Plaque Accumulation Research Articles

Exosomes in Atherosclerosis: Role in the Pathogenesis and Targets for Therapy.

Atherosclerotic cardiovascular disease (ASCVD) is an advanced chronic inflammatory disease and the leading cause of death worldwide. The pathological development of ASCVD begins with atherosclerosis, characterised by a pathological remodelling of the arterial wall, lipid accumulation and build-up of atheromatous plaque. As the disease advances, it narrows the vascular lumen and limits the blood, leading to ischaemic necrosis in coronary arteries. Exosomes are nano-sized lipid vesicles of different origins that can carry many bioactive molecules from their parental cells, thus playing an important role in intercellular communication. The roles of exosomes in atherosclerosis have recently been intensively studied, advancing our understanding of the underlying molecular mechanisms. In this review, we briefly introduce exosome biology and then focus on the roles of exosomes of different cellular origins in atherosclerosis development and progression, functional significance of their cargoes and physiological impact on recipient cells. Studies have demonstrated that exosomes originating from endothelial cells, vascular smooth muscle cells, macrophages, dendritic cells, platelets, stem cells, adipose tissue and other sources play an important role in the atherosclerosis development and progression by affecting cholesterol transport, inflammatory, apoptotic and other aspects of the recipient cells' metabolism. MicroRNAs are considered the most significant type of bioactive molecules transported by exosomes and involved in ASCVD development. Finally, we review the current achievements and limitations associated with the use of exosomes for the diagnosis and treatment of ASCVD.

Cacao consumption improves passive avoidance memory impairment in a rat model of Alzheimer's disease: the role of hippocampal synaptic plasticity and oxidative stress.

Introduction: Alzheimer's disease (AD) causes progressive loss of cognitive function and synaptic plasticity, which is the most common form of dementia. The present study was designed to scrutinize the effects of cacao on passive avoidance memory function and to identify the roles of hippocampal synaptic plasticity and oxidative stress in an AD rat model induced by unilateral intracerebroventricular (UICV) injection of amyloid-beta (Aβ). Methods: Oral administration of cacao (500 mg/kg/ day) was given for 2 consecutive months. A memory retention test was conducted 24 h after passive avoidance training was completed. Subsequently, the amplitude of population spike (PS) and slope of field excitatory postsynaptic potentials (fEPSPs) were assessed at hippocampal long-term potentiation (LTP) in perforant pathway-dentate gyrus (PP-DG) synapses. Moreover, total thiol group (TTG) and malondialdehyde (MDA) concentrations were evaluated in the plasma. Furthermore, compact Aβ plaques were detected in the hippocampal DG by performing Congo red staining. Results: As a result of AD induction, passive avoidance memory was impaired; also, reduced fEPSP slopes, PS amplitudes, and content of TTG, and increase in MDA levels in the rats were observed. In contrast, cacao treatment ameliorated passive avoidance memory impairment, improved hippocampal LTP impairment, modulated oxidative-antioxidative status, and delayed Aβ plaques production in AD rats. Disscussion: Conclusively, cacao alleviates Aβ-induced cognitive deficit, probably by the amelioration of hippocampal LTP impairment, modulation of oxidative-antioxidative status, and inhibition of Aβ plaque accumulation.

Abstract 3114: Time Course Multi-omics Approach Investigating Gene Expression Regulation During Vascular Smooth Muscle Cell Phenotypic Transitioning

Coronary artery disease (CAD) is the leading cause of death in the United States. There is a need for novel therapeutic targets that prevent life-threatening consequences directly associated with plaque accumulation in the vascular wall—the underlying cause of CAD. During the progression of atherosclerosis, vascular smooth muscle cells (VSMCs) transdifferentiate from a contractile to a synthetic phenotype that can either promote fibrous cap stability (fibroblast-like) or contribute to inflammation and plaque accumulation (macrophage or osteoblast-like).The molecular mechanisms driving the functional phenotypic switching of VSMCs are not fully understood and represent a unique opportunity for discovering new treatments directly targeting plaque formation in the vascular wall. We measured gene expression regulation during VSMC dedifferentiation using time-course chromatin remodeling (ATACseq) and nascent transcription data (PROseq). We stimulated VSMCs from three healthy heart transplant donors with PDGF-BB for 0, 4, 8, 12, and 16 hours and performed sequencing in duplicate for each donor at each time point for a total of 30 PROseq and 30 ATACseq libraries. We identified 231,315 regions of accessible chromatin (peaks) in the ATACseq data and 12,954 genes in the PROseq data across the five time points. Likelihood ratio testing detected 13,285 peaks and 7,438 genes with time-dynamic changes in read counts representing six patterns of variable accessibility and nascent transcription following PDGF-BB stimulation: gradual increase/decrease (I/D), immediate I/D, and transient I/D. Transcription factor binding site (TFBS) motif enrichment of dynamic peaks revealed 31 TFs unique to one time dynamic. We identified 157 genes directly downstream of peaks enriched for the 31 TFBSs sharing similar time-specific fold changes. THAP1 binding site motifs had the highest number of cis-regulatory connections (596) and downstream genes (80). Our results capture the first ever time-course ATACseq and PROseq analysis conducted in human VSMCs and provide the ability to predict regulatory edges between TFs and genes in order to map the regulatory cascading events occurring during VSMC switching from a contractile to a synthetic state.

