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.

Updated Evidence of Association Between Periodontal Disease and Incident Erectile Dysfunction.

INTRODUCTION: The relationship between periodontal disease (PD) and erectile dysfunction (ED) is still conflicting. AIM: To investigate whether a link between PD and ED exists, and if so, the degree to which it is significant. METHODS: The search strategy included using electronic databases and hand searching works published up to June 2018. MEDLINE via PubMed, EMBASE, Proceedings Web of Science, and Current Contents Connect were searched by 2 independent reviewers. Case-control, cohort, or cross-sectional studies including patients with measures of periodontitis and ED were included in the analysis. Quality assessments and sensitivity analysis of selected studies were performed. MAIN OUTCOME MEASURE: The strength of the association between PD and the prevalence of ED was evaluated. RESULTS: 5 case-control studies with 213,076 participants met the eligibility criteria and were included in the meta-analysis. Patients with PD were 2.85-fold more likely to be diagnosed with ED (OR = 2.85, 95% CI = [1.83, 4.46]). Asian men were reported to be 3.07 times more likely to be at greater risk for the prevalence of ED. Moreover, studies with high quality and case-control design showed 2 times higher risk for ED in PD (OR = 2.44, 95% CI = [1.44, 4.14]). However, the present evidence was not robust enough owing to the high heterogeneity and instability in sensitivity analysis. CLINICAL IMPLICATIONS: Patients with PD may have increased risk of ED, suggesting that dental hygiene should be of concern to clinicians when managing patients with ED. STRENGTH & LIMITATIONS: This article includes a large literature search to confirm the evidence that PD increases the occurrence of ED. However, there are several confounders, such as age and the type of ED, that failed to be adjusted and that generate bias and affect the correlation between the incidence of ED and PD. CONCLUSION: This system review and meta-analysis strengthens the evidence that PD might have important clinical implications for risk stratification of ED. Zhou X, Cao F, Lin Z. Updated evidence of association between periodontal disease and incident erectile dysfunction. J Sex Med 2019;16:61-69.

Meta-Analysis on Associations of RGS1 and IL12A Polymorphisms with Celiac Disease Risk.

The pathogenesis of celiac disease (CD) has been related to polymorphisms in the regulator of G-protein signaling 1 (RGS1) and interleukin-12 A (IL12A) genes, but the existing findings are inconsistent. Our aim is to investigate the associations of two single-nucleotide polymorphisms (SNPs) (rs2816316 in RGS1 and rs17810546 in IL12A) with CD risk using meta-analysis. We searched PubMed and Web of Science on RGS1 rs2816316 and IL12A rs17810546 with CD risk. Odds ratio (OR) and 95% confidence interval (CI) of each SNP were estimated. All statistical analyses were performed on Stata 12.0. A total of seven studies were retrieved and analyzed. The available data indicated the minor allele C of rs2816316 was negatively associated with CD (C vs. A: OR = 0.77, 95% CI = 0.74-0.80), and a positive association was found for the minor allele G of rs17810546 (G vs. A: OR = 1.37, 95% CI = 1.31-1.43). The co-dominant model of genotype effect confirmed the significant associations between RGS1 rs2816316/IL12A rs17810546 and CD. No evidence of publication bias was observed. Our meta-analysis supports the associations of RGS1 and IL12A with CD and strongly calls for further studies to better understand the roles of RGS1 and IL12A in the pathogenesis of CD.

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.

Association between early childhood caries and diet quality among Chinese children aged 2-5 years.

Background: Early childhood caries (ECC) is a major oral problem affecting the health and wellbeing of children worldwide. Diet quality is a better predictor of ECC risk than single foods or specific nutrients. The purposes of this study were to assess the associations between ECC and diet quality among 2- to 5-year-old Chinese children. Methods: A total of 150 eligible children were included in this study. The decayed, missing, or filled surface (dmfs) score was recorded for each child by dental examination. All participants were divided into three groups based on their age and dmfs score [the caries-free group, the ECC group, and the severe early childhood caries (S-ECC) group]. Parents were invited to complete a questionnaire on the general characteristics and oral health behaviors of the participants. The information of 24-h dietary intake from each child was captured via a mobile APP. The Chinese diet balance index for preschool children (DBI_C) indicators score, high bound score (HBS), low bound score (LBS), and diet quality distance (DQD) score were calculated to assess the diet quality of study subjects. The associations of ECC with HBS, LBS, DQD score, and DBI_C indicators score were analyzed by Mann-Whitney U test and multivariable logistic regression analysis. Results: In this study, 21, 31, and 98 children were diagnosed with caries-free, ECC, and S-ECC, respectively. Statistical analysis revealed that the risk of ECC and S-ECC were significantly increased with the DQD score (OR = 1.283 and 1.287, respectively), but both were not associated with HBS and LBS (P > 0.05). In the meantime, the risk of ECC and S-ECC were significantly increased with the Grains score (OR = 1.623 and 1.777, respectively), and significantly decreased with the Food diversity score (OR = 0.271 and 0.315, respectively). Moreover, the risk of S-ECC also significantly decreased with the Vegetables score (OR = 0.137). Conclusion: Both ECC and S-ECC were associated with a high degree of dietary imbalance and grains intake as well as a low degree of food diversity among Chinese children aged 2-5 years. In addition, S-ECC was also associated with a low degree of vegetable intake.

