A case of CSF1R-related leukoencephalopathy: serial neuroimaging and neuropsychological tests.

Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is one of the most common causes of adult-onset leukodystrophy and is caused by mutation of the CSF1R gene. Brain magnetic resonance imaging (MRI) findings in asymptomatic patients have not been well recognized. We report on the case of a patient with CSF1R-related leukoencephalopathy who had a novel missense variant of the CSF1R gene with a family history of early onset dementia. This is a representative case of CSF1R-related leukoencephalopathy, which shows the progression of brain MRI and cognitive decline from an asymptomatic state.

Detection of association between periodontitis and polymorphisms of IL-1ß + 3954 and TNF-α -863 in the Korean population after controlling for confounding risk factors.

BACKGROUND AND OBJECTIVE: Interleukin (IL)-1 and tumor necrosis factor (TNF)-α are inflammatory cytokines that play an important role in periodontitis, and their genetic variations have been suggested to be associated with increased risk of periodontitis. Focusing on three single nucleotide polymorphisms (SNPs) of IL-1α + 4845, IL-1ß + 3954, and TNF-α -863, we aimed to investigate the relationship between periodontitis risk and the polymorphisms of IL-1 α/ß and TNF-α in Koreans. MATERIAL AND METHODS: Mouthwash samples from 548 subjects (135 controls without periodontitis, 387 generalized chronic periodontitis patients, and 26 generalized aggressive periodontitis patients) were collected for isolation of genomic DNA. Genotyping of selected SNPs was performed using real-time PCR. Univariable associations between the polymorphisms and periodontitis were assessed by chi-squared test or Fisher's exact test. To evaluate the association after controlling for confounding effects of various risk factors, we stratified the subjects according to the presence or absence of self-reported diseases and employed multiple logistic regression model to adjust for age, smoking status, and oral hygiene indices and behaviors. RESULTS: Significant association of IL-1ß + 3954 and TNF-α -863 polymorphisms with periodontitis was observed after adjusting for the confounding risk factors, but not in univariable association analysis. The significant association between genotype CT of IL-1ß + 3954 and increased risk of advanced periodontitis was consistently detected regardless of the status of self-reported diseases. In the polymorphism of TNF-α -863, the genotype with minor allele (CA + AA) was significantly associated with periodontitis susceptibility, which was observed only in the subjects with self-reported diseases. CONCLUSION: The results suggest that genetic variations of IL-1ß + 3954 and TNF-α -863 are associated with increased risk of periodontitis in Koreans. In addition, our findings underscore the importance of controlling for confounding risk factors to detect significant association between genetic factors and risk of periodontitis. A further well-designed large-scale study is needed to warrant our results.

Anti-aquaporin-4 antibody-positive dorsal midbrain syndrome.

Neuromyelitis optica spectrum disorders (NMOSD) can cause various ocular motor disorders in addition to optic neuritis. Ocular motor findings associated with NMOSD include spontaneous vertical and gaze-evoked nystagmus, wall-eyed bilateral internuclear ophthalmoplegia, and trochlear nerve palsy. The association between dorsal midbrain syndrome and anti-aquaporin-4 antibody seropositivity has not been reported. Here, we report a patient displaying typical dorsal midbrain syndrome and anti-aquaporin-4 antibody seropositivity.

Invasion of oral and aortic tissues by oral spirochete Treponema denticola in ApoE(-/-) mice causally links periodontal disease and atherosclerosis.

