scholarly journals Quercetin Preserves Oral Cavity Health by Mitigating Inflammation and Microbial Dysbiosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Erin C. Mooney ◽  
Sara E. Holden ◽  
Xia-Juan Xia ◽  
Yajie Li ◽  
Min Jiang ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Alveolar Bone ◽  
Treated Group ◽  
Oral Bacteria ◽  
Inflammatory Cell Infiltrate ◽  
Microbial Composition ◽  
Tlr Agonists ◽  
Microbial Dysbiosis

Failure to attenuate inflammation coupled with consequent microbiota changes drives the development of bone-destructive periodontitis. Quercetin, a plant-derived polyphenolic flavonoid, has been linked with health benefits in both humans and animals. Using a systematic approach, we investigated the effect of orally delivered Quercetin on host inflammatory response, oral microbial composition and periodontal disease phenotype. In vivo, quercetin supplementation diminished gingival cytokine expression, inflammatory cell infiltrate and alveolar bone loss. Microbiome analyses revealed a healthier oral microbial composition in Quercetin-treated versus vehicle-treated group characterized by reduction in the number of pathogenic species including Enterococcus, Neisseria and Pseudomonas and increase in the number of non-pathogenic Streptococcus sp. and bacterial diversity. In vitro, Quercetin diminished inflammatory cytokine production through modulating NF-κB:A20 axis in human macrophages following challenge with oral bacteria and TLR agonists. Collectively, our findings reveal that Quercetin supplement instigates a balanced periodontal tissue homeostasis through limiting inflammation and fostering an oral cavity microenvironment conducive of symbiotic microbiota associated with health. This proof of concept study provides key evidence for translational studies to improve overall health.

Nutritional Influences on Biofilm Development

1997 ◽  
Vol 11 (1) ◽  
pp. 81-99 ◽  
Author(s):  
G.H.W. Bowden ◽  
Y.H. Li
Keyword(s):  
Oral Cavity ◽  
Bacterial Species ◽  
Oral Bacteria ◽  
Carbon Limitation ◽  
Cell Surfaces ◽  
Nutritional Influences ◽  
Oral Biofilms ◽  
Biofilm Development

The amounts and types of nutrients in the environment influence the development and final bacterial and chemical composition of biofilms. In oligotrophic environments, organisms respond to nutrient stress by alterations in their cell morphology and cell surfaces, which enhance adherence. Little is known of the responses to stress by bacteria in the animal oral cavity. The environment in the oral cavity is less extreme, and saliva provides a constant source of nutrients. Catabolic cooperation among oral bacteria allows carbon and nitrogen from salivary glycoproteins to be utilized. Modification of growth environments of oral bacteria can influence their cell surfaces and adhesion. Studies in experimental animals have shown that feeding either glucose or sucrose diets or fasting has little effect on the initial stages of development of oral biofilms. However, diet can influence the proportions of different bacterial species later in biofilm development. Studies of competition among populations in communities of oral bacteria in vitro and in vivo have shown the significance of carbon limitation and excess and changes in environmental pH. Relatively few studies have been made of the role of a nitrogen metabolism in bacterial competition in biofilms. In keeping with biofilms in nature, oral biofilms provide a sequestered habitat, where organisms are protected from removal by saliva and where interactions among cells generate a biofilm environment, distinct from that of saliva. Oral biofilms are an essential component in the etiologies of caries and periodontal disease, and understanding the biology of oral biofilms has aided and will continue to aid in the prevention and treatment of these diseases.

scholarly journals Identification of Small-Molecule Inhibitors Targeting Porphyromonas gingivalis Interspecies Adherence and Determination of Their In Vitro and In Vivo Efficacies

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mohammad Roky ◽  
Jinlian Tan ◽  
Maryta N. Sztukowska ◽  
John O. Trent ◽  
Donald R. Demuth
Keyword(s):  
Oral Cavity ◽  
Cell Lines ◽  
Porphyromonas Gingivalis ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Alveolar Bone ◽  
Structural Similarity ◽  
Content Type