Expression Profiling and Cell Type Classification Analysis in Periodontitis Reveal Dysregulation of Multiple lncRNAs in Plasma Cells.

OBJECTIVE: Periodontitis is a chronic inflammatory disease with a downregulated immune response. The mechanisms of the immune response, especially regarding immune-related long non-coding RNAs (lncRNAs), in periodontitis remain unclear. This study aimed to analyze the immune cell landscapes and immune-related transcriptome expression in periodontitis. MATERIALS AND METHODS: The periodontitis-related microarray data set GSE16134 was downloaded from the Gene Expression Omnibus database. Then, the proportions of the infiltrated immune cell subpopulations were evaluated by Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Differentially expressed immune-related genes (DEMGs) and lncRNAs were analyzed by the "limma" package in R software. Co-expression of DEMGs and lncRNAs in immune cell subpopulations was evaluated. Gene set enrichment analysis (GSEA) was performed to identify alterations in immune function through potential pathways. RESULTS: Increased numbers of plasma cells were observed in periodontitis-affected tissues versus those of healthy tissues, while T cells were downregulated. A total of 51 DEMGs were identified, and 12 immune-related signaling pathways were enriched by GSEA, most of which were related to the stimulation and function of B cells and T cells. Only 3 differentially upregulated lncRNAs (FAM30A, GUSBP11, and LINC00525) were screened for the regulation of the immune response. Besides, the level of lncRNAs (FAM30A, GUSBP11, and LINC00525) expression were positively correlated with the fraction of plasma cells in periodontitis. CONCLUSION: The discovery of differentially expressed immune-related transcriptomes in periodontitis lesions helps to explain the regulation of the immune mechanism in the development of periodontitis.

Decreased Hemoglobin Concentration and Iron Metabolism Disorder in Periodontitis: Systematic Review and Meta-Analysis.

Background: Periodontitis is a chronic inflammatory disease with a possible infectious component. Anemia of inflammation (AI) occurring in various chronic diseases alters the hemoglobin (Hb) concentration and iron status. Currently, the association between periodontitis and AI is still controversial. The aim of this study was to assess the alterations of the level of hematological parameters and iron metabolism markers in patients with or without periodontitis. Methods: Electronic databases (MEDLINE, EMBASE, and Cochrane) were searched to identify publications about anemia and periodontitis. Subgroup analyses regarding gender, extent of periodontitis, and sample size were performed using STATA 12.1. Results: Sixteen studies were included in this meta-analysis. Pooled results showed a decrease in Hb [standardized mean difference (SMD) = -0.76, 95% CI = (-1.15, -0.37)], red blood cell [SMD = -0.69, 95% CI = (-1.09, -0.29)], hematocrit [SMD = -1.13, 95% CI = (-1.69, -0.57)], mean corpuscular volume [SMD = -0.16, 95% CI = (-0.32, -0.01)], and mean corpuscular Hb [SMD = -0.16, 95% CI = (-0.28, -0.04)], but upregulation in erythrocyte sedimentation rate [SMD = 0.63, 95% CI = (0.06, 1.19)]. In addition, patients with periodontitis had a higher level of hepcidin [SMD = 0.59, CI = (0.05, 1.12)] and decreased level of transferrin [SMD = -4.6, CI = (-13.1, -3.90)], with high heterogeneity. Conclusion: This meta-analysis indicates that periodontitis decreases Hb concentration and disturbs the balance of iron metabolism, which confirms strength of association between periodontitis and the development tendency of AI, especially for severe periodontitis. More unbiased cohort studies with larger sample sizes are still warranted to make a definitive judgment in the future.

miR-214 promotes periodontal ligament stem cell osteoblastic differentiation by modulating Wnt/ß­catenin signaling.

