Mild heat stress promotes the differentiation of odontoblast-like MDPC-23 cells via yes-associated protein.

PURPOSE: Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing tertiary dentinogenesis and ensuring sustained therapeutic efficacy against DH. This study examined the effects and mechanism of action of mild heat stress (MHS) on the differentiation of odontoblast-like MDPC-23 cells. METHODS: We used a heating device to accurately control the temperature and duration, mimicking the thermal microenvironment of odontoblast-like cells. Using this device, the effects of MHS on cell viability and differentiation were examined. Cell viability was assessed using the MTT assay. The expression and nucleoplasmic ratio of the yes-associated protein (YAP) were examined by western blotting and immunofluorescence. The gene expression levels of heat shock proteins (HSPs) and dentin matrix protein-1 (DMP1) were measured using qPCR. Dentin sialophosphoprotein (DSPP) expression was evaluated using immunofluorescence and immunoblotting. Verteporfin was used to inhibit YAP activity. RESULTS: Mild heat stress (MHS) enhanced the odontoblast differentiation of MDPC-23 cells while maintaining cell viability. MHS also increased YAP activity, as well as the levels of HSP25 mRNA, HSP70 mRNA, HSP90α mRNA, DMP1 mRNA, and DSPP protein. However, after YAP inhibition, both cell viability and the levels of HSP90α mRNA, DMP1 mRNA, and DSPP protein were reduced. CONCLUSION: YAP plays a crucial role in maintaining cell viability and promoting odontoblast differentiation of MDPC-23 cells under MHS. Consequently, MHS is a potential therapeutic strategy for DH, and boosting YAP activity could be beneficial for maintaining cell viability and promoting odontoblast differentiation.

Dual Drug-Loaded Nanoliposomes Encapsulating Curcumin and 5-Fluorouracil with Advanced Medicinal Applications: Self-Monitoring and Antitumor Therapy.

Due to the presence of physiological barriers, it is difficult to achieve the desired therapeutic efficacy of drugs; thus, it is necessary to develop an efficient drug delivery system that enables advanced functions such as self-monitoring. Curcumin (CUR) is a naturally functional polyphenol whose effectiveness is limited by poor solubility and low bioavailability, and its natural fluorescent properties are often overlooked. Therefore, we aimed to improve the antitumor activity and drug uptake monitoring by simultaneously delivering CUR and 5-Fluorouracil (5-FU) in the form of liposomes. In this study, dual drug-loaded liposomes (FC-DP-Lip) encapsulating CUR and 5-FU were prepared by the thin-film hydration method; their physicochemical properties were characterized; and their biosafety, drug uptake distribution in vivo, and tumor cell toxicity were evaluated. The results showed that the nanoliposome FC-DP-Lip showed good morphology, stability, and drug encapsulation efficiency. It showed good biocompatibility, with no side effects on zebrafish embryonic development. In vivo uptake in zebrafish showed that FC-DP-Lip has a long circulation time and presents gastrointestinal accumulation. In addition, FC-DP-Lip was cytotoxic against a variety of cancer cells. This work showed that FC-DP-Lip nanoliposomes can enhance the toxicity of 5-FU to cancer cells, demonstrating safety and efficiency, and enabling real-time self-monitoring functions.

A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study.

BACKGROUND: The tRNA-derived small RNAs (tsRNAs) are produced in a nuclease-dependent manner in responses to variety of stresses that are common in cancers. We focus on a cancer-enriched tsRNA signature to develop a salivary exosome-based non-invasive biomarker for human esophageal squamous cell carcinoma (ESCC). METHODS: Cancer-enriched small RNAs were identified by RNA sequencing of salivary exosomes obtained from ESCC patients (n = 3) and healthy controls (n = 3) in a pilot study and further validated in discovery cohort (n = 66). A multicenter prospective observational study was conducted in two ESCC high-incidence regions (n = 320 and 200, respectively) using the newly developed biomarker signature. RESULTS: The tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes of ESCC patients, ESCC tissues and ESCC cells. The bi-signature composed of these small RNAs was able to discriminate ESCC patients from the controls with high sensitivity (90.50%) and specificity (94.20%). Based on the bi-signature Risk Score for Prognosis (RSP), patients with high-RSP have both shorter overall survival (OS) (HR 4.95, 95%CI 2.90-8.46) and progression-free survival (PFS) (HR 3.69, 95%CI 2.24-6.10) than those with low-RSP. In addition, adjuvant therapy improved OS (HR 0.47, 95%CI 0.29-0.77) and PFS (HR 0.36, 95%CI 0.21-0.62) only for patients with high but not low RSP. These findings are consistent in both training and validation cohort. CONCLUSIONS: The tsRNA-based signature not only has the potential for diagnosis and prognosis but also may serve as a pre-operative biomarker to select patients who would benefit from adjuvant therapy. TRIAL REGISTRATION: A prospective study of diagnosis biomarkers of esophageal squamous cell carcinoma, ChiCTR2000031507 . Registered 3 April 2016 - Retrospectively registered.

A novel strategy combining Mini-CEX and OSCE to assess standardized training of professional postgraduates in department of prosthodontics.

OBJECTIVE: Mini clinical evaluation exercise (mini-CEX) and objective structured clinical examination (OSCE) are widely acknowledged as effective measures of resident standardization training (RST) in European and American countries. However, in China primary mini-CEX and OSCE forms are mainly limited in undergraduate clinical examination. Little knowledge is available regarding the validity and right way of mini-CEX /OSCE evaluation system in advanced dental clinical education so far. This study aimed to explore whether combination of mini-CEX and OSCE represents a global-dimension assessment for postgraduate clinical competence in RST. METHODS: Postgraduates who received RST from June 2017 to June 2019 were selected and evaluated by modified mini-CEX/OSCE scales. Each student received evaluations at least twice in the initial and final stages of training (tested every 4 months). A questionnaire was conducted to investigate the satisfaction with