ABSTRACT Porphyromonas gingivalis is one of the primary causative agents of periodontal disease and initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of a minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (AgI/II). Our previous work identified an AgI/II peptide that potently inhibited adherence and significantly reduced P. gingivalis virulence in vivo, suggesting that this interaction represents a potential target for drug discovery. To develop targeted small-molecule inhibitors of this protein-protein interaction, we performed a virtual screen of the ZINC databases to identify compounds that exhibit structural similarity with the two functional motifs (NITVK and VQDLL) of the AgI/II peptide. Thirty three compounds were tested for in vitro inhibition of P. gingivalis adherence and the three most potent compounds, namely, N7, N17, and V8, were selected for further analysis. The in vivo efficacy of these compounds was evaluated in a murine model of periodontitis. Treatment of mice with each of the compounds significantly reduced maxillary alveolar bone resorption in infected animals. Finally, a series of cytotoxicity tests were performed against human and murine cell lines. Compounds N17 and V8 exhibited no significant cytotoxic activity toward any of the cell lines, whereas compound N7 was cytotoxic at the highest concentrations that were tested (20 and 40 μM). These results identify compounds N17 and V8 as potential lead compounds that will facilitate the design of more potent therapeutic agents that may function to limit or prevent P. gingivalis colonization of the oral cavity.

scholarly journals In VitroandIn VivoActivity of Peptidomimetic Compounds That Target the Periodontal PathogenPorphyromonas gingivalis

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Jinlian Tan ◽  
Pravin C. Patil ◽  
Frederick A. Luzzio ◽  
Donald R. Demuth
Keyword(s):  
Oral Cavity ◽  
Cell Line ◽  
Alveolar Bone ◽  
Potent Inhibitor ◽  
Protein A ◽  
Periodontal Pathogen ◽  
Oral Streptococci ◽  
Content Type

ABSTRACTThe interaction of the periodontal pathogenPorphyromonas gingivaliswith oral streptococci is important for initial colonization of the oral cavity byP. gingivalisand is mediated by a discrete motif of the streptococcal antigen I/II protein. A synthetic peptide encompassing this motif functions as a potent inhibitor ofP. gingivalisadherence, but the use of peptides as topically applied therapeutic agents in the oral cavity has limitations arising from the relatively high cost of peptide synthesis and their susceptibility to degradation by proteases expressed by oral organisms. In this study, we demonstrate thein vitroandin vivoactivity of five small-molecule mimetic compounds of the streptococcal peptide. Using a three-species biofilm model, all five compounds were shown to effectively inhibit the incorporation ofP. gingivalisintoin vitrobiofilms and exhibited 50% inhibitory concentrations (IC50s) of 10 to 20 μM. Four of the five compounds also significantly reduced maxillary alveolar bone resorption induced byP. gingivalisinfection in a mouse model of periodontitis. All of the compounds were nontoxic toward a human telomerase immortalized gingival keratinocyte cell line. Three compounds exhibited slight toxicity against the murine macrophage J774A.1 cell line at the highest concentration tested. Compound PCP-III-201 was nontoxic to both cell lines and the most potent inhibitor ofP. gingivalisvirulence and thus may represent a novel potential therapeutic agent that targetsP. gingivalisby preventing its colonization of the oral cavity.

scholarly journals Human Saliva-Mediated Hydrolysis of Eugenyl-β-D-Glucoside and Fluorescein-di-β-D-Glucoside in In Vivo and In Vitro Models

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 172
Author(s):  
Mariusz Dziadas ◽  
Adam Junka ◽  
Henryk Jeleń
Keyword(s):  
Oral Cavity ◽  
Control Sample ◽  
Rapid Test ◽  
Human Saliva ◽  
In Vitro Models ◽  
Microbial Hydrolysis ◽  
Amoxicillin Trihydrate ◽  
Potassium Clavulanate

Eugenyl-β-D-glucopyranoside, also referred to as Citrusin C, is a natural glucoside found among others in cloves, basil and cinnamon plants. Eugenol in a form of free aglycone is used in perfumeries, flavourings, essential oils and in medicinal products. Synthetic Citrusin C was incubated with human saliva in several in vitro models together with substrate-specific enzyme and antibiotics (clindamycin, ciprofloxacin, amoxicillin trihydrate and potassium clavulanate). Citrusin C was detected using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Citrusin C was completely degraded only when incubated with substrate-specific A. niger glucosidase E.C 3.2.1.21 (control sample) and when incubated with human saliva (tested sample). The addition of antibiotics to the above-described experimental setting, stopped Citrusin C degradation, indicating microbiologic origin of hydrolysis observed. Our results demonstrate that Citrusin C is subjected to complete degradation by salivary/oral cavity microorganisms. Extrapolation of our results allows to state that in the human oral cavity, virtually all β-D-glucosides would follow this type of hydrolysis. Additionally, a new method was developed for an in vivo rapid test of glucosidase activity in the human mouth on the tongue using fluorescein-di-β-D-glucoside as substrate. The results presented in this study serve as a proof of concept for the hypothesis that microbial hydrolysis path of β-D-glucosides begins immediately in the human mouth and releases the aglycone directly into the gastrointestinal tract.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