Treponema denticola is a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between periodontal disease induced by chronic oral T. denticola infection and atherosclerosis in hyperlipidemic ApoE(-/-) mice. ApoE(-/-) mice (n = 24) were orally infected with T. denticola ATCC 35404 and were euthanized after 12 and 24 weeks. T. denticola genomic DNA was detected in oral plaque samples, indicating colonization of the oral cavity. Infection elicited significantly (P = 0.0172) higher IgG antibody levels and enhanced intrabony defects than sham infection. T. denticola-infected mice had higher levels of horizontal alveolar bone resorption than sham-infected mice and an associated significant increase in aortic plaque area (P ≤ 0.05). Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO) levels and increased serum-oxidized low-density lipoprotein (LDL) levels compared to those of sham-infected mice. T. denticola infection altered the expression of genes known to be involved in atherosclerotic development, including the leukocyte/endothelial cell adhesion gene (Thbs4), the connective tissue growth factor gene (Ctgf), and the selectin-E gene (Sele). Fluorescent in situ hybridization (FISH) revealed T. denticola clusters in both gingival and aortic tissue of infected mice. This is the first study examining the potential causative role of chronic T. denticola periodontal infection and vascular atherosclerosis in vivo in hyperlipidemic ApoE(-/-) mice. T. denticola is closely associated with periodontal disease and the rapid progression of atheroma in ApoE(-/-) mice. These studies confirm a causal link for active oral T. denticola infection with both atheroma and periodontal disease.

Prosthecobacter algae sp. nov., isolated from activated sludge using algal metabolites.

A Gram-stain-negative, fusiform-shaped, facultatively anaerobic bacterial strain, designated EBTL04(T), was isolated from activated sludge using algal metabolites and taxonomically characterized through polyphasic investigation. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain EBTL04(T) belongs to the family Verrucomicrobiaceae, class Verrucomicrobiae, and is closely related to Prosthecobacter dejongeii DSM 12251(T) (98.6 % sequence similarity), Prosthecobacter fusiformis ATCC 25309(T) (97.9 %), Prosthecobacter debontii DSM 14044(T) (97.5%), Prosthecobacter vanneervenii DSM 12252(T) (94.7%) and Prosthecobacter fluviatilis KCTC 22182(T) (93.7%). The G+C content of the genomic DNA of strain EBTL04(T) was 62.7 mol%. The menaquinone MK-6 was detected as the predominant quinone. Strain EBTL04(T) contained phosphatidylethanolamine, phosphatidylglycerol and phosphatidylserine as major polar lipids. A fatty acid profile with C(16 : 1)ω5c, iso-C(14 : 0), C(16 : 0), anteiso-C(15 : 0) and C(14 : 0) as the major components supported the classification of strain EBTL04(T) in the genus Prosthecobacter. Based on several phenotypic, genotypic and chemotaxonomic features, strain EBTL04(T) was clearly differentiated from its phylogenetic neighbours. Therefore, strain EBTL04(T) should be considered to represent a novel species of the genus Prosthecobacter, for which the name Prosthecobacter algae sp. nov. is proposed. The type strain is EBTL04(T) ( = KCTC 23681(T) = JCM 18053(T)).

The Usefulness of 18F-FDG PET to Differentiate Subtypes of Dementia: The Systematic Review and Meta-Analysis.

Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: 18F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

Luteolibacter yonseiensis sp. nov., isolated from activated sludge using algal metabolites.

A Gram-negative, rod-shaped, aerobic bacterial strain, designated EBTL01(T), was isolated from activated sludge by using metabolites of microalgae Ankistrodesmus gracilis SAG278-2. Phylogenetic analyses based on 16S rRNA gene sequence showed that strain EBTL01(T) belongs to the family Verrucomicrobiaceae, class Verrucomicrobiae, and is related most closely to Luteolibacter pohnpeiensis A4T-83(T) (95.5 % sequence similarity) and Luteolibacter algae A5J-41-2(T) (95.2 %). The G+C content of the genomic DNA of strain EBTL01(T) was 56.3 mol% and the menaquinone MK-9 was detected as the predominant quinone. Major fatty acid components were iso-C14 : 0, C16 : 1ω7c and C16 : 0. The amino acids of the cell-wall peptidoglycan contained muramic acid and meso-diaminopimelic acid. These profile results supported the affiliation of strain EBTL01(T) to the genus Luteolibacter. On the other hand, based on chemotaxonomic properties and phenotypic characteristics, strain EBTL01(T) could be clearly differentiated from its phylogenetic neighbours. Therefore, strain EBTL01(T) represents a novel species of the genus Luteolibacter, for which the name Luteolibacter yonseiensis sp. nov. is proposed. The type strain is EBTL01(T) ( = KCTC 23678(T) = JCM 18052(T)).

MIPs are ancestral ligands for the sex peptide receptor.