The canonical Wnt/ß­catenin signaling is important in the differentiation of human mesenchymal stem cells into osteoblasts. Accumulating evidence suggests that the expression of ß­catenin is, in part, regulated by specific microRNAs (miRNAs). The aim of the present study was to investigate the putative roles of miRNAs in osteoblast differentiation. Polymerase chain reaction (PCR) arrays were used to identify miRNAs that were differentially expressed between differentiated and non­differentiated periodontal ligament stem cells (PDLSCs), and reverse transcription­quantitative PCR (RT­qPCR) was used for validation. Since miR­214 was revealed to be significantly downregulated during PDLSC differentiation, its function was further investigated via silencing and overexpression. In addition, osteogenic differentiation of PDLSCs was evaluated at 10 and 21 days following induction, using Alizarin red staining and RT­qPCR analysis for mRNA expression levels of the osteogenic differentiation markers alkaline phosphatase (ALP), osteocalcin and bone sialoprotein. Furthermore, the potential target genes of miR­214 were investigated using a dual­luciferase reporter assay, RT­qPCR and western blot analysis, whereas a TOPflash/FOPflash reporter plasmid system followed by a luciferase assay was used to examine the effects of miR­214 on Wnt/ß­catenin signaling. The present results demonstrated that miR­214 was significantly downregulated during the osteoblastic differentiation of PDLSCs. Notably, its overexpression inhibited PDLSC differentiation, whereas its knockdown promoted PDLSC differentiation, as revealed by alterations in mRNA expression of osteoblast­specific genes and ALP. In addition, miR­214 was demonstrated to directly interact with the 3'­untranslated region of the ß­catenin gene CTNNB1, and suppressed Wnt/ß­catenin signaling through the inhibition of ß­catenin. The results of the present study suggested that miR­214 may participate in the regulation of the Wnt/ß­catenin signaling pathway, and may have potential as a candidate target for the development of preventive or therapeutic agents for the treatment of patients with osteogenic disorders.

[MINI TITANIUM PLATE FOR TREATMENT OF INTRACAPSULAR CONDYLAR FRACTURES].

OBJECTIVE: To investigate the effectiveness of mini titanium plate for the treatment of intracapsular condylar fractures-type A. METHODS: Between March 2013 and July 2015, 22 cases (26 sides) of intracapsular condylar fractures-type A were treated with mini titanium plate through anterior auricular approach. There were 13 males and 9 females, aged from 16 to 32 years (mean, 22.7 years). The disease causes were traffic accident injury in 17 cases, falling injury in 4 cases, and heavy impact injury in 1 case. Five cases had intracapsular condylar fractures-type A only, and the other cases were accompanied with fractures of mandible, maxillary, or other part of jaw. All patients had different degrees of limitation of opening mouth, occlusal disorder, and joint pain, and the maximum opening was 5-16 mm (mean, 8.6 mm). All patients received surgical treatment within 2 to 9 days after injury (mean, 4 days). The clinical dysfunction index (DI) of Helkimo index was used to evaluate the mandibular motor function postoperatively. According to the 4 basic criterion of cure about mandibular condylar fractures by the international consensus conference in 1999, and maximal mouth opening by HE Dongmei et al., the surgical treatment effectiveness was evaluated. RESULTS: All wounds healed at stage I, with no infection or other complications. All 22 cases were followed up 5-8 months (mean, 6 months). At 1 week after operation, the coronal spiral CT and three-dimensional reconstruction showed that contraposition of fractures was good, and the condyles located in the articular fossa. At 6 months after operation, the maximum opening was 33-42 mm (mean, 35.7 mm). After operation, 3 cases showed the mandible deflected to the affected side when opening, and limited lateral motion. According to the DI evaluation method in Helkimo index, there were 7 sides of DI grade 0, 18 sides of DI grade I, and 1 side of DI grade II. Based on surgical treatment effect of intracapsular condylar fractures-type A, occlusion recovery was obtained in 19 cases (86.36%), maximum opening degree of ≥ 35 mm in 20 cases (90.91%), no symptoms of joint injury in 19 cases (86.36%), and no serious postoperative complications in 22 cases (100%); 17 cases (77.27%) were in accordance with the above 4 items. CONCLUSION: Mini titanium plate is one of the most effective approaches to treat intracapsular condylar fractures-type A.

Osteomyelitis of Maxilla in Infantile With Periorbital Cellulitis: A Case Report.

Infantile osteomyelitis (IO) is an uncommon and life-threatening disease that can be misdiagnosed. Early diagnosis and treatment can reduce the incidence of sequel. In this case report, we present a 25-day-old male infant with apparent edema in the entire left periorbital region. Intraorally, the edema occurred in the mucosa of the upper left alveolar region, and 2 draining fistulas with exuded yellow-white pus were present in the left alveolar region. The patient received constant monitoring after admission, and was diagnosed as IO of the maxilla with periorbital cellulitis and sepsis. He also received incision and drainage and anti-inflammatory treatment. After discharge, the patient was followed up for 3 months by phone call, but no recurrence of symptoms was found. Infantile osteomyelitis is rare in clinic. This case report reminds us of the significance of IO and provides some implications on its diagnosis and treatment.