Mature Plaques Research Articles

Regenerative marine waste towards CaCO3 nanoformulation for Alzheimer's therapy

Alzheimer's disorder (AD) is associated with behavioural and cognitive destruction with due respect to the neurological degeneration. Conventional therapeutic approach for treatment of AD using neuroprotective drugs suffered certain limitations such as poor solubility, insufficient bioavailability, adverse side effects at higher dose and ineffective permeability on blood brain barrier (BBB). Development of nanomaterial based drug delivery system helped to overcome these barriers. Hence the present work focused on encapsulating neuroprotective drug citronellyl acetate within CaCO3 nanoparticles to develop neuroprotective CaCO3 nanoformulation (CA@CaCO3 NFs). CaCO3 was derived from marine conch shell waste, while the neuroprotective drug citronellyl acetate was scrutinized by in-silico high throughput screening. In-vitro findings revealed that CA@CaCO3 nanoformulation exhibited enhanced free radical scavenging activity of 92% (IC50 value - 29.27 ± 2.6 μg/ml), AChE inhibition of 95% (IC50 value - 25.6292 ± 1.5 μg/ml) at its maximum dose (100 μg/ml). CA@CaCO3 NFs attenuated the aggregation of β-amyloid peptide (Aβ) and also disaggregated the preformed mature plaques the major risk factor for AD. Overall, the present study reveals that CaCO3 nanoformulations exhibits potent neuroprotective potential when compared to the CaCO3 nanoparticles alone and citronellyl acetate alone due to the sustained drug release and synergistic effect of CaCO3 nanoparticles and citronellyl acetate depicting the fact that CaCO3 can act as promising drug delivery system for treatment of neurodegenerative and CNS related disorders.

Interleukin-10 -1082 G/A polymorphism and its association with early or severe presentation of coronary artery disease: A systematic review and meta-analysis.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082bp (rs1800896) has been associated with reduced in IL-10 production in vitro. Against this background, we tested the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies. Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science databases and stratified into two subgroups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test. A total of 24 studies were included for quantitative synthesis with a cumulative sample of 19,135 (11,143 cases / 7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95% CI 1.02, 1.50), p=0.03; OR 1.32 (95% CI 1.03, 1.69), p=0.03 and OR 1.18 (95% CI 1.02, 1.36), p=0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD subgroup (p=NS). Sensitivity analysis showed consistent results. IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.

The Roles of Coronary Computed Tomography Angiography in Characterizing Coronary Plaque: Screening, Treatment, and Prevention

One of the major risk factors for coronary atherosclerosis is the gradual formation and maturation of coronary atherosclerotic plaque (CAP) [...].

Type 1 diabetes, periodontal health, and a familial history of hyperlipidaemia is associated with oral microbiota in children: a cross-sectional study

BackgroundHyperlipidaemia may play a significant role in the interrelationship between type 1 diabetes (T1D) and periodontal disease. A potential mechanism that links these three aspects together is the oral microbiota. We wanted to determine if there is an association between hyperlipidaemia, periodontal disease, and the oral microbiota of children with T1D, as this has not yet been explored.MethodsIn a post-hoc, cross-sectional study using 16S rRNA gene sequencing, we explored links between oral bacterial diversity and composition of gingival swab samples from 72 children with T1D to periodontal risk factors and hyperlipidaemia status of first-degree relatives. While multiple periodontal risk factors were assessed, we used periodontal pocket depth of 3 mm to characterise periodontal risk. As periodontal pocket depth confounded the analysis of familial history of hyperlipidaemia, a multivariate analyses were performed (i.e., no periodontal risk markers in children with or without a family history of hyperlipidaemia were compared to counterparts who did not have periodontal risk markers) to examine linkages between these factors and diversity and composition of the microbiome.ResultsIn participants with no periodontitis risk, children with a family history of dyslipidemia had different bacterial diversity and composition compared to those without a familar hisitory. In contrast, such differences did not exist in the children with periodontal risk, whether or not they had a family history of hyperlipidaemia. Co-occurrence networks showed that these differences in children with no periodontists risk were linked to the presence of fewer oral microbial networks, but more microbes linked to mature plaque structures. In contrast, children with periodontal risk markers, regardless of family history of hyperlipidaemia, contained co-occurrence networks that were associated with microbes linked to periodontal disease.ConclusionsIn children diagnosed with T1D, our findings support an association between oral microbiota and two different exposure variables: familial history of hyperlipidaemia and periodontal risk factors.