Upon mating, females of many animal species undergo dramatic changes in their behavior. In Drosophila melanogaster, postmating behaviors are triggered by sex peptide (SP), which is produced in the male seminal fluid and transferred to female during copulation. SP modulates female behaviors via sex peptide receptor (SPR) located in a small subset of internal sensory neurons that innervate the female uterus and project to the CNS. Although required for postmating responses only in these female sensory neurons, SPR is expressed broadly in the CNS of both sexes. Moreover, SPR is also encoded in the genomes of insects that lack obvious SP orthologs. These observations suggest that SPR may have additional ligands and functions. Here, we identify myoinhibitory peptides (MIPs) as a second family of SPR ligands that is conserved across a wide range of invertebrate species. MIPs are potent agonists for Drosophila, Aedes, and Aplysia SPRs in vitro, yet are unable to trigger postmating responses in vivo. In contrast to SP, MIPs are not produced in male reproductive organs, and are not required for postmating behaviors in Drosophila females. We conclude that MIPs are evolutionarily conserved ligands for SPR, which are likely to mediate functions other than the regulation of female reproductive behaviors.

Effects of a simplified drilling protocol at 50 rpm on heat generation under water-free conditions: an in vitro study.

PURPOSE: In recent years, guided implant surgery has been widely used for the convenience of patients and surgeons. Further streamlining the surgical procedure would make implant surgery more convenient. Low-speed water-free conditions are often used in guided implant surgery. Therefore, in this study, we attempted to confirm once again whether drilling was safe at a low speed without water. The main purpose of this study was to evaluate whether a simplified drilling protocol that omits some intermediate steps in the drilling process was safe from the viewpoint of heat generation. METHODS: D1 density artificial bone blocks were drilled under 50 rpm, 10 N·cm water-free conditions, and the surface temperature was measured using a digital infrared camera. First, drilling was performed with the sequential drilling method, which is the most widely used technique. Second, for each drill diameter, the temperature change was measured while performing simplified drilling with omission of the previous 1, 2, or 3 steps. RESULTS: In sequential drilling, the heat generated during drilling at all diameters was less than the critical temperature of osteonecrosis (47°C) except for the ⌀2 drill. Statistical significance was observed in all groups when comparing sequential and simplified drilling in the ⌀3.2, ⌀3.8, and ⌀4.3 drills (P<0.001). However, in the simplified drilling procedures, the temperature was below the osteonecrosis threshold temperature (47°C) except for the ⌀4.3 drill with the omission of the previous 3 steps (⌀3.0, ⌀3.2, and ⌀3.8). CONCLUSIONS: In general, drilling under low-speed, water-free conditions has shown stable results in terms of heat generation. Simplified drilling showed statistically significantly greater heat generation than sequential drilling. However, most of the diameters and omitted steps seem to be clinically acceptable, so it will be useful if an appropriate selection is made according to the patient's clinical condition.

Microbial profiling of peri-implantitis compared to the periodontal microbiota in health and disease using 16S rRNA sequencing.

PURPOSE: The objective of this study was to analyze the microbial profile of individuals with peri-implantitis (PI) compared to those of periodontally healthy (PH) subjects and periodontitis (PT) subjects using Illumina sequencing. METHODS: Buccal, supragingival, and subgingival plaque samples were collected from 109 subjects (PH: 30, PT: 49, and PI: 30). The V3-V4 region of 16S rRNA was sequenced and analyzed to profile the plaque microbiota. RESULTS: Microbial community diversity in the PI group was higher than in the other groups, and the 3 groups showed significantly separated clusters in the buccal samples. The PI group showed different patterns of relative abundance from those in the PH and PT groups depending on the sampling site at both genus and phylum levels. In all samples, some bacterial species presented considerably higher relative abundances in the PI group than in the PH and PT groups, including Anaerotignum lactatifermentans, Bacteroides vulgatus, Faecalibacterium prausnitzii, Olsenella uli, Parasutterella excrementihominis, Prevotella buccae, Pseudoramibacter alactolyticus, Treponema parvum, and Slackia exigua. Network analysis identified that several well-known periodontal pathogens and newly recognized bacteria were closely correlated with each other. CONCLUSIONS: The composition of the microbiota was considerably different in PI subjects compared to PH and PT subjects, and these results could shed light on the mechanisms involved in the development of PI.

