Abstract
Aims
Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in ...atherosclerosis and dissect the underlying mechanisms.
Methods and results
A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE−/− mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum-induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum-induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes.
Conclusions
PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum-promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis.
Graphical Abstract
Graphical Abstract
Periodontitis and hypertension often occur as comorbidities, which need to be treated at the same time. To resolve this issue, a controlled‐release composite hydrogel approach is proposed with dual ...antibacterial and anti‐inflammatory activities as a resolution to achieve the goal of co‐treatment of comorbidities. Specifically, chitosan (CS) with inherent antibacterial properties is cross‐linked with antimicrobial peptide (AMP)‐modified polyethylene glycol (PEG) to form a dual antibacterial hydrogel (CS‐PA). Subsequently, curcumin loaded into biodegradable nanoparticles (CNP) are embedded in the hydrogel exhibiting high encapsulation efficiency and sustained release to achieve long‐term anti‐inflammatory activities. In a mouse model of periodontitis complicated with hypertension, CS‐PA/CNP is applied to gingival sulcus and produced an optimal therapeutic effect on periodontitis and hypertension simultaneously. The therapeutic mechanisms are deeply studied and indicated that CS‐PA/CNP exerted excellent immunoregulatory effects by suppressing the accumulation of lymphocytes and myeloid cells and enhanced the antioxidant capacity and thus the anti‐inflammatory capacity of macrophages through the glutathione metabolism pathway. In conclusion, CS‐PA/CNP has demonstrated its superior therapeutic effects and potential clinical translational value in the co‐treatment of periodontitis and hypertension, and also serves as a drug delivery platform to provide combinatorial therapeutic options for periodontitis with complicated pathogenesis.
CS‐PA hydrogel with dual antibacterial activities is fabricated through the thiol‐maleimide click reaction, where curcumin nanoparticles are physically incorporated. By in situ injection of the hydrogel into periodontal pockets, CS‐PA/CNP can inhibit various periodontal pathogens and restore immune hemostasis to effectively manage periodontitis, which reverses periodontitis‐exacerbated hypertension in the meantime.
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease with xerosis, itchiness, as well as interconnection with immunoglobulin E (Ig E), mediated foods including airborne allergies. ...AD is not only related to the diminished stratum corneum barrier but also presents with an unusual expression of tight junctions (TJs) proteins. TJ barrier dysfunction leads to impairment in the stratum corneum (SC) barrier. The significant role of TJs in the epidermal barrier as indicated by Claudin-1 (Cldn-1) deficient mice that undergo high transepidermal water loss (TEWL) and skin dehydration. In atopic dermatitis, downregulation of Cldn-1 was observed due to inflammation. Still, a lack of distinct understanding exists in considering tight junction barrier impairment as a cause or outcome in atopic dermatitis. This review summarizes TJs main role in skin barrier function and TJ proteins (TJPs) expression observed in AD patients.
To compare the applicability and validity of dental age (DA) estimated by Willems method and cervical vertebral bone age (CVBA) evaluated by regression formula in estimating the chronological age of ...children in Shanghai.
Panoramic radiographs and lateral cephalograms were retrospectively collected from 320 subjects (160 males, 160 females), totaling 640 images. Discrepancies between chronological and estimated ages were statistically calculated by paired samples t test or Wilcoxon signed rank test using SPSS 25.0 software package. The accuracy of the two methods was comprehensively evaluated by comparing their standard deviation, mean absolute error (MAE) and the correct rate of acceptable range of estimated age error.
The mean DA underestimated CA by 0.75±1.03 years for males and by 1.05±1.18 years for females; whereas the mean CVBA underestimated CA by 0.78±1.40 years for males and 0.53±1.31 years for females. MAE of Willems method was 1.15 years and the MAE of regression formula of CVBA was 1.20 years. The
Some evidence suggests abnormalities in fatty acids in patients with atopic dermatitis (AD), and benefits of supplementation with these fatty acids have been reported. However, there is still ...substantial controversy on the correlation between fatty acids and AD. Therefore, the aim of this study was to determine whether fatty acid levels are causally related to AD using a Mendelian randomization approach.
We evaluated the data about the fatty acids levels and AD with various methods from Genome-Wide Association Study (GWAS). GWAS results were available both from European ancestry. Mendelian randomization methods were used to analysis the casual inference of fatty acids on AD. MR Egger and MR-PRESSO were used to determine pleiotropy and heterogeneity. Further analysis was conducted using instruments associated with the
genes to address mechanisms involved. We also used Multivariate MR (MVMR) to show the independent casual inference of omega-3 (n-3) fatty acids on AD.
