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1.
Veratridine Can Bind to a Site at the Mouth of the Channel Pore at Human Cardiac Sodium Channel NaV1.5.
Gulsevin, A, Glazer, AM, Shields, T, Kroncke, BM, Roden, DM, Meiler, J
International journal of molecular sciences. 2022;(4)
Abstract
The cardiac sodium ion channel (NaV1.5) is a protein with four domains (DI-DIV), each with six transmembrane segments. Its opening and subsequent inactivation results in the brief rapid influx of Na+ ions resulting in the depolarization of cardiomyocytes. The neurotoxin veratridine (VTD) inhibits NaV1.5 inactivation resulting in longer channel opening times, and potentially fatal action potential prolongation. VTD is predicted to bind at the channel pore, but alternative binding sites have not been ruled out. To determine the binding site of VTD on NaV1.5, we perform docking calculations and high-throughput electrophysiology experiments in the present study. The docking calculations identified two distinct binding regions. The first site was in the pore, close to the binding site of NaV1.4 and NaV1.5 blocking drugs in experimental structures. The second site was at the "mouth" of the pore at the cytosolic side, partly solvent-exposed. Mutations at this site (L409, E417, and I1466) had large effects on VTD binding, while residues deeper in the pore had no effect, consistent with VTD binding at the mouth site. Overall, our results suggest a VTD binding site close to the cytoplasmic mouth of the channel pore. Binding at this alternative site might indicate an allosteric inactivation mechanism for VTD at NaV1.5.
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2.
Study of oral microorganisms contributing to non-carious cervical lesions via bacterial interaction and pH regulation.
Huang, X, She, L, Liu, H, Liu, P, Chen, J, Chen, Y, Zhou, W, Lu, Y, Lin, J
Journal of cellular and molecular medicine. 2021;(6):3103-3112
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Abstract
There is a lack of evidence about the relationship between microorganisms and non-carious cervical lesions (NCCLs) due to limited technologies. A group of 78 patients was enrolled for microbial 16S rRNA sequencing of dental plaques on normal and defective cervical surfaces. Parallel data from 39 patients were analysed with paired t tests, and Fusobacteriales exhibited significantly less distribution on NCCLs than on normal surfaces. As a result, Fusobacterium nucleatum, the most common oral bacterial strain belonging to the order Fusobacteriales, was selected for further research. From a scanning electron microscopy (SEM) scan, the tooth surface with Fusobacterium nucleatum and Streptococcus mutans culture was more intact than that without Fusobacterium nucleatum. Furthermore, the calcium contents in groups with Fusobacterium nucleatum were significantly higher than that without it. In further mechanistic research, Fusobacterium nucleatum was demonstrated to adhere to and disturb other organisms as well as producing alkaline secretions to neutralize the deleterious acidic environment, protecting the tooth structure. In conclusion, microorganisms and NCCLs were confirmed directly related through adherent bacterial interactions and pH regulation. The research provides a new perspective and experimental evidence for the relation between microorganisms and NCCLs, which guides clinical treatment and preventive dentistry in the future.
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Assessment of real life eating difficulties in Parkinson's disease patients by measuring plate to mouth movement elongation with inertial sensors.
Kyritsis, K, Fagerberg, P, Ioakimidis, I, Chaudhuri, KR, Reichmann, H, Klingelhoefer, L, Delopoulos, A
Scientific reports. 2021;(1):1632
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder with both motor and non-motor symptoms. Despite the progressive nature of PD, early diagnosis, tracking the disease's natural history and measuring the drug response are factors that play a major role in determining the quality of life of the affected individual. Apart from the common motor symptoms, i.e., tremor at rest, rigidity and bradykinesia, studies suggest that PD is associated with disturbances in eating behavior and energy intake. Specifically, PD is associated with drug-induced impulsive eating disorders such as binge eating, appetite-related non-motor issues such as weight loss and/or gain as well as dysphagia-factors that correlate with difficulties in completing day-to-day eating-related tasks. In this work we introduce Plate-to-Mouth (PtM), an indicator that relates with the time spent for the hand operating the utensil to transfer a quantity of food from the plate into the mouth during the course of a meal. We propose a two-step approach towards the objective calculation of PtM. Initially, we use the 3D acceleration and orientation velocity signals from an off-the-shelf smartwatch to detect the bite moments and upwards wrist micromovements that occur during a meal session. Afterwards, we process the upwards hand micromovements that appear prior to every detected bite during the meal in order to estimate the bite's PtM duration. Finally, we use a density-based scheme to estimate the PtM durations distribution and form the in-meal eating behavior profile of the subject. In the results section, we provide validation for every step of the process independently, as well as showcase our findings using a total of three datasets, one collected in a controlled clinical setting using standardized meals (with a total of 28 meal sessions from 7 Healthy Controls (HC) and 21 PD patients) and two collected in-the-wild under free living conditions (37 meals from 4 HC/10 PD patients and 629 meals from 3 HC/3 PD patients, respectively). Experimental results reveal an Area Under the Curve (AUC) of 0.748 for the clinical dataset and 0.775/1.000 for the in-the-wild datasets towards the classification of in-meal eating behavior profiles to the PD or HC group. This is the first work that attempts to use wearable Inertial Measurement Unit (IMU) sensor data, collected both in clinical and in-the-wild settings, towards the extraction of an objective eating behavior indicator for PD.