Retrospective analysis of the effects of non-communicable diseases on periodontitis treatment outcomes.

PURPOSE: We retrospectively analysed patients' dental and periodontal status according to the presence of non-communicable diseases (NCDs) and the effects of NCDs on periodontal treatment outcomes. Factors influencing disease recurrence were investigated using decision tree analysis. METHODS: We analysed the records of patients who visited the Department of Periodontology, Pusan National University Dental Hospital from June 2014 to October 2019. As baseline subjects, 1,362 patients with periodontitis and who underwent full-mouth periodontal examinations before periodontal treatment were selected. Among them, 321 patients who underwent periodontal examinations after the completion of periodontal treatment and 143 who continued to participate in regular maintenance were followed-up. RESULTS: Forty-three percent of patients had a NCD. Patients without NCDs had more residual teeth and lower sum of the number of total decayed, missing, filled teeths (DMFT) scores. There was no difference in periodontal status according to NCD status. Patients with a NCD showed significant changes in the plaque index after periodontal treatment. The decision tree model analysis demonstrated that osteoporosis affected the recurrence of periodontitis. CONCLUSIONS: The number of residual teeth and DMFT index differed according to the presence of NCDs. Patients with osteoporosis require particular attention to prevent periodontitis recurrence.

Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes.

Importance: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. Objective: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. Design, Setting, and Participants: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Main Outcomes and Measures: Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid ß deposition (Aß). Results: A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P < .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aß deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. Conclusions and Relevance: In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.

Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity.

Although a range of biological and pharmacological activities of melatonin have been reported, little is known about its potential anti-inflammatory efficacy in periodontal disease. In this study, we investigated the effects of melatonin on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory reactions in the periodontium, and sought to determine the underlying mechanisms of action. Melatonin suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. P. intermedia LPS-induced NF-κB-dependent luciferase activity was significantly inhibited by melatonin. Melatonin did not reduce NF-κB transcriptional activity at the level of IκB-α degradation. Melatonin blocked NF-κB signaling through the inhibition of nuclear translocation and DNA-binding activity of NF-κB p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that melatonin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease.

Prevalence and abundance of 9 periodontal pathogens in the saliva of periodontally healthy adults and patients undergoing supportive periodontal therapy.

PURPOSE: This study aimed to examine the prevalence and abundance of 9 representative periodontal pathogens in the saliva samples of periodontally healthy subjects (PH) and patients with periodontitis who underwent supportive periodontal therapy (SPT). The age-specific distribution of these pathogens in periodontally healthy individuals was also analyzed. METHODS: One hundred subjects (aged >35 years) were recruited (50 each in the PH and SPT groups) between August 2016 and April 2019. The prevalence and abundance of periodontal pathogens in the PH group were compared with those in periodontally healthy young subjects (94 subjects; aged <35 years), who were included in our previous study. DNA copy numbers of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Campylobacter rectus (Cr), Peptostreptococcus anaerobius (Pa), and Eikenella corrodens (Ec) were analyzed using real-time polymerase chain reaction. RESULTS: The detection frequencies of all pathogens, except Aa, were high in the PH and SPT groups. The ranking order of pathogen DNA copy numbers was similar in both groups. In both groups, Fn had the highest abundance, Aa had the lowest abundance. Additionally, Td was significantly more abundant in men than in women in both groups (P<0.05). Compared with the PH group, the SPT group exhibited significantly lower total bacteria and Fn abundance and higher Pg abundance (P<0.05). The age-specific pathogen distribution analysis revealed a significantly low Aa abundance and high Tf and Cr abundance in the PH group. CONCLUSIONS: The clinical parameters and microbial profiles were similar between the SPT and PH groups. However, patients with periodontitis require supportive care to prevent recurrence. As the abundance of some bacteria varied with age, future studies must elucidate the correlation between age-related physiological changes and periodontal bacterial composition.

Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population.