Abstract 1020: Comparative Assessment Of Hscrp And Apolipoprotein B As Ascvd Risk Biomarkers

According to the American Heart Association, the accumulation of plaque in the walls of arteries is identified as the primary cause of atherosclerotic cardiovascular disease (ASCVD). Currently, ASCVD-related conditions remain the leading cause of morbidity and mortality globally. Apolipoprotein B has been identified as a more precise cardiovascular risk marker than LDL-C, while hsCRP has shown potential as a cardiovascular disease indicator. This study aims to investigate the diagnostic performance and routine screening cut-off of hsCRP for early atherosclerosis vascular diseases (ASCVD) risk in adult patients, comparing it with Apo B. Objective: To compare the diagnostic performance of high-sensitivity C-reactive protein (hsCRP) with apolipoprotein B in assessing ASCVD risk. Method: A sample of 494 individuals from the NHANES 2015-2016 laboratory dataset, with a mean age greater than 17 years, was used for this study. ASCVD risk was measured by non-HDL-C, categorized into low and high risk based on the Mayo Clinic reference range. Predictors included Apo B, and hs-CRP. Binomial logistic regression and ROC curve analyses were conducted using the generalised linear models and pROC packages in RStudio IDE. Hypotheses were validated at p≤0.05, and diagnostic performance metrics such as ROC AUC, sensitivity, and specificity were measured on a scale of 0-1. Result: The findings revealed that for every 1g/L increase in apo B concentration, the odds of high ASCVD risk were approximately 3.8 х1011 times higher. Additionally, the model indicated that the odds of high ASCVD risk were 1.03 times higher for every 1mg/L increase in hsCRP concentration. However, this indicate that hsCRP level was not associated with odds of ASCVD risk. The ROC AUC for apo B and hsCRP were approximately 0.9739 and 0.6165, respectively, with cut-off values (sensitivity, specificity) of approximately 0.9g/L (0.927, 0.897) and 2.4 mg/L (0.596, 0.601), respectively. Thus, levels above these thresholds for both apo B and hsCRP are associated with high ASCVD risk. Conclusion: The study demonstrates that apo B exhibits high discriminatory and diagnostic accuracy, making it a suitable ASCVD risk biomarker compared to hsCRP. While hsCRP shows moderate diagnostic accuracy, it is not sufficient as a standalone ASCVD risk diagnostic marker. Therefore, apo B could serve as a replacement for LDL-C, while hsCRP could possibly serve as an add-on test in ASCVD risk assessment.

Abstract 1043: Single-cell Characterization Of Mouse Aorta During Atherosclerosis Regression

Atherosclerosis is a cardiovascular disease characterized by the accumulation of fibro-fatty plaque in the arteries. Over half the cells in a mature atherosclerotic lesion are smooth muscle cells (SMCs) or SMC-derived cells (SDCs). SMCs can undergo a process called phenotypic switching, which involves dedifferentiation to an intermediate multipotent cell state, migration, and transdifferentiation into alternative cell types (SDCs). Increased SMC phenotypic switching is associated with worse atherosclerosis progression. However, little is known of the roles of SMCs and SDCs in atherosclerosis regression. We hypothesize that SDCs may promote plaque stability during atherosclerosis regression. In this study, we used an SMC lineage tracing mouse model (Ldlr–/–; LoxP-stop-LoxP-ZsGreen1+/-; Myh11-CreERT2+/-) that is limited to male mice. At 6 weeks of age, the mice were administered a tamoxifen diet for 1 week, followed by a week of chow diet. Mice were then fed a 16-week Western diet to induce atherosclerosis. We modeled lipid-lowering induced regression by switching to chow diet and administering HDAd-hLDLR. Mice were harvested at timepoints 0, 2, 5, 10, and 20 weeks. Arterial tissues, such as the aorta, brachiocephalic artery, and aortic root were used for histological characterization of disease and for single cell RNA-sequencing (scRNA-seq). The scRNA-seq data showed no major changes in SMC and SDC cell clusters, showing that our hypothesis was likely null. We noted an overall decrease in macrophages, and an increase in both of the two fibroblast clusters, which also had transcriptional signatures of increased proliferation and reduced apoptosis and senescence. Our histology data showed thicker fibrous caps and increased collagen, as expected in a regression model. Going forward, we will assess whether one or both fibroblast clusters are necessary for the stabilization of plaques during atherosclerosis regression.