Sphingolipids and Atherosclerosis: The Dual Role of Ceramide and Sphingosine-1-Phosphate.

Sphingolipids are bioactive molecules that play either pro- and anti-atherogenic roles in the formation and maturation of atherosclerotic plaques. Among SLs, ceramide and sphingosine-1-phosphate showed antithetic properties in regulating various molecular mechanisms and have emerged as novel potential targets for regulating the development of atherosclerosis. In particular, maintaining the balance of the so-called ceramide/S1P rheostat is important to prevent the occurrence of endothelial dysfunction, which is the trigger for the entire atherosclerotic process and is strongly associated with increased oxidative stress. In addition, these two sphingolipids, together with many other sphingolipid mediators, are directly involved in the progression of atherogenesis and the formation of atherosclerotic plaques by promoting the oxidation of low-density lipoproteins (LDL) and influencing the vascular smooth muscle cell phenotype. The modulation of ceramide and S1P levels may therefore allow the development of new antioxidant therapies that can prevent or at least impair the onset of atherogenesis, which would ultimately improve the quality of life of patients with coronary artery disease and significantly reduce their mortality.

Fluorescence Spectroscopy Shows Porphyrins Produced by Cultured Oral Bacteria Differ Depending on Composition of Growth Media

Red fluorophores synthesized by oral bacteria are important for fluorescence-based diagnosis and treatment because they are used as markers for bacterially infected tissue, mature plaque, or calculus. A range of porphyrins have been identified as the source of this fluorescence in carious tissue. It is not clear which of these porphyrins are produced by individual oral bacteria or whether this ability depends on other factors. This study examined and compared the fluorescence spectra produced by selected cultured oral bacteria when grown on agars containing different nutrients with spectra for protoporphyrin IX, Zn-protoporphyrin IX, haematoporphyrin, and haematin. Actinomyces israelii (Deutsche Sammlung von Mikroorganismen [DSM], 43320), Actinomyces naeslundii (DSM 43013), Fusobacterium nucleatum (DSM, 20482), Lactobacillus casei (DSM, 20011), Prevotella intermedia (DSM, 20706), Streptococcus mutans (DSM, 20523), Streptococcus oralis (DSM, 20627), Streptococcus salivarius (DSM, 20560) and Streptococcus sobrinus (DSM, 20742) were rehydrated and grown anaerobically on caso, caso blood (containing 5% sheep blood), and caso chlorophyll (containing 5% spinach extract) agar for 3 days at 37°C in the dark. Colonies were harvested, transferred to ethanol, and centrifuged. Fluorescence emission spectra were recorded from the supernatant at 405 nm excitation (Fluorolog 3–22, Jobin Yvon-Spex ISA, Edison, NJ, USA). All Streptococci, L. casei, and F. nucleatum produced red fluorescence when grown on caso and caso chlorophyll agar but not on caso blood agar. A. naeslundii and P. intermedia emitted intense red fluorescence when grown on caso or caso blood agar but not on caso chlorophyll agar. Fluorescence emission spectra of A. naeslundii and P. intermedia grown on caso blood agar correlated exactly with both fluorescence peaks for protoporphyrin-IX at 632 and 701 nm. Most peaks observed could be correlated with at least one of the emission peaks of protoporphyrin IX, Zn-protoporphyrin IX, or haematoporphyrin. Oral bacteria emitted red fluorescence matching known porphyrins, but this depended on nutrients available in the agar.

Whole-brain microscopy reveals distinct temporal and spatial efficacy of anti-Aβ therapies.