BACKGROUND: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid ß (Aß) positivity using a large sample of Korean population. METHODS: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aß positivity (measured by amyloid positron emission tomography). Aß prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. RESULTS: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aß positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aß positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10-8). Prediction performance for Aß positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. CONCLUSION: The novel genetic variants associated with FGL2 decreased risk of Aß positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.

Home-Visiting Cognitive Intervention for the Community-Dwelling Elderly Living Alone.

BACKGROUND AND PURPOSE: The elderly living alone feel lonelier and more isolated than do those live with others, and they are at higher risk for cognitive decline and depression. This study aimed to assess whether a home-visiting cognitive intervention (HCI) can have positive effects on cognitive improvement for the elderly who living alone. METHODS: HCI was conducted from April 2016 to November 2019. Every elder who lived alone and 2 matched partners met for 8 weeks once a week. The partners visited participants' home and did the HCI which composed of cognitive training and cognitive stimulation activities. The Mini-Mental State Examination-dementia screening (MMSE), Geriatric Depression Scale (GDS), the Korean version of instrumental activities of daily living (K-IADL), and the Social Support Scale (SSS) were evaluated before and after HCI to compare the effect of HCI. RESULTS: A total of 258 participants showed significant improvements in MMSE, GDS, K-IADL, and SSS. The MMSE and GDS scores were significantly improved after HCI in both the normal cognition (NC, n=210) and cognitive impairment (CI, n=48) groups. The cognitive effect of HCI for CI was higher than for NC. Among the NC, the magnitude of cognitive improvement was greater in the higher educated group (above 7 years) than in the other groups. CONCLUSIONS: Active cognitive interventions could provide possible benefits to improve cognition, emotion, and functional abilities. Regular cognitive-care services like HCI are necessary to reduce dementia risk for the elderly who live alone in the community.

Atheroprotective nasal immunization with a heat shock protein 60 peptide from Porphyromonas gingivalis.

PURPOSE: Immunization with Porphyromonas gingivalis heat shock protein 60 (PgHSP60) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSP60 peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. METHODS: Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSP60-derived peptide 14 (Pep14) or peptide 19 (Pep19), or a Western diet and immunization with Pep14 or Pep19 before challenge with Pep14 or Pep19. RESULTS: Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pep14 nasal immunization than in mice that received a Western diet and no Pep14 immunization with or without Pep14 challenge. An immunoblot profile failed to detect serum reactivity to Pep14 in any of the study groups. Stimulation by either Pep14 or Pep19 strongly promoted the induction of CD4+CD25+forkhead box P3 (FoxP3)+ human regulatory T cells (Tregs) in vitro. However, the expression of mouse splenic CD4+CD25+FoxP3+ Tregs was lower in the Pep14-immunized mice than in the Pep14-challenged or Pep19-immunized mice. Levels of serum interferon gamma (IFN-γ) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pep14-immunized mice than in the other groups. Induction of CD25- IL-17+ T helper 17 (Th17) cells was attenuated in the Pep14-immunized mice. CONCLUSIONS: Nasal immunization with Pep14 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-γ and/or suppressing Th17-mediated immunity.

Identification of Potential Oral Microbial Biomarkers for the Diagnosis of Periodontitis.

Periodontitis is a chronic and multifactorial inflammatory disease that can lead to tooth loss. At present, the diagnosis for periodontitis is primarily based on clinical examination and radiographic parameters. Detecting the periodontal pathogens at the subgingival plaque requires skilled professionals to collect samples. Periodontal pathogens are also detected on various mucous membranes in patients with periodontitis. In this study, we characterized the oral microbiome profiles from buccal mucosa and supragingival space in a total of 272 healthy subjects as a control group, and periodontitis patients as a disease group. We identified 13 phyla, 193 genera, and 527 species and determined periodontitis-associated taxa. Porphyromonas gingivalis, Tannerella forsythia, Treponema denticolar, Filifactor alocis, Porphyromonas endodontalis, Fretibacterium fastiosum and Peptostreptococcus species were significantly increased in both the buccal mucosa and the supragingival space in periodontitis patients. The identified eight periodontitis-associated bacterial species were clinically validated in an independent cohort. We generated the prediction model based on the oral microbiome profiles using five machine learning algorithms, and validated its capability in predicting the status of patients with periodontitis. The results showed that the oral microbiome profiles from buccal mucosa and supragingival space can represent the microbial composition of subgingival plaque and further be utilized to identify potential microbial biomarkers for the diagnosis of periodontitis. Besides, bacterial community interaction network analysis found distinct patterns associated with dysbiosis in periodontitis. In summary, we have identified oral bacterial species from buccal and supragingival sites which can predict subgingival bacterial composition and can be used for early diagnosis of periodontitis. Therefore, our study provides an important basis for developing easy and noninvasive methods to diagnose and monitor periodontitis.