Synthesis and toxicity evaluation of a spray consisting of silver nanoparticles, ethylenediaminetetraacetic acid, methylsulfonylmethane, and xylitol on vero cell line

Abstract Introduction: Dental plaque is a biofilm or an accumulation of bacteria that grows in the internal surfaces of the mouth and can be observed as a white to pale yellow layer over or between teeth. The continuous formation and accumulation of dental plaque lead to oral diseases. As a result, it is necessary to prevent the aggregation of dental plaque and clean it daily. Recently, ethylenediaminetetraacetic acid (EDTA) has been utilized in toothpaste to prevent plaque formation as an EDTA-transporting enhancer, methylsulfonylmethane (MSM) can effectively increase its local effect. Xylitol decreases the Streptococcus mutans count by changing the metabolic pathways. Aims: In the present study, we synthesized a solution containing silver nanoparticles, EDTA, MSM, and xylitol and evaluated its toxicity on the Vero cell line through the MTT assay. Materials and Methods: To produce silver nanoparticles, we dissolved silver nitrate in sodium citrate. Then we used a solution of distilled water and polyvinylpyrrolidone, which resulted in the encapsulation and stabilization of silver nanoparticles, and the solution was made by mixing other ingredients. We evaluated the cytotoxicity of this spray using the Vero cell line. We cultured the cells in the 10% FBS-containing RPMI culture medium. For performing the cytotoxicity test, we put 10,000 cells in each well of the 96-well plate, and the next day added the synthesized solution to each well at dilutions 0.05%, 0.1%, 0.2%, 0.5%, 1%, 2%, 5%, and 10%. As the control group, we used 4 wells containing live Vero cells without adding the solution. After 24, 48, and 72 h, we added the MTT solution to each well and incubated the plates at 37°C for 4 h. Finally, we evaluated the rate of living cells by reading the absorbance with an ELISA device at 570 nm. Results and Discussion: We used the Mann–Whitney nonparametric test to evaluate the cytotoxicity of different concentrations of the synthesized spray solution and compare the cell viability rate of groups with the controls in various periods. According to the cytotoxicity results of different concentrations of the spray solution on the Vero cell line, there was no significant difference in cytotoxicity between the 0.05%, 0.1%, 0.2%, and 0.5%, and control groups at 24, 48, and 72 h (P > 0.05). No significant difference existed in cytotoxicity between 1% and 2% concentrations and the controls 24 h after exposure; this became significant after 48 and 72 h (P = 0.014). However, a significant difference existed in cytotoxicity between 5% concentration and the controls 24, 48, and 72 h after exposure (P = 0.014). The CC50 of the spray solution was calculated at 3.51%. Conclusion: The findings of this study showed that the synthesized solution is nontoxic; therefore, this spray solution can be used safely as an oral mouthwash and spray.