Many efforts targeting amyloid-β (Aβ) plaques for the treatment of Alzheimer's Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti-Aβ treatments through high-resolution light-sheet imaging of electrophoretically cleared brains. We assessed the effect on amyloid plaque formation and growth in Thy1-APP/PS1 mice subjected to β-secretase inhibitors, polythiophenes, or anti-Aβ antibodies. Each treatment showed unique spatiotemporal Aβ clearance, with polythiophenes emerging as a potent anti-Aβ compound. Furthermore, aligning with a spatial-transcriptomic atlas revealed transcripts that correlate with the efficacy of each Aβ therapy. As observed in this study, there is a striking dependence of specific treatments on the location and maturity of Aβ plaques. This may also contribute to the clinical trial failures of Aβ-therapies, suggesting that combinatorial regimens may be significantly more effective in clearing amyloid deposition.

Saliva analysis in children with active caries before and after dental treatment

Background: The amount and quality of saliva play important roles in maintaining an intraoral bacterial balance. The quality of saliva is defined by its buffering capacity, viscosity, pH and protein content. The amount of saliva is usually related to the flow rate. Purpose: This study aimed to compare the flow rate, pH, viscosity and buffering capacity of saliva as well as plaque formation in children before and after dental treatment. Methods: Saliva samples were taken from paediatric patients before their treatments and one month after their dental treatments had ended, and these saliva samples were then analysed. For each sample analysis, the GC Saliva-Check Buffer kit (GC Corporation, Tokyo, Japan) was used to evaluate buffering capacity, pH and flow rate, and the GC Saliva-Check Mutans kit (GC Corporation, Tokyo, Japan) was used for the determination of Streptococcus Mutans. GC Tri Plaque ID gel (GC Corporation, Tokyo, Japan) was applied to evaluate plaque maturation. Results: The pre-treatment buffering capacity, pH and viscosity sample values were found to be significantly lower than the post-treatment values (p<0.05). No statistically significant difference was determined in the amount of saliva pre- and post-treatment (p>0.05). When examining plaque maturation, it was determined that all of the post-treatment plaque was pink. Conclusion: This study showed that the pH, viscosity and buffering capacity of saliva had increased significantly post-treatment and that the formation of plaque had decreased in children with active caries after all their dental treatments had been completed.

Changes in clinical periodontal parameters after removal of fixed orthodontic appliances

The placement of orthodontic appliances influences plaque growth and maturation. Significant differences in biofilm formation and periodontal reaction between different bracket types and between bonded teeth compared with control teeth have been reported, however, have reported significant attachment loss during orthodontic treatment.In patients with a history of periodontitis resulting in displaced teeth, possible orthodontic tooth movements include changes in alignment, space redistribution, and intrusion.To see the changes in clinical periodontal parameters after removal of fixed orthodontic appliancesAfter debonding of braket at dental clinic and before final polishing, probing depth (PD), plaque index (PI), gingival index (GI) and bleeding on probing (BOP) were assessed on the first molars and central incisors of both arches.Probing depth decreased in the right maxillary first molar. Plaque index and gingival index also got deceased. Bleeding on Probing reduced significantly.Buccal probing depth returned to < 3 mm in the first month and interproximal depth in the second month. The mean gingival index was 0.5 after 2 months. Bleeding on probing in half of the teeth was negative after the first month and in other half in the second month.

Association between high-sensitivity C-reactive protein, functional disability, and stroke recurrence in patients with acute ischaemic stroke: A mediation analysis.

SummaryBackgroundPost-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence.MethodsPatients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement.FindingsOf the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0–6.0). The median (IQR) level of hsCRP was 1.73 (0.81–4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04–1.18) and disability (aOR, 1.14; 95% CI, 1.08–1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%–27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results.InterpretationStroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes.FundingBeijing Natural Science Foundation, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Municipal Science & Technology Commission.

Structural amyloid plaque polymorphism is associated with distinct lipid accumulations revealed by trapped ion mobility mass spectrometry imaging.

