos displayed no obvious differences in physical characteristics, drug release, tumor targeting, and cytotoxicity when combined with FUS. In vivo animal imaging studies suggested that the fluorescence intensity of B-Exos plus single FUS in brains was 4.45-fold higher than that of B-Exos alone. Furthermore, B-Exos plus twice FUS treatment efficiently suppressed glioma growth with no obvious side effects. We therefore demonstrate that the combination of FUS and naturally abundant B-Exos is a potent strategy for brain cancer therapeutics.

Focused ultrasound-augmented targeting delivery of nanosonosensitizers from homogenous exosomes for enhanced sonodynamic cancer therapy.

Sonodynamic therapy (SDT), wherein focused ultrasound is used to guide the site-specific delivery of nano-sonosensitizers and trigger profound sono-damage, has great potential in cancer theranostics. The development of nanosensitizers with high sono-activatable efficiency and good biosafety is however challenging. Methods: In this study, we designed a functionalized smart nanosonosensitizer (EXO-DVDMS) by loading sinoporphyrin sodium (DVDMS), an excellent porphyrin sensitizer with both potential therapeutic and imaging applications, onto homotypic tumor cell-derived exosomes. Because of the high binding-affinity between DVDMS and proteins, coincubation of DVDMS and exosome would result in DVDMS attached on the surface or loaded in the core of exosomes. The prepared EXO-DVDMS was applied for ultrasound-responsive controlled release and enhanced SDT. Results: Tumor cell-derived exosomes exhibited high stability and specificity towards the homotypic tumors, along with highly controlled ultrasound-responsive drug release, and boosted reactive oxygen species (ROS) generation to augment SDT. Intriguingly, EXO-DVDMS was endocytosed by lysosomes, and the low pH in the latter triggered DVDMS relocation synergistically with the ultrasound, thereby initiating multiple cell death-signaling pathways. Furthermore, the exosomal formulation served as a functionalized nanostructure, and facilitated simultaneous imaging and tumor metastasis inhibition, that were respectively 3-folds and 10-folds higher than that of free form. Conclusions: Taken together, our findings suggest that an extracorporeal ultrasound device can non-invasively enhance homogenous tumor targeting and SDT toxicity of EXO-DVDMS, and the developed endogenous nano-sonosensitizer is a promising nanoplatform for activated cancer theranostics.