Macrophage Targeted Dendrimer-Tesaglitazar Therapy for Atherosclerosis

Background: Atherosclerosis is a leading contributor to cardiovascular disease, the number one cause of death globally. Although atherosclerosis is clearly a multicellular disease that also affects endothelial cells as well as smooth muscle cells of arteries, it is increasingly recognized as an inflammatory disease. Our goal is to determine if targeting immune cells implicated in atherosclerosis can halt plaque accumulation and resulting derangement of vascular cells in the aorta. Peroxisome proliferator activated receptors (PPARs) within macrophages present a promising therapeutic target as PPAR-α and PPAR-γ agonists have been shown to improve lipid metabolism and inhibit macrophage foam cell formation. However, due to high doses required and associated side effects, clinical translation was halted. We target anti-atherogenic pathways in immune cells using the novel treatment D-Tesa, a dendrimer conjugate of a dual PPAR-α/γ agonist, Tesaglitazar. Methods: 25-week-old, male, apolipoprotein E knockout (ApoE−/−) mice were fed high fat diet (HFD) for 16 weeks to induce atherosclerosis and randomized into two groups: 1) treatment group: D-Tesa for 6 weeks (20μg/kg twice weekly by oral gavage and 2) untreated group. HFD was continued for the duration of the study. Pulse wave velocity (PWV: Doppler), blood pressure (BP: tail cuff on trained, conscious mice), and body weight were monitored. Dendrimer mediated delivery of drug payload to plaque macrophages was studied using D-Cy5, a fluorescently labeled dendrimer, in an atherosclerotic mouse. Aortas were isolated and used for vasoreactivity studies and western blot analysis. THP-1 cell derived foam cells were used to study D-Tesa’s mechanism of action in vitro. Results: Immunofluorescence staining and confocal microscopy revealed that D-Cy5 localized in macrophages within the atherosclerotic plaque in ApoE−/− mice on HFD, indicating that the dendrimer can deliver drugs specifically into the plaque. D-Tesa slowed plaque progression, preserved endothelial function, and decreased arterial stiffness. BP was similar and unchanged between groups. D-Tesa surprisingly decreased body weight, which was the opposite effect observed from the free drug in clinical trials. Western blotting of aorta revealed that D-Tesa treated mice experienced an upregulation of PPAR-α, PPAR-γ, and ABCA1. The in vitro studies with THP-1 derived foam cells confirmed the upregulation of the cholesterol efflux pathway and anti-inflammatory benefit of D-Tesa. Conclusion: D-Tesa offers a novel therapy to ameliorate multiple damaging consequences of atherosclerosis on the cardiovascular system including improvements in plaque burden, endothelial function, arterial stiffness, and body weight in an ApoE−/− model of atherosclerosis. Excitingly, these effects were seen at 2-15 times lower doses despite continued HFD than those reported in literature with a combination of free Tesa and low-fat diet. Thus, D-Tesa offers great translational relevance because of potential reduction in negative side effects and higher patient benefit due to noted lack of compliance with dietary changes in the clinic. Further research is ongoing to evaluate sex differences, dose response, and long-term effects of this highly promising therapy. This work was supported by a NHLBI grant R01HL148112 01 (L.S.) and the Traystman Endowment (S.K.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effectiveness of Microneedling Technique Using Olive Oil on the Severity of Gingival Inflammation and Plaque Accumulation: A Randomised Controlled Trial.

Gingival inflammation, a hallmark of periodontal diseases, serves as a critical focus in oral health research. Characterized by redness, swelling, and bleeding of the gingival tissues, it reflects the body's response to bacterial biofilms accumulating on the tooth surfaces. This inflammatory process, initiated by the interaction between oral bacteria and the host immune system, can lead to a spectrum of periodontal conditions ranging from mild gingivitis to severe periodontitis. Understanding the efficacy of various methods to treat gingival inflammation is essential for refining treatment strategies and enhancing patient satisfaction in the realm of gingival inflammation. The objective of the study was to evaluate the efficacy of employing the microneedling technique with olive oil on gingival inflammation and plaque accumulation in individuals with gingivitis. Materials and methods:Twenty-four individuals diagnosed with plaque-induced gingivitis were selected from Saveetha Dental College, Chennai. Participants were randomly assigned to one of two groups: Group A, comprising 12 individuals who received mechanical periodontal treatment only andGroup B, consisting of 12 individuals treated with dermapen and topical olive oil. This involved the creation of microholes in the gingival tissue to enhance the concentration and penetration of the oils through the gingival tissues. Post-intervention assessments of gingival and plaque status were conducted using a gingival index and a plaque index at baseline, one, two, and four weeks. Statistical analysis was done using IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, NY, USA). Intergroup analysis was done using Mann-Whitney test and intra-group analysis was done using Kruskal-Wallis test for all the study parameters.Statistical significance was set at a p-value of less than 0.05. The mean plaque index scores were 2.02 ± 0.12 and 2.29 ± 0.21 in the subgingival scaling and microneedling with olive oil group respectively in baseline. The scores were 1.83 ± 0.29 and 0.57 ± 0.16in the subgingival scaling and microneedling with olive oil group respectively at the end of four weeks. The results of plaque index scores were statistically significant between the control and the intervened groups at the end of four weeks with a p value of 0.01*. The mean gingival index scores were 2.09 ± 0.16 and 2.37 ± 0.17 in the subgingival scaling and microneedling with olive oil group in the baseline respectively. The scores were 1.88 ± 0.23 and 0.96 ± 0.21 in the subgingival scaling and microneedling with olive oil group respectively at the end of four weeks. The results of gingival index scores were statistically significant between the control and the intervened groups at the end of four weeks with a p value of 0.01*. Our research showcased a novel and effective technique, unveiling a significant enhancement in gingival health accompanied by a reduction in both the average gingival index and plaque index.

