Differential Mechanism of Periodontitis Progression in Postmenopause.
Ontology highlight
ABSTRACT:
SUBMITTER: Lee DJ
PROVIDER: S-EPMC6113945 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Context:The Early vs Late Intervention Trial with Estradiol showed that hormone therapy (HT) reduced progression of atherosclerosis when initiated in early but not in late postmenopause. Objective:This posttrial analysis examined the association between plasma estradiol (E2) levels and atherosclerosis determined by rate of change in carotid artery intima-media thickness (CIMT) and tested whether this association is equally evident in early (<6 years) vs late (?10 years) postmenopause. Design:Randomized controlled trial stratified by time since menopause (ClinicalTrials.gov no. NCT00114517). Mixed-effects linear models tested the association of E2 levels with CIMT rate of change. Setting:Los Angeles, California. Participants:Healthy women in postmenopause. Intervention:Oral E2 with/without cyclic vaginal progesterone. Main Outcome Measures:Plasma E2 levels and CIMT assessed every 6 months over an average of 4.8 years. Results:Among 596 women in postmenopause, higher E2 level was inversely associated with CIMT progression in those in early postmenopause (P = 0.041) and positively associated with CIMT progression in those in late postmenopause (P = 0.006) (P for interaction <0.001). CIMT progression rates for the lowest vs highest quartile of E2 levels among women in early postmenopause were 8.5 and 7.2 ?m/y, respectively , whereas among women in late postmenopause they were 9.8 and 11.7 ?m/y, respectively. Conclusion:E2 levels were differentially associated with atherosclerosis progression according to timing of HT initiation. With higher E2 levels, CIMT progression rate was decreased among women in early postmenopause but increased among women in late postmenopause. These results support the timing hypothesis of HT initiation on cardiovascular benefit, with reduced atherosclerosis progression for initiation during early postmenopause.
| S-EPMC6300071 | biostudies-literature
Project description:Periodontitis and diabetes mellitus (DM) have a bidirectional relationship. Periodontitis is initiated by dysbiosis of oral microorganisms, and in particular, the characteristics of the microorganisms that have penetrated the tissue are directly related to the disease; therefore, we investigated the effect of DM on intragingival microbial profiling of patients with periodontitis. A total of 39 subjects were recruited and divided into three groups in this case control study as follows: healthy (NA, 10), periodontitis only (PD, 18), and periodontitis with DM (PD_DM, 11). Gingival tissue was collected, DNA was extracted, and whole-genome sequencing was performed. PD and PD_DM showed different characteristics from NA in diversity and composition of the microbial community; however, no difference was found between the PD nad PD_DM. PD_DM showed discriminatory characteristics for PD in the network analysis. PD showed a network structure in which six species were connected, including three red complex species, and PD_DM's network was more closely connected and expanded, with six additional species added to the PD network. Although DM did not significantly affect α- and β-diversity or abundance of phyla and genera of microbiota that invaded the gingival tissue of patients with periodontitis, DM will affect the progression of periodontitis by strengthening the bacterial network in the gingival tissue.
| S-EPMC9755495 | biostudies-literature
Project description:Periodontitis is characterized by irreversible destruction of periodontal tissue. At present, the accepted etiology of periodontitis is based on a three-factor theory including pathogenic bacteria, host factors, and acquired factors. Periodontitis development usually takes a decade or longer and is therefore called chronic periodontitis (CP). To search for genetic factors associated with CP, several genome-wide association study (GWAS) analyses were conducted; however, polymorphisms associated with CP have not been identified. Epigenetics, on the other hand, involves acquired transcriptional regulatory mechanisms due to reversibly altered chromatin accessibility. Epigenetic status is a condition specific to each tissue and cell, mostly determined by the responses of host cells to stimulations by local factors, like bacterial inflammation, and systemic factors such as nutrition status, metabolic diseases, and health conditions. Significantly, epigenetic status has been linked with the onset and progression of several acquired diseases. Thus, epigenetic factors in periodontal tissues are attractive targets for periodontitis diagnosis and treatments. In this review, we introduce accumulating evidence to reveal the epigenetic background effects related to periodontitis caused by genetic factors, systemic diseases, and local environmental factors, such as smoking, and clarify the underlying mechanisms by which epigenetic alteration influences the susceptibility of periodontitis.