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Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential.
Hoffmann, W
International journal of molecular sciences. 2021;(22)
Abstract
Human saliva is a complex body fluid with more than 3000 different identified proteins. Besides rheological and lubricating properties, saliva supports wound healing and acts as an antimicrobial barrier. TFF peptides are secreted from the mucous acini of the major and minor salivary glands and are typical constituents of normal saliva; TFF3 being the predominant peptide compared with TFF1 and TFF2. Only TFF3 is easily detectable by Western blotting. It occurs in two forms, a disulfide-linked homodimer (Mr: 13k) and a high-molecular-mass heterodimer with IgG Fc binding protein (FCGBP). TFF peptides are secretory lectins known for their protective effects in mucous epithelia; the TFF3 dimer probably has wound-healing properties due to its weak motogenic effect. There are multiple indications that FCGBP and TFF3-FCGBP play a key role in the innate immune defense of mucous epithelia. In addition, homodimeric TFF3 interacts in vitro with the salivary agglutinin DMBT1gp340. Here, the protective roles of TFF peptides, FCGBP, and DMBT1gp340 in saliva are discussed. TFF peptides are also used to reduce radiotherapy- or chemotherapy-induced oral mucositis. Thus, TFF peptides, FCGBP, and DMBT1gp340 are promising candidates for better formulations of artificial saliva, particularly improving wound healing and antimicrobial effects even in the esophagus.
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Oral probiotic activities and biosafety of Lactobacillus gasseri HHuMIN D.
Mann, S, Park, MS, Johnston, TV, Ji, GE, Hwang, KT, Ku, S
Microbial cell factories. 2021;(1):75
Abstract
BACKGROUND Lactobacillus spp. have been researched worldwide and are used in probiotics, but due to difficulties with laboratory cultivation of and experimentation on oral microorganisms, there are few reports of Lactobacillus spp. being isolated from the oral cavity and tested against oral pathogens. This research sought to isolate and determine the safety and inhibitory capabilities of a Lactobacillus culture taken from the human body. RESULTS One organism was isolated, named "L. gasseri HHuMIN D", and evaluated for safety. A 5% dilution of L. gasseri HHuMIN D culture supernatant exhibited 88.8% inhibition against halitosis-producing anaerobic microorganisms and the organism itself exhibited powerful inhibitory effects on the growth of 11 oral bacteria. Hydrogen peroxide production reached 802 μmol/L after 12 h and gradually diminished until 24 h, it efficiently aggregated with P. catoniae and S. sanguinis, and it completely suppressed S. mutans-manufactured artificial dental plaque. L. gasseri HHuMIN D's KB cell adhesion capacity was 4.41 cells per cell, and the cell adhesion of F. nucleatum and S. mutans diminished strongly in protection and displacement assays. CONCLUSION These results suggest that L. gasseri HHuMIN D is a safe, bioactive, lactobacterial food ingredient, starter culture, and/or probiotic microorganism for human oral health.
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Optimized liquid-based cytology for the cellular and molecular analysis of oral keratinocytes: A promising diagnostic tool.
Osorio-Osorno, YA, Arboleda Toro, D, Arango, JC, Parada-Sanchez, MT
Diagnostic cytopathology. 2021;(1):96-104
Abstract
BACKGROUND Liquid-based cytology (LBC) has improved exfoliative cytology by facilitating the extraction of more precise information from epithelial cells. The aim of this study was to optimize a protocol using a conventional cytobrush to perform LBC, obtaining oral keratinocytes for their further cellular and molecular analysis. METHODS LBC was performed in 30 healthy donors from buccal mucosa. We evaluated the use of diethyl pyrocarbonate (DEPC)-treated Dulbecco's Modified Eagle Medium (DMEM) medium right after the collection of the cells. Cell morphology and viability were determined by Orcein staining and flow cytometry, respectively. RNA was extracted by the trizol method, and evaluated with spectrometry and electrophoresis. Finally, RNA was copied into cDNA and GAPDH and TLR2 genes were amplified by reverse transcription polymerase chain reaction (RT-PCR) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) using specific primers. RESULTS Only DEPC-treated DMEM preserved the viability of intact intraepithelial keratinocytes. RNA quantity and quality improves in samples treated with DEPC. RNA integrity is comparable with a cell line control. GAPDH gene was successfully amplified by RT-PCR and RT-qPCR. CONCLUSIONS Therefore, LBC performed under these conditions becomes a reproducible technique for the retrieval of intraepithelial oral keratinocytes with good cell viability for cytomorphometric analysis, and extraction of good RNA quality suitable for molecular analyses such as PCR. We propose this LBC protocol as a complementary method to the cellular and molecular study of oral mucosa pathologies; however, it requires further study.
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Impact of Oropharyngeal Administration of Colostrum in Preterm Newborns' Oral Microbiome.