Understanding of Alzheimer's disease (AD) pathophysiology requires molecular assessment of how key pathological factors, specifically amyloid β (Aβ) plaques, influence the surrounding microenvironment. Here, neuronal lipids have been implicated in Aβ plaque pathology, though the lipid microenvironment in direct proximity to Aβ plaques is still not fully resolved. A further challenge is the microenvironmental molecular heterogeneity, across structurally polymorphic Aβ features, such as diffuse, immature, and mature, fibrillary aggregates, whose resolution requires the integration of advanced, multimodal chemical imaging tools. Herein, we used matrix-assisted laser desorption/ionization trapped ion mobility spectrometry time-of-flight based mass spectrometry imaging (MALDI TIMS TOF MSI) in combination with hyperspectral confocal microscopy to probe the lipidomic microenvironment associated with structural polymorphism of Aβ plaques in transgenic Alzheimer's disease mice (tgAPPSWE ). Using on tissue and ex situ validation, TIMS MS/MS facilitated unambiguous identification of isobaric lipid species that showed plaque pathology-associated localizations. Integrated multivariate imaging data analysis revealed multiple, Aβ plaque-enriched lipid patterns for gangliosides (GM), phosphoinositols (PI), phosphoethanolamines (PE), and phosphatidic acids (PA). Conversely, sulfatides (ST), cardiolipins (CL), and polyunsaturated fatty acid (PUFA)-conjugated phosphoserines (PS), and PE were depleted at plaques. Hyperspectral amyloid imaging further delineated the unique distribution of PA and PE species to mature plaque core regions, while PI, LPI, GM2 and GM3lipids localized to immature Aβ aggregates present within the periphery of Aβ plaques. Finally, we followed AD pathology-associated lipid changes over time, identifying plaque- growth and maturation to be characterized by peripheral accumulation of PI (18:0/22:6). Together, these data demonstrate the potential of multimodal imaging approaches to overcome limitations associated with conventional advanced MS imaging applications. This allowed for the differentiation of both distinct lipid components in a complex micro-environment as well as their correlation to disease-relevant amyloid plaque polymorphs. Cover Image for this issue: https://doi.org/10.1111/jnc.15390.

Succession of oral bacterial colonizers on dental implant materials: An in vitro biofilm model

ObjectivesOral bacterial adhesion on dental implant materials has been extensively studied using in vitro systems but has yielded results restricted to in vitro growth patterns due to limitations in species selection, sustained fastidious anaerobe growth, and mixed culture longevity. The aim of this study was to develop an oral bacterial biofilm model consisting of colonizers representative of the oral microbiome exhibiting temporal shifts characteristic of plaque development and maturation in vivo. MethodsStreptococcus oralis, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Veillonella parvula, Fusobacterium nucleatum, and Porphyromonas gingivalis were grown in monoculture prior to combination in mixed culture. Commercially pure titanium (cpTi) and yttria-stabilized zirconia (ZrO2) disks with polished, acid-etched, or sandblasted surfaces were prepared to evaluate oral bacterial adhesion. After 6 h, 1, 3, 7, 14 and 21 days, genomic DNA from planktonic and adherent bacteria was isolated. Quantitative polymerase chain reaction (qPCR) was used to enumerate the amount and proportion of each species. ResultsEarly-colonizing S. oralis and A. actinomycetemcomitans, dominated after 6 h prior to secondary colonization by F. nucleatum and V. parvula in planktonic (1 day) and sessile (3 days) form. A. naeslundii maintained relatively low but stable bacterial counts throughout testing. After 14 days, late-colonizing P. gingivalis became established in mixed culture and persisted, becoming the dominant species after 21 days. The composition of adherent bacteria across all substrates was statistically similar at all timepoints with notable exceptions including lower S. oralis bacterial counts on polished cpTi (3 days). SignificanceWithin the present model’s limitations, multispecies oral bacterial attachment is similar on surface-treated cpTi and ZrO2.