Prevalence of oral Capnocytophaga species and their association with dental plaque accumulation and periodontal inflammation in middle‑aged and older people.

Capnocytophaga species are commonly found in human oral microbiome. The aim of the present study was to understand the association of the prevalence of oral Capnocytophaga species with oral hygiene and periodontal inflammation. A total of 136 patients (median age 72 years) who visited the Hiroshima University Hospital (Hiroshima, Japan) between April 2021 and June 2023 were enrolled. Swab samples were obtained from the tongue surface. DNA from Capnocytophaga species (C. ochracea and C. sputigena) was detected by real-time PCR analysis. Dental plaque accumulation was observed to assess the oral hygiene condition of participants. Additionally, clinical periodontal inflammation was assessed with periodontal inflamed surface area (PISA) scores. Clinical confounding factors such as age, sex, lifestyle-related disease, remaining teeth and denture wearing between Capnocytophaga species-positive and -negative groups were adjusted with a propensity score matching method. Mann-Whitney U and χ2 or Fisher's exact test were employed for statistical analysis. The prevalence rate was 67.6% for oral C. ochracea and 83.1% for C. sputigena. C. ochracea-positive participants showed significantly higher plaque control record scores (an indicator of dental plaque accumulation) than C. ochracea-negative participants (P=0.03). Additionally, C. ochracea/C. sputigena dual-positive participants exhibited significantly higher plaque control record and PISA scores than non-dual-positive participants (P=0.01 and P=0.04, respectively). Propensity score matching was conducted in the C. ochracea/C. sputigena dual-positive group and the non-dual-positive group for adjustment of clinical factors, resulting in 51 matched patient pairs. C. ochracea/C. sputigena dual-positive participants had significantly higher plaque control record scores than non-dual-positive participants (P=0.02). The present results suggest that the prevalence of both oral C. ochracea and C. sputigena is associated with poor oral hygiene in middle-aged and older people.

Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-β (Aβ) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aβ plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Histological evaluation of nonsurgical periodontal treatment with and without the use of sodium hypochlorite / amino acids and cross-linked hyaluronic acid gels in dogs

ObjectivesTo evaluate periodontal wound healing following scaling and root planing (SRP) in conjunction with the application of sodium hypochlorite/amino acids and cross-linked hyaluronic acid (xHyA) gels in dogs.Materials and MethodsIn four beagle dogs, 2-wall intrabony defects were created and metal strips were placed around the teeth. Clinical parameters were measured 4 weeks after plaque accumulation. The experimental root surfaces were subjected to SRP with either the subgingival application of a sodium hypochlorite/amino acid gel and a xHyA gel (test group) or SRP alone (control group) using a split-mouth design. Clinical parameters were re-evaluated at 6 weeks. The animals were sacrificed at 8 weeks for histological analysis.ResultsThe test group showed significant improvements in all clinical parameters compared to the control group. Histologically, the test group exhibited statistically significantly greater new bone formation [i.e., length of newly formed bone, new bone area] compared with the control group (p < 0.05). Furthermore, statistically significantly greater formation of new attachment [i.e., linear length of new cementum adjacently to newly formed bone with inserting collagen fibers] and new cementum was detected in the test group compared with the control group at 8 weeks (p < 0.05 and p < 0.01, respectively).ConclusionThe adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA gels to SRP offers an innovative novel approach to enhance periodontal wound healing/regeneration.Clinical relevanceThe present findings have for the first-time shown histologic evidence for periodontal regeneration in support of this novel treatment modality.

The effectiveness of water jet flossing and interdental flossing for oral hygiene in orthodontic patients with fixed appliances: a randomized clinical trial