Assessing the effects of cyclosporine A on the osteoblastogenesis, osteoclastogenesis, and angiogenesis mediated by human periodontal ligament stem cells.

BACKGROUND: This study was performed to investigate the effects of cyclosporine A (CsA) on the osteogenic differentiation, osteoclastogenic-supporting ability, and angiogenic potential of human periodontal ligament stem cells (hPDLSCs). METHODS: hPDLSCs were isolated from the extracted teeth of orthodontic patients. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red (ARS) staining. Real-time polymerase chain reaction (PCR) was used to quantify transcripts. Tartrate-resistant acid phosphatase staining of bone marrow-derived macrophages (BMMs) and tube formation assays on human umbilical vein endothelial cells (HUVECs) were performed after treating cells with the conditioned media from CsA-exposed or non-exposed hPDLSCs. Signaling pathways mediating the angiogenic activity were investigated using western blotting. RESULTS: CsA suppressed the proliferation of hPDLSCs but enhanced osteogenic differentiation as determined by ALP and ARS staining and PCR of osteogenic transcripts. The expressions of osteoclastogenic transcripts in hPDLSCs and the differentiation of BMMs treated with conditioned medium from CsA-exposed hPDLSCs were unaffected by CsA. However, the expressions of angiogenic transcripts and the transcripts known to support angiogenesis-phosphorylation of extracellular signal p-regulated kinase (ERK) and p38, and c-fos-were inhibited. Conditioned medium from CsA-exposed hPDLSCs suppressed the tube forming abilities of HUVECs. CONCLUSIONS: CsA enhanced the osteogenic differentiation and reduced angiogenesis by blocking the ERK and p38/c-fos pathway in hPDLSCs. It is necessary to confirm whether this phenomenon is also observed in vivo in subsequent animal experiments.

Prediction of Chronic Periodontitis Severity Using Machine Learning Models Based On Salivary Bacterial Copy Number.

Periodontitis is a widespread chronic inflammatory disease caused by interactions between periodontal bacteria and homeostasis in the host. We aimed to investigate the performance and reliability of machine learning models in predicting the severity of chronic periodontitis. Mouthwash samples from 692 subjects (144 healthy controls and 548 generalized chronic periodontitis patients) were collected, the genomic DNA was isolated, and the copy numbers of nine pathogens were measured using multiplex qPCR. The nine pathogens are as follows: Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Campylobacter rectus (Cr), Aggregatibacter actinomycetemcomitans (Aa), Peptostreptococcus anaerobius (Pa), and Eikenella corrodens (Ec). By adding the species one by one in order of high accuracy to find the optimal combination of input features, we developed an algorithm that predicts the severity of periodontitis using four machine learning techniques. The accuracy was the highest when the models classified "healthy" and "moderate or severe" periodontitis (H vs. M-S, average accuracy of four models: 0.93, AUC = 0.96, sensitivity of 0.96, specificity of 0.81, and diagnostic odds ratio = 112.75). One or two red complex pathogens were used in three models to distinguish slight chronic periodontitis patients from healthy controls (average accuracy of 0.78, AUC = 0.82, sensitivity of 0.71, and specificity of 0.84, diagnostic odds ratio = 12.85). Although the overall accuracy was slightly reduced, the models showed reliability in predicting the severity of chronic periodontitis from 45 newly obtained samples. Our results suggest that a well-designed combination of salivary bacteria can be used as a biomarker for classifying between a periodontally healthy group and a chronic periodontitis group.