| S-EPMC9218144 | biostudies-literature
Project description:BackgroundPeriodontitis has emerged as a potential risk factor for chronic obstructive pulmonary disease (COPD). However, the precise mechanism through which periodontitis influences the progression of COPD requires further investigation. Ferroptosis is one of the crucial pathogenesis of COPD and recent researches suggested that periodontitis was associated with ferroptosis. Nonetheless, the relationship among periodontitis, COPD and ferroptosis remains unclear. This study aimed to elucidate whether periodontitis contributes to COPD exacerbation and to assess the potential impact of ferroptosis on periodontitis affecting COPD.MethodsThe severity of COPD was assessed using Hematoxylin and eosin (H&E) staining and lung function tests. Iron assays, malondialdehyde (MDA) measurement and RT-qPCR were used to investigate the potential involvement of ferroptosis in the impact of periodontitis on COPD. Co-cultures of periodontitis associated pathogen Phophyromonas gingivalis (P. gingivalis) and lung tissue cells were used to evaluate the effect of P. gingivalis on inducing the ferroptosis of lung tissue via RT-qPCR analysis. Clinical Bronchoalveolar Lavage Fluid (BALF) samples from COPD patients were collected to further validate the role of ferroptosis in periodontal pathogen-associated COPD.ResultsPeriodontitis aggravated the COPD progression and the promotion was prolonged over time. For the first time, we demonstrated that periodontitis promoted the ferroptosis-associated iron accumulation, MDA contents and gene expressions in the COPD lung with a time-dependent manner. Moreover, periodontitis-associated pathogen P. gingivalis could promote the ferroptosis-associated gene expression in single lung tissue cell suspensions. Clinical BALF sample detection further indicated that ferroptosis played essential roles in the periodontal pathogen-associated COPD.ConclusionPeriodontitis could contribute to the exacerbation of COPD through up-regulating the ferroptosis in the lung tissue.
| S-EPMC10500905 | biostudies-literature
Project description:Around 14.5 million peri- and postmenopausal women currently live in Germany. Moreover, approximately 450 000 women, each with a life expectancy of around 85 years, reach menopause every year in Germany. The challenge is therefore to find a therapy with few side effects which could improve the quality of life of women with menopausal symptoms. The aim of hormone therapy (HT) is to remedy hormone deficiencies using substances that offer the best trade-off between benefits and risks. This is where progesterone has a new and important role to play. Progesterone is one of the most important gestagens. Biologically effective progesterone formulations created with micronization techniques have been used in clinical practice since 1996. Nevertheless, up until 2003 preference was given to synthetic gestagens rather than progesterone. The increased breast cancer hazard ratio of 1.23 reported in the WHI study and of 2 given in the Million Women Study has been associated with the use of synthetic gestagens. In a comparison between synthetic gestagens and progesterone, the E3N Study showed that the transdermal administration of estrogen and progesterone did not lead to an increase in breast cancer rates (RR: 1.08). The administration of progesterone does not change the HDL/LDL cholesterol ratio. Because of its anti-mineralocorticoid effect, progesterone has no impact on carbohydrate metabolism, hemostasis, blood pressure, thrombogenicity and body weight. The administration of 200 mg/day progesterone over 12 days of a menstrual cycle or a daily administration of 100 mg combined with an estrogen are a safe and well-tolerated option to treat menopausal symptoms, with a better benefit risk profile compared to synthetic gestagens.
| S-EPMC4245250 | biostudies-literature
Project description:The present study investigated the role of the nitric oxide (NO) signaling pathway in the progression of periodontal disease, and explored the related genetic mechanisms. An experimental model of periodontitis was established in Sprague-Dawley rats, then they were divided into normal control, and 2, 4 and 6 weeks post-surgery groups. NO content was determined in the saliva of rats from each group by the Griess reagent method. Pathological changes of the periodontal tissue sections were evaluated with hematoxylin-eosin staining. The periodontal tissue sections were also evaluated by immunohistochemistry to detect the expression of inducible nitric oxide synthase 2 (iNOS2). Significant differences were detected in the iNOS2 expression of the periodontal tissue based on immunohistochemistry. There was a significant time-dependent increase in NO serum levels post-surgery. Two single nucleotide polymorphisms (SNP), rs2297518 in the iNOS gene and rs841 of the GTP cyclohydrolase I gene, were identified to be closely related to alveolar bone resorption, which is associated with the SNP rs1049255 of the cytochrome b-245 ? chain gene. The present findings demonstrated that iNOS2 values increased and NO levels increased with the progression of periodontitis. These results are in agreement with the previous literature. It was hypothesized that NO has a role in the occurrence and development of periodontal disease by regulating the action of certain cytokines.
| S-EPMC6796435 | biostudies-literature
Project description:The oral microbiome is one of the most complex microbial communities in the human body, and due to circumstances not completely understood, the healthy microbial community becomes dysbiotic, giving rise to periodontitis, a polymicrobial inflammatory disease. We previously reported the results of community-wide gene expression changes in the oral microbiome during periodontitis progression and identified signatures associated with increasing severity of the disease. Small noncoding RNAs (sRNAs) are key players in posttranscriptional regulation, especially in fast-changing environments such as the oral cavity. Here, we expanded our analysis to the study of the sRNA metatranscriptome during periodontitis progression on the same samples for which mRNA expression changes were analyzed. We observed differential expression of 12,097 sRNAs, identifying a total of 20 Rfam sRNA families as being overrepresented in progression and 23 at baseline. Gene ontology activities regulated by the differentially expressed (DE) sRNAs included amino acid metabolism, ethanolamine catabolism, signal recognition particle-dependent cotranslational protein targeting to membrane, intron splicing, carbohydrate metabolism, control of plasmid copy number, and response to stress. In integrating patterns of expression of protein coding transcripts and sRNAs, we found that functional activities of genes that correlated positively with profiles of expression of DE sRNAs were involved in pathogenesis, proteolysis, ferrous iron transport, and oligopeptide transport. These findings represent the first integrated sequencing analysis of the community-wide sRNA transcriptome of the oral microbiome during periodontitis progression and show that sRNAs are key regulatory elements of the dysbiotic process leading to disease.