BackgroundOrthodontic treatment presents challenges with plaque accumulation around brackets, archwires, and elastics, leading to retained plaque and gingival inflammation. Conventional toothbrushing may not be enough, requiring additional oral hygiene aids like interproximal brushes, dental flosses, and water flossers. Limited research exists on comparing water flossing and interdental flossing in orthodontic patients. Therefore, this study aims to assess their effectiveness in maintaining oral hygiene during active orthodontic treatment.MethodsA single-blind, randomized, parallel clinical study recruited orthodontic patients with full-mouth brackets and archwires. Thirty participants were randomly assigned to either water jet flossing or interdental flossing groups. All participants were instructed to brush twice daily with a provided toothbrush and toothpaste and use the assigned intervention once daily at night. Clinical measures, including the Gingival Bleeding Index (BI), Plaque Index (PI), and Gingival Index (GI), were recorded at baseline and day 14. Descriptive statistics and statistical tests were performed using SPSS software.ResultsThe water jet flossing group demonstrated a slightly higher, albeit non-significant, benefit in plaque removal (median difference of 6.79%%, P = 0.279) and bleeding reduction (median difference of 5.21%%, P = 0.172) compared to the interdental flossing group after two weeks. Both groups showed significant reductions in gingival bleeding index and plaque index from baseline to the 2-week follow-up. The interdental flossing group had median mean percentage differences of 16.13%% (plaque index) and 23.57% (gingival bleeding index), while the water jet flossing group had median percentage differences of 21.87% (plaque index) and 32.29% (gingival bleeding index). No significant changes in gingival index grades were observed in either group.ConclusionBoth water jet flossing and interdental flossing were effective in reducing plaque accumulation and gingival bleeding among orthodontic patients. While no significant differences were found between the two methods, water jet flossing showed a potential advantage. Further research is needed to validate its effectiveness, assess long-term impact, and understand its benefits for orthodontic patients.

The NeuroProtect Formula: A Preventive Approach to AD Targeting the HIF-1/PI3K-AKT Signaling Pathway Evaluated through In Vivo, In Vitro, and Network Pharmacology Approaches.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with limited options for reversing its middle-to-late stages. Early intervention is crucial to slow down disease progression. This study aimed to investigate the potential of the NeuroProtect (NP) formula, a combination of geniposide and Panax notoginseng saponins, in preventing AD. We evaluated the effects of the NP formula on amyloid plaque accumulation, neuronal degeneration, and molecular signaling pathways using in vivo and in vitro models. To predict functional pathways and potential downstream targets of NP intervention, we employed network pharmacology. The preventative impact of the NP formula was assessed using APP/PS1 mice. We conducted HE staining, ELISA assay, Golgi staining, and immunohistochemistry to detect the protective effect of NP. Additionally, cell experiments were performed to assess cell activity and target protein expression. Network pharmacology analysis revealed 145 drug-disease interactions and identified 5 core active targets associated with AD. Molecular docking results demonstrated strong binding affinity between the components of the NP formula (GP, GN-Rb1, GN-Rg1, NS-R1) and target proteins (STAT3, HIF1A, TLR4, mTOR, VEGFA). Notably, the binding energy between NS-R1 and mTOR was -11.4kcal/mol. Among the top 10 enriched KEGG pathways, the HIF-1 and PI3K-AKT signaling pathways were highlighted. In vivo experiments demonstrated that the NP formula significantly ameliorated pathological changes, decreased the Aβ42/Aβ40 ratio in the hippocampus and cortex, and increased dendritic spine density in the CA1 region during the early stage of AD. In vitro experiments further illustrated the NP formula's ability to reverse the inhibitory effects of Aβ25-35 on cell viability and regulate the expression of Tlr4, Mtor, Hif1a, Stat3, and Vegfa. Our findings suggest that NP exhibits neuroprotective effects during the early stages of AD, positioning it as a potential candidate for AD prevention. The NP formula may exert its preventive effects through the HIF-1/PI3K-AKT signaling pathway, with mTOR identified as a key target.

Randomized controlled clinical trial on the efficacy of a novel antimicrobial chewing gum in reducing plaque and gingivitis in adolescent orthodontic patients

ObjectivesChewing gums containing antiseptics or other antimicrobial substances may be effective in reducing plaque and gingivitis. Therefore, the aim of this randomized placebo-controlled clinical trial was to investigate the efficacy of a novel antimicrobial chewing gum containing essential oils (cinnamon, lemon, peppermint) and extracts on reduction of dental plaque and gingivitis as well as on oral health-related quality of life (OHRQoL) in adolescent orthodontic patients.Materials52 patients (11-22 years of age) were randomly assigned to use a test chewing gum (COVIDGUM, Clevergum) or a commercially available control chewing gum over a period of 10 days. Approximal plaque index (API), papillary bleeding index (PBI) and an OHRQoL questionnaire for children (COHIP-G19) were assessed at baseline (BL), after 10 days (10d) and 30 days (30d). In addition, oral health and oral hygiene related questions of the COHIP-G19 questionnaire were evaluated separately in subscales at each timepoint. Data were analyzed using non-parametrical statistical procedures (α = 0.05).ResultsAPI and PBI decreased significantly over time from BL to 10d and from BL to 30d in both groups, without significant differences between the groups. In both groups, the COHIP-G19 score, oral health subscale and oral hygiene subscale decreased significantly over time. Regarding the oral hygiene subscale, the test group showed significantly better scores at 30d (p = 0.011).ConclusionBoth chewing gums performed similarly effective in terms of reducing plaque accumulation and gingival inflammation and improving OHRQoL.Clinical relevanceChewing gums without antimicrobial ingredients may be sufficient to decrease plaque accumulation and gingival inflammation.