Cortez, RV, Fernandes, A, Sparvoli, LG, Padilha, M, Feferbaum, R, Neto, CM, Taddei, CR
Nutrients. 2021;(12)
Abstract
The initial colonization of the human microbiota is of paramount importance. In this context, the oropharyngeal administration of colostrum is a safe, viable, and well-tolerated practice even by the smallest preterm infants. Therefore, this study evaluated the effects of oropharyngeal administration of colostrum on the establishment of preterm infants' oral microbiota. A longitudinal observational study was carried out with 20 premature neonates, divided into two groups: one receiving the protocol (Oropharyngeal Administration of Colostrum; OAC) and the other one receiving Standard Caare (SC). Saliva samples were collected from the newborns weekly during the study period (from the day of birth until the 21st day of life) for analysis of oral microbiota through 16S rRNA gene sequencing. We observed that the colonization of the oral microbiota of preterm newborns preseanted a higher relative abundance of Staphylococcus on the 7th day of life, mainly in the OAC group. Additionally, an increased abundance of Bifidobacterium and Bacteroides was observed in the OAC group at the first week of life. Regarding alpha and beta diversity, time was a key factor in the oral modulation of both groups, showing how dynamic this environment is in early life.
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8.
Macronutrient Sensing in the Oral Cavity and Gastrointestinal Tract: Alimentary Tastes.
Keast, R, Costanzo, A, Hartley, I
Nutrients. 2021;(2)
Abstract
There are numerous and diverse factors enabling the overconsumption of foods, with the sense of taste being one of these factors. There are four well established basic tastes: sweet, sour, salty, and bitter; all with perceptual independence, salience, and hedonic responses to encourage or discourage consumption. More recently, additional tastes have been added to the basic taste list including umami and fat, but they lack the perceptual independence and salience of the basics. There is also emerging evidence of taste responses to kokumi and carbohydrate. One interesting aspect is the link with the new and emerging tastes to macronutrients, with each macronutrient having two distinct perceptual qualities that, perhaps in combination, provide a holistic perception for each macronutrient: fat has fat taste and mouthfeel; protein has umami and kokumi; carbohydrate has sweet and carbohydrate tastes. These new tastes can be sensed in the oral cavity, but they have more influence post- than pre-ingestion. Umami, fat, kokumi, and carbohydrate tastes have been suggested as an independent category named alimentary. This narrative review will present and discuss evidence for macronutrient sensing throughout the alimentary canal and evidence of how each of the alimentary tastes may influence the consumption of foods.
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9.
A Log Ratio-Based Analysis of Individual Changes in the Composition of the Oral Microbiota in Different Dietary Phases.
Vach, K, Al-Ahmad, A, Anderson, A, Woelber, JP, Karygianni, L, Wittmer, A, Hellwig, E
Nutrients. 2021;(3)
Abstract
BACKGROUND Investigating the influence of nutrition on oral health has a long scientific history. Due to recent technical advances like sequencing techniques for the oral microbiota, this topic has gained scientific interest again. A basic challenge is to understand the influence of nutrition on the oral microbiota and on the interaction between the oral bacteria, which is also statistically challenging. METHODS Log-transformed ratios of two bacteria concentrations are introduced as the basic analytic tool. The framework is illustrated by application in an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. RESULTS The method could be sufficiently used to analyse the interrelation between the bacteria and to identify some bacterial groups with the same as well as different reactions to additional dietary components. It was found that the strongest changes in bacterial concentrations were achieved by the additional consumption of dairy products. CONCLUSION A log ratio-based analysis offers insights into the relation of different bacteria while taking specific features of compositional data into account. The presented methods allow becoming independent of the behaviour of other bacteria, which is a disadvantage of common analysis methods of compositions. The results indicate that modulations of the oral biofilm microbiota due to nutrition change can be attained.
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10.
Interplay between Dietary Polyphenols and Oral and Gut Microbiota in the Development of Colorectal Cancer.
Cueva, C, Silva, M, Pinillos, I, Bartolomé, B, Moreno-Arribas, MV
Nutrients. 2020;(3)
Abstract
Colorectal cancer (CRC) is the third most diagnosed type of cancer worldwide. Dietary features play an important role in its development, and the involvement of human microbial communities in this pathology has also recently been recognized. Individuals with CRC display alterations in gut bacterial composition and a notably higher abundance of putative oral bacteria in colonic tumors. Many experimental studies and preclinical evidence propose that dietary polyphenols have a relevant role in CRC development and progression, mainly attributed to their immunomodulatory activities. Furthermore, polyphenols can modulate oral and gut microbiota, and in turn, intestinal microbes catabolize polyphenols to release metabolites that are often more active and better absorbed than the original phenolic compounds. The current study aimed to review and summarize current knowledge on the role of microbiota and the interactions between dietary polyphenols and microbiota in relation to CRC development. We have highlighted the mechanisms by which dietary polyphenols and/or their microbial metabolites exert their action on the pathogenesis and prevention of CRC as modulators of the composition and/or activity of oral and intestinal microbiota, including novel screening biomarkers and possible nutritional therapeutic implications.