| S-EPMC4561685 | biostudies-literature
Project description:ObjectiveThis study aims to identify the periodontitis factor that activates excessive autophagy in pancreatic β cells, resulting in organic lesions of pancreatic islet tissues and diminished insulin secretion, thereby accelerating the progression of diabetes mellitus (DM).MethodsSprague-Dawley (SD) rats were induced with periodontitis (PD), type 2 diabetes mellitus (T2DM), or the combination of T2DM and PD (DP) through a high-sugar/high-fat diet and ligation of the tooth neck with silk thread. Alveolar bone resorption was assessed using Micro-CT, blood glucose levels were measured with a blood glucose meter, pancreatic tissue pathology was examined through HE staining, and the expression of autophagy-related proteins Beclin1 and LC3II/LC3I was analyzed using Western blotting.ResultsMicro-CT results revealed more pronounced alveolar bone resorption and root bifurcation exposure in the PD and DP groups compared to the control group, with the DP group exhibiting the most severe condition. HE staining demonstrated the formation of periodontal pockets, severe alveolar bone destruction, and abnormal pancreatic islet tissue morphology in the PD and DP groups. The serum levels of IL-6, TNF-α, and IL-1β increased sequentially in the control, DM, PD, and DP groups (P < 0.05). Relative expressions of GCK and GLUT-2 mRNA decreased in the PD group compared to the control group (P > 0.05), while the mRNA expressions in the DP and DM groups increased (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Western blot results indicated increased expression levels of autophagy proteins Beclin1 and LC3II/LC3I in the DM and DP groups compared to the control group (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05).ConclusionThe findings demonstrate that periodontal inflammatory factors may promote the enhancement of pancreatic cell autophagy in diabetic rats.
| S-EPMC10823111 | biostudies-literature
Project description:BackgroundHost immunity plays an important role against oral microorganisms in periodontitis.MethodsThis study assessed the infiltrating immune cell subtypes in 133 healthy periodontal and 210 chronic periodontitis tissues from Gene Expression Omnibus (GEO) datasets using the CIBERSORT gene signature files.ResultsPlasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues, when compared to those in healthy controls. In contrast, memory B cells, resting dendritic, mast cells and CD4 memory cells, as well as activated mast cells, M1 and M2 macrophages, and follicular helper T cells, were mainly present in healthy periodontal tissues. Furthermore, these periodontitis tissues generally contained a higher proportion of activated CD4 memory T cells, while the other subtypes of T cells, including resting CD4 memory T cells, CD8 T cells, follicular helper T cells (TFH) and regulatory T cells (Tregs), were relatively lower in periodontitis tissues, when compared to healthy tissues. The ratio of dendritic and mast cells and macrophages was lower in periodontitis tissues, when compared to healthy tissues. In addition, there was a significant negative association of plasma cells with most of the other immune cells, such as plasma cells vs. memory B cells (γ = - 0.84), plasma cells vs. resting dendritic cells (γ = - 0.64), plasma cells vs. resting CD4 memory T cells (γ = 0.50), plasma cells versus activated dendritic cells (γ = - 0.46), plasma cells versus TFH (γ = - 0.46), plasma cells versus macrophage M2 cells (γ = - 0.43), or plasma cells versus macrophage M1 cells (γ = - 0.40), between healthy control and periodontitis tissues.ConclusionPlasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues. The infiltration of different immune cell subtypes in the periodontitis site could lead the host immunity against periodontitis.
| S-EPMC7590666 | biostudies-literature
Project description:PurposeThe aim of this study was to compare microRNA (miRNA) gene expression in saliva using miRNA polymerase chain reaction (PCR) arrays in healthy and aggressive periodontitis (AP) patients.MethodsPCR arrays of 84 miRNAs related to the human inflammatory response and autoimmunity from the saliva samples of 4 patients with AP and 4 healthy controls were performed. The functions and diseases related to the miRNAs were obtained using TAM 2.0. Experimentally validated targets of differentially expressed miRNAs were obtained from mirTarBase. Gene ontology terms and pathways were analyzed using ConsensusPathDB.ResultsFour downregulated miRNAs (hsa-let-7a-5p, hsa-let-7f-5p, hsa-miR-181b-5p, and hsa-miR-23b-3p) were identified in patients with AP. These miRNAs are associated with cell death and innate immunity, and they target genes associated with osteoclast development and function.ConclusionsThis study is the first analysis of miRNAs in the saliva of patients with AP. Identifying discriminatory human salivary miRNA biomarkers reflective of periodontal disease in a non-invasive screening assay is crucial for the development of salivary diagnostics. These data provide a first step towards the discovery of key salivary miRNA biomarkers for AP.
| S-EPMC7606899 | biostudies-literature