Impact of Type 1 Diabetes Mellitus on the Oral Health of Children –A Review

Diabetes mellitus (DM), is a metabolic disorder occurring when there is decreased production of insulin hormone or if there is poor body response to it. Type 1 DM is most common in children and adolescents and has a strong impact on their lifestyle. Conflicting evidence is available in the scientific literature on caries prevalence in children with diabetes and healthy children. Many studies have also reported higher plaque accumulation with greater gingival index scores in children with diabetes. Diabetes Mellitus plays a very noteworthy role in oral complications and therefore it becomes important for health practitioners to take good care of these children’s general and oral hygiene.

A Study on Use of Interdental Brushes among Patients Who are Undergoing Fixed Orthodontic Treatment: An Epidemiological Survey

Abstract Introduction Maintenance of periodontal health is very important during fixed orthodontic treatment as accumulation of plaque can cause dental challenges that may interfere with orthodontic treatment; hence the present investigation was carried out to examine the knowledge of patients who were using interdental brushes during fixed orthodontic treatment. Methods Total 150 subjects aged 14 to 30 years from Mangalore city were selected. Majority of them were in the age group of 14 to 18 years (39.33%). Overall, 77 females (51.3%) and 73 males (48.7%) who were undergoing fixed orthodontic treatment and had given consent for the participation in epidemiological questionnaire survey were included. Demographic information and use of interdental brushes during fixed orthodontic treatment for maintaining periodontal health were included in the survey. Result Overall, 58% of the participants undergoing fixed orthodontic treatment were using interdental brushes, which was statistically significant. The frequency of using interdental brush was 72.4%, 19.5%, and 8.04% daily, weekly, and monthly, respectively. Conclusion The majority of the study participants who sought fixed orthodontic treatment were using interdental brushes daily in order to maintain periodontal health, which was statistically significant. Patient education and motivation was shown to be strongly associated with maintaining of periodontal health among study participants.

MANAGEMENT OF BACTERIAL PLAQUE-INDUCED GINGIVAL ENLARGEMENT: CASE REPORT

Introduction: Gingival enlargement is a condition that we often encounter in the oral cavity. This condition can be caused by plaque accumulation, systemic disorders, and side effects of some drugs as well as genetic factors. Gingival enlargement due to the accumulation of bacterial plaque generally shows signs and symptoms of inflammation which can be a major risk factor for periodontitis. This case report aims to describe two cases of plaque-induced gingival enlargement, one of which was accompanied by the presence of granulomatous epulis. Case: The first case was a 23-year-old woman complaining that her gums often bleed when brushing her teeth since 1 year ago. Intra oral examination can see swelling of the gingiva in the anterior area of RA and RB. The second case is a 40-year-old woman with complaints of swelling of the lower right back gum since 2 years ago. An enlargement of the gingiva in the anterior area is seen accompanied by granulomatous epulis with fibrous consistency in the posterior area of RB. Treatment: In the first case, non-surgical treatment was carried out and continued with regular visits every 3 months. In the second case, non-surgical and surgical procedures were performed. Treatment begins with tooth root extraction and scaling and root planning. Furthermore, gingivectomy surgery was performed to excise the enlarged gingiva. Discussions: The treatment results look good, where it can be seen that the etiological factor can be ruled out. After the surgical treatment, the healing went well, marked by no inflammation around it. Conclusion: Gingival enlargement can affect aesthetics and interfere with the patient's masticatory function. Identification of the etiological factors is necessary for an appropriate treatment plan.