TRAILBLAZER‐ALZ Study: Dynamics of amyloid reduction after donanemab treatment

AbstractBackgroundAccumulation of amyloid‐β (Aβ) peptide in amyloid plaques is a pathological hallmark of Alzheimer’s disease (AD). Reduction of Aβ could slow the progression of AD. Donanemab is an antibody specific for the N‐terminal pyroglutamate Aβ epitope that is only present in mature brain amyloid plaques. In the TRAILBLAZER‐ALZ study, 67.8% (n=61) of donanemab‐treated participants became amyloid negative by 76 weeks. Here we further characterize amyloid reduction after donanemab treatment.MethodParticipants (placebo N=84, donanemab N=69) that completed 4 florbetapir scans in TRAILBLAZER‐ALZ were analyzed for amyloid reduction rate, measured in centiloids (CL). Donanemab dosing was 700mg every 4 weeks (Q4W) for the first 3 doses, then 1400mg Q4W, for up to 76 weeks. Planned blinded dose reduction evaluations occurred at 24 and 52 weeks creating three periods of time between florbetapir scans: baseline‐24wk, 24wk‐52wk, or 52wk‐76wk. ANOVA were performed to compare baseline parameters.ResultAt 24wk, 15 participants in the donanemab group were assigned to 700mg dose and 19 were assigned to placebo. At 52wk, 10 participants were assigned to 700mg dose and 8 were assigned to placebo. In the 17 participants that remained on 1400mg donanemab until the end of the trial, amyloid reduction rate decreased during baseline‐24wk, 24wk‐52wk, and 52wk‐76wk (mean (SD): ‐2.7(1.5), ‐1.0 (0.7), and ‐0.5 (0.5) CL/wk, respectively). At the end of the trial, 5 out of 17 participants that remained in the 1400mg group became amyloid negative. In the 15 participants that were assigned to 700mg at 24wk, plaque lowering rate decreased from an average of ‐3.0 (1.2) CL/wk over the first 24wk to an average of ‐0.4 (0.4) CL/wk over 24wk‐52wk. At the end of the trial, 13 participants assigned to 700mg donanemab Q4W at 24wk became amyloid negative. Patients that received placebo at 24wk‐76wk (n=19) or 52wk‐76wk (n=19), had no re‐accumulation (mean (SD): 0.0 (0.1) CL/wk and ‐0.1 (0.2) CL/wk, respectively). Participants that stayed on 1400mg until study end had higher baseline amyloid (p=0.0000) and tau (p=0.0488) and were younger (p=0.0472) than those assigned to 700mg or placebo at 24wk.ConclusionDonanemab treatment reduced amyloid plaques and resulted in no re‐accumulation of amyloid over 1 year.

Collagen fibrils and cell nuclei are entrapped within Randall's plaques but not in CaOx matrix overgrowth: A microscopic inquiry into Randall's plaque stone pathogenesis.

Calcium oxalate (CaOx) stones can grow attached to the renal papillary calcification known as Randall's plaque. Although stone growth on Randall's plaque is a common phenomenon, this mechanism of stone formation is still poorly understood. The objective of this study was to investigate the microenvironment of mature Randall's plaque, explore its molecular composition and differentiate plaque from CaOx overgrowth using multimodal imaging on demineralized stone sections. Fluorescence imaging showed consistent differences in autofluorescence patterns between Randall's plaque and calcium oxalate overgrowth regions. Second harmonic generation imaging established the presence of collagen only in regions of decalcified Randall's plaque but not in regions of CaOx overgrowth matrix. Surprisingly, in these stone sections we observed cell nuclei with preserved morphology within regions of mature Randall's plaque. These conserved cells had variable expression of vimentin and CD45. The presence of nuclei in mature plaque indicates that mineralization is not necessarily associated with cell death. The markers identified suggest that some of the entrapped cells may be undergoing dedifferentiation or could emanate from a mesenchymal or immune origin. We propose that entrapped cells may play an important role in the growth and maintenance of Randall's plaque. Further characterization of these cells and thorough analyses of the mineralized stone forming renal papilla will be fundamental in understanding the pathogenesis of Randall's plaque and CaOx stone formation.

Gingivitis resolution followed by optical coherence tomography and fluorescence imaging: A case study.