Mendelian randomization (MR) analysis suggests that n-3 fatty acid levels are associated with a lower risk of AD (n-3 OR
: 0.92, 95% confidence interval CI: 0.87-0.98;
= 0.01). Moreover, docosahexaenoic acids (DHA) levels, which is a kind of long-chain, highly unsaturated omega-3 (n-3) fatty acid, and its higher level was associated with a lower risk of AD (DHA ORIVW: 0.91, 95% CI: 0.84-0.98;
= 0.02). We ran multivariable MR analysis while controlling for variables within the other types of fatty acids. The effect estimates agreed with the preliminary MR analysis indicating the effect of n-3 fatty acids levels on AD was robust. MR-egger suggest no significant pleiotropy and heterogeneity on genetic instrumental variants. Outliers-corrected MR analyses after controlling horizontal pleiotropy were still robust. The single-SNP analyses revealed that n-3 fatty acids are likely linked to a decreased risk of AD through
cluster, highlighting the significance of the
gene in the fatty acids synthesis pathway in the development of AD.
Our studies suggest that n-3 fatty acids may reduce the risk of AD. Risk prediction tools based on n-3 fatty acid levels may be valuable methods for improving AD screening and primary prevention. To reduce the risk of AD, individuals could enhance n-3 fatty acids intake through supplement or diet.
Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent ...studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17
γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4
T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.
Abstract
Background
Parkinson’s disease (PD) is a common chronic neurological disorder with a high risk of disability and no cure. Periodontitis is an infectious bacterial disease occurring in ...periodontal supporting tissues. Studies have shown that periodontitis is closely related to PD. However, direct evidence of the effect of periodontitis on PD is lacking. Here, we demonstrated that ligature-induced periodontitis with application of subgingival plaque (LIP-SP) exacerbated motor dysfunction, microglial activation, and dopaminergic neuron loss in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice.
Results
The 16S rRNA gene sequencing revealed that LIP-SP induced oral and gut dysbiosis. Particularly,
Veillonella parvula
(
V. parvula
) and
Streptococcus mutans
(
S. mutans
) from oral ligatures were increased in the fecal samples of MPTP + LIP-SP treated mice. We further demonstrated that
V. parvula
and
S. mutans
played crucial roles in LIP-SP mediated exacerbation of motor dysfunction and neurodegeneration in PD mice.
V. parvula
and
S. mutans
caused microglial activation in the brain, as well as T helper 1 (Th1) cells infiltration in the brain, cervical lymph nodes, ileum and colon in PD mice. Moreover, we observed a protective effect of IFNγ neutralization on dopaminergic neurons in
V. parvula-
and
S. mutans-
treated PD mice.
Conclusions
Our study demonstrates that oral pathogens
V. parvula
and
S. mutans
necessitate the existence of periodontitis to exacerbate motor dysfunction and neurodegeneration in MPTP-induced PD mice. The underlying mechanisms include alterations of oral and gut microbiota, along with immune activation in both brain and peripheral regions.
Melanoma is a malignant tumor of the melanocytes. microRNAs (miRNAs) are emerging as important regulators of cancer-related processes. A thorough understanding of miRNAs in melanoma progression is ...important for developing new therapeutic targets. miRNA expression was detected by quantitative PCR. In vitro, MTT assay, colony formation assay, invasion assay and flow cytometry analysis were performed to test the effect of miR-573 on melanoma cells. The effect of miR-573 in vivo was validated using a murine xenograft model. Using quantitative PCR, we found that the expression levels of miR-573 were lower in melanoma tissues and cell lines compared to normal skin tissues. miR-573 upregulation inhibited melanoma cell proliferation and invasion, and overexpression of melanoma cell adhesion molecule (MCAM) could alleviate the effect of miR-573 on melanoma cells. In vivo, miR-573 overexpression groups showed lower rates of tumor growth compared with the control group. In conclusion, our results demonstrate that the elevated MCAM expression due to miR-573 reduction is essential in melanoma initiation and progression.
The basal theory of Gauss-MRF is expounded and 2-5 order Gauss MRF models are established. Parameters of the 2-5 order Gauss-MRF models for 300 wood samples＇ surface texture are also estimated by ...using LMS. The data analysis shows that： 1） different rexture parameters have a clear scattered distribution, 2） the main direction of texture is the direction represented by the maximum parameter of Gauss-MRF parameters, and 3） for those samples having the same main direction, the finer the texture is, the greater the corresponding parameter is, and the smaller the other parameters are; and the higher the order of Gauss-MRF is, the more clearly the texture is described. On the condition of the second order Gauss MRF model, parameter B1, B2 of tangential texture are smaller than that of radial texture, while B3 and B4 of tangential texture are greater than that of radial texture. According to the value of separated criterion, the parameter of the fifth order Gauss-MRF is used as feature vector for Hamming neural network classification. As a result, the ratio of correctness reaches 88%.
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