Impact of clear aligners on plaque and periodontal health

In recent years, clear aligners have become a well-liked substitute for traditional braces in orthodontic treatment. Examining the effects of clear aligners on periodontal health and plaque accumulation is the goal of this review. To examine pertinent studies that have been published up to this point, a comprehensive evaluation of the literature was carried out. The review includes research on the microbial alterations in tooth plaque composition that occur during clear aligner therapy and the subsequent impact on periodontal tissues. Clear aligners and traditional braces are also compared with respect to how they affect gingival health, periodontal disease prevalence, and oral hygiene practices.In terms of plaque control, the results imply that transparent aligners offer special benefits and challenges. An important factor influencing the microbiological environment in the oral cavity is patient compliance, the type of aligner used, and the subtleties of its design. Moreover, the effect of orthodontic therapies on periodontal health is explored, providing insight into possible associations between the use of clear aligners and periodontal results. By underlining the necessity of individualized oral hygiene management strategies during clear aligner therapy, this review offers orthodontic practitioners’ insightful information. It highlights the need of maintaining periodontal health throughout orthodontic treatment and stresses the necessity of a multidisciplinary approach to optimize patient outcomes. In summary, this comprehensive review provides an overview of the most recent findings regarding the impact of clear aligners on plaque and periodontal health. By teaching clinicians, researchers, and patients about the subtleties of oral hygiene care during orthodontic treatment, the findings are meant to direct the development of effective strategies for maintaining good periodontal health in patients getting clear aligner therapy.

Oral health knowledge, practice and associated factors among Junior High School students of Koforidua, Ghana: a cross-sectional study

BackgroundOral disease poses a significant public health burden for many countries and affects individuals throughout their lifetime, causing pain, disfigurement, impairment of function and reduced quality of life. Among children and adolescents globally, there is a recognized trend of poor oral hygiene, attributed to the accumulation of plaque and calculus deposits that increase with age. This study assessed the knowledge, practice and factors associated with the practice of oral hygiene among Junior High School students (JHS) in Koforidua, in the Eastern Region of Ghana.MethodsA school-based cross-sectional study design was conducted among 233 JHS students in Koforidua township using a multistage sampling technique. Descriptive and inferential statistics, including frequency, percentage, and Pearson’s Chi-square test, were conducted. The results were interpreted using tables and graphs.ResultsFindings from the study revealed that more than half 126 (54.1%) of the respondents had a good level of knowledge of oral hygiene. The majority 130 (55.8%) of them also had good oral hygiene practice. The findings further indicated that a significant relationship was found between the class or education level of students and good oral hygiene practice (χ2 = 17.36, p < 0.001).ConclusionOverall, the current study found that over half of the JHS students had good knowledge as well as practice of oral hygiene. This reinforces the significance of oral health education and awareness campaigns, especially in school settings, to improve knowledge, attitudes, and behaviours related to oral hygiene. The study however found only class or education level of students to be statistically associated with the practice of oral hygiene. While other variables did not reach statistical significance, our research serves as a starting point for further investigation and exploration of the various factors that may contribute to oral hygiene practices.

Preformed Stainless-Steel Crowns: Their Effects on Oral Hygiene Maintenance and Gingival Health – A Prospective Original Research

ABSTRACT The stainless-steel crown (SSC) is a durable restoration and has several indications for use in primary teeth such as following a pulpotomy/pulpectomy, fractured teeth, teeth with developmental defects, or large multi-surface caries lesions where amalgam is likely to fail. Due to its durability and a lifespan like the primary tooth, it could well be the gold standard in restorative care. SSCs protect the crown from fracture, reduce the possibility for leakage, and ensure a biological seal. However, the placement of the SSC should follow a meticulous technique. There are some clinical situations where the SSC may fail, leading to plaque accumulation and gingivitis. This could be secondary to improper crimping of crown margins, which lead to poorly adapted SSC. In some clinical situations, ledge formation under the crown or failure to clean excess cement can contact the gingiva and cause gingival inflammation. This study was carried out on 41 children between the ages of 4 and 10 in Al Qassim region to study the effects of SSCs on gingiva and oral hygiene. The study also aims to establish the correlation between SSC adaptation and post-insertion inflammation. The plaque and gingival index were recorded at 3 months’ post SSC insertion. Clinical examination was undertaken, and gingival index (Loe and Silness 1967) and plaque index (Silness and Loe 1967) were used to record gingival health and plaque accumulation, respectively. The result for post-inflammation and SSC adaptation showed that there was no statistically significant difference in post-insertion inflammation and crown adaptation (P value = 0.216). The result for pre-operative inflammation and post-operative inflammation shows that there is no significant difference in post-inflammation and adaptation (P value = 0.47). We found that oral hygiene care had a heightening effect and oral hygiene maintenance plays a key role in preventing gingival inflammation irrespective of the SSC adaptation over short periods of time (3 months).