Gingivitis is highly prevalent in adults, and if left untreated, can progress to periodontitis. In this article, we present an interesting case study where the resolution of gingivitis was followed over a period of 10 days using optical coherence tomography (OCT) and light-induced autofluorescence (LIAF). We demonstrate that OCT and its functional angiography can distinctively capture the changes during the resolution of gingivitis; while LIAF can detect red-fluorescent signals associated with mature plaque present at the inflamed site. The acute inflammatory region showed evidence of angiogenesis based on the quantification of vessel density and number; while no angiogenesis was detected within the less inflamed region. Gingival thickness showed a reduction of 140 ± 26 μm on average, measured between the peak gingivitis event and the period wherein the inflammation was resolved. Vessels in the angiogenesis site was found to reduce exponentially. The mildly inflamed site showed a decreasing trend in the vessel size, which however was within the error of the measurement.

The temporal shift of peri-implant microbiota during the biofilm formation and maturation in a canine model

ObjectivesAlthough the mature peri-implant biofilm composition is well studied, there is very little information on the succession of in vivo dental implant colonization. The aim of this study was to characterize the temporal changes and diversity of peri-implant supra-mucosal and sub-mucosal microbiota during the process of the plaque maturation. Materials and methodsDental implants (n = 25) were placed in the mandible of 3 beagle dogs. Illumina MiSeq sequencing of the hypervariable V3-V4 region of the 16S rRNA gene amplicons was used to characterize the supra/sub-mucosal microbiota in the peri-implant niches at 1day (T1), 7days (T2), 14days (T3), 21days (T4) and 28days (T5) after Phase Ⅱ surgery of the healing abutment placement. QIIME, Mothur, LEfSe and R-package were used for downstream analysis. ResultsA total of 1184 operational taxonomic units (OTUs), assigned into 22 phyla, 264 genera and 339 species were identified. In supra-mucosal niches, the alpha parameters of shannon, sobs and chao1 displayed significant differences between T1 and other time-points. However, in sub-mucosal niches, only sobs, chao1, and ace indexes displayed significant differences between T1 and T3, and T1 and T5. Beta-diversity showed statistically significant difference between T1 and T2, T3, T4, T5 within both sub-mucosal and supra-mucosal plaque. The phyla Bacteroidetes, Proteobacteria and Firmicutes were the most dominant phyla of both sub-mucosal and supra-mucosal niches at all time-points and Firmicutes increased during the maturation of peri-implant plaque. At the genus level, Neisseria decreased significantly after T1 suggesting the establishment of an anaerobic microenvironment. A decrease of Porphyromonas during the formation of sub-mucosal microbial community was also detected. Co-occurrence network analysis exhibited a more complicated co-occurrence relationship of bacterial species in the sub-mucosal niches. Fusobacterium nucleatum, Filifactor villosus, and some other species may play a crucial role in biofilm maturation. ConclusionsThe present results suggested that the development of peri-implant biofilm followed a similar pattern to dental plaque formation. Sub-mucosal biofilm may go through a more complicated procedure of maturation than supra-mucosal biofilm.

Research progress in the interaction between Treponema denticola and microorganisms of subgingival plaque

Treponema denticola (Td) is a gram-negative anaerobic bacterium closely related to the occurrence and development of periodontal disease and it accounts for a considerable proportion of mature plaque. As a later colonizer of the subgingival plaque biofilm, Td may have complex interactions with earlier and concurrent colonists including symbiotic relationship as while as synergistic or antagonistic effects under the regulation of quorum sensing molecules. Adhesin and coaggregation, mediated by a series of surface molecules, are the basis of the interaction. These interactions are ultimately manifested as gene expression changes in metabolism and virulence, in which are mainly metabolism changes with up- or down-regulation of multiple enzymes related to amino acid metabolism. This article reviews the related researches on the interaction between Td and microorganisms of subgingival plaque.

The Oral Microbiota Changes in Orthodontic Patients and Effects on Oral Health: An Overview.