2021 ◽  
pp. 153473462110021
Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Plasma Treatment ◽  
Cold Plasma ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Control Group ◽  
Alpha Smooth Muscle Actin ◽  
Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

scholarly journals Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Shasha Xiang ◽  
Kun Ye ◽  
Mian Li ◽  
Jian Ying ◽  
Huanhuan Wang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Lactobacillus Reuteri ◽  
Carbon Sources ◽  
Short Chain Fatty Acids ◽  
Microbial Composition ◽  
Key Enzymes ◽  
Rrna Sequencing ◽  
Phosphate Acetyltransferase

Abstract Background Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts. Results In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate. Conclusions Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs.

scholarly journals Sulfasalazine modifies metabolic profiles and enhances cisplatin chemosensitivity on cholangiocarcinoma cells in in vitro and in vivo models

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Malinee Thanee ◽  
Sureerat Padthaisong ◽  
Manida Suksawat ◽  
Hasaya Dokduang ◽  
Jutarop Phetcharaburanin ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Treated Group ◽  
Control Group ◽  
High Recurrence Rate ◽  
Nucleic Acid Metabolism ◽  
In Vivo Models ◽  
Tryptophan Degradation ◽  
Xenograft Mice

Abstract Background Sulfasalazine (SSZ) is widely known as an xCT inhibitor suppressing CD44v9-expressed cancer stem-like cells (CSCs) being related to redox regulation. Cholangiocarcinoma (CCA) has a high recurrence rate and no effective chemotherapy. A recent report revealed high levels of CD44v9-positive cells in CCA patients. Therefore, a combination of drugs could prove a suitable strategy for CCA treatment via individual metabolic profiling. Methods We examined the effect of xCT-targeted CD44v9-CSCs using sulfasalazine combined with cisplatin (CIS) or gemcitabine in CCA in vitro and in vivo models and did NMR-based metabolomics analysis of xenograft mice tumor tissues. Results Our findings suggest that combined SSZ and CIS leads to a higher inhibition of cell proliferation and induction of cell death than CIS alone in both in vitro and in vivo models. Xenograft mice showed that the CD44v9-CSC marker and CK-19-CCA proliferative marker were reduced in the combination treatment. Interestingly, different metabolic signatures and significant metabolites were observed in the drug-treated group compared with the control group that revealed the cancer suppression mechanisms. Conclusions SSZ could improve CCA therapy by sensitization to CIS through killing CD44v9-positive cells and modifying the metabolic pathways, in particular tryptophan degradation (i.e., kynurenine pathway, serotonin pathway) and nucleic acid metabolism.

scholarly journals Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

2020 ◽  
Vol 34 ◽  
pp. 205873842097489
Author(s):  
Jiang Wang ◽  
Bo Wang ◽  
Xin Lv ◽  
Yingjie Wang
Keyword(s):  
Alveolar Bone ◽  
Immune Cell ◽  
Critical Role ◽  
Therapeutic Drug ◽  
Mice Model ◽  
T Helper 17 ◽  
Th17 Cell Differentiation ◽  
Tnf Α

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

scholarly journals Interaction of periodontitis and orthodontic tooth movement—an in vitro and in vivo study

2021 ◽  
Author(s):  
Birgit Rath-Deschner ◽  
Andressa V. B. Nogueira ◽  
Svenja Beisel-Memmert ◽  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Mechanical Strain ◽  
Orthodontic Tooth Movement ◽  
Fusobacterium Nucleatum ◽  
In Vivo Study ◽  
Rt Pcr ◽  
Periodontal Inflammation

Abstract Objectives The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2). Materials and methods The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA. Results Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro. Conclusions Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process. Clinical relevance Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again.

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