Nowadays, there is a considerable interest to study the biological and microbiological changes that accompany orthodontic treatment. Growing knowledge on oral microbiota allows, day after day, to identify and characterize the microbial arrangements specifically associated with oral and extra-oral conditions. The aim of the present work is to highlight any further correlations between orthodontic appliances and the qualitative and quantitative modifications of the oral microbiota, such as predisposing factors for the onset of caries, periodontal diseases, and other infections, which can impact the oral and systemic health of the orthodontic patients. When compared with subjects without orthodontic appliances, orthodontic patients reported significant qualitative and quantitative differences in supra- and subgingival plaque during the entire treatment period. Certain components of fixed appliances (mainly bonded molar brackets, ceramic brackets, and elastomeric ligatures) showed high risks of periodontal disease and tooth decay for patients. An unclear prevalence of Candida spp. and the paucity of studies on viruses and protozoas in the oral microbiota of orthodontic patients need to be further investigated. The evidence emerging from this study could guide clinicians in modulating the timing of controls and enhance patient motivation to prevent the formation of mature plaque, thus reducing the risks of oral-plaque-related diseases.

Novel Phosphorylation-State Specific Antibodies Reveal Differential Deposition of Ser26 Phosphorylated Aβ Species in a Mouse Model of Alzheimer's Disease.

Aggregation and deposition of amyloid-β (Aβ) peptides in extracellular plaques and in the cerebral vasculature are prominent neuropathological features of Alzheimer’s disease (AD) and closely associated with the pathogenesis of AD. Amyloid plaques in the brains of most AD patients and transgenic mouse models exhibit heterogeneity in the composition of Aβ deposits, due to the occurrence of elongated, truncated, and post-translationally modified Aβ peptides. Importantly, changes in the deposition of these different Aβ variants are associated with the clinical disease progression and considered to mark sequential phases of plaque and cerebral amyloid angiopathy (CAA) maturation at distinct stages of AD. We recently showed that Aβ phosphorylated at serine residue 26 (pSer26Aβ) has peculiar characteristics in aggregation, deposition, and neurotoxicity. In the current study, we developed and thoroughly validated novel monoclonal and polyclonal antibodies that recognize Aβ depending on the phosphorylation-state of Ser26. Our results demonstrate that selected phosphorylation state-specific antibodies were able to recognize Ser26 phosphorylated and non-phosphorylated Aβ with high specificity in enzyme-linked immunosorbent assay (ELISA) and Western Blotting (WB) assays. Furthermore, immunofluorescence analyses with these antibodies demonstrated the occurrence of pSer26Aβ in transgenic mouse brains that show differential deposition as compared to non-phosphorylated Aβ (npAβ) or other modified Aβ species. Notably, pSer26Aβ species were faintly detected in extracellular Aβ plaques but most prominently found intraneuronally and in cerebral blood vessels. In conclusion, we developed new antibodies to specifically differentiate Aβ peptides depending on the phosphorylation state of Ser26, which are applicable in ELISA, WB, and immunofluorescence staining of mouse brain tissues. These site- and phosphorylation state-specific Aβ antibodies represent novel tools to examine phosphorylated Aβ species to further understand and dissect the complexity in the age-related and spatio-temporal deposition of different Aβ variants in transgenic mouse models and human AD brains.

Reactive oxygen species-dependent release of damage-associated molecular patterns from human gingival epithelial Ca9-22 cells during butyrate or propionate exposure.

Treating the gingival epithelial Ca9-22 cell with butyrate, a short-chain fatty acid (SCFA) produced by bacteria within mature dental plaque, induces necrotic cellular death. In this report, it was examined whether SCFA-mediated cellular death is accompanied by a release of damage-associated molecular patterns (DAMPs). In addition, the role of reactive oxygen species (ROS) in the release of DAMPs was evaluated. Human gingival epithelial Ca9-22 cells were treated with butyrate or propionate. The amounts of dead cells were then measured using SYTOX-green dye. Released DAMPs were detected by western blot. The role of ROS scavengers, ascorbic acid and N-acetylcysteine, on DAMP-release was evaluated. Dose and time-dependent induction of Ca9-22 cell death was observed during butyrate and propionate treatments. This was accompanied by the release of DAMPs. Ascorbic acid or N-acetylcysteine reduced cellular death and inhibited DAMP-release induced by exposure to butyrate or propionate. These data collectively suggest that SCFA-induced death of gingival epithelial Ca9-22 cells and accompanying release of DAMPs are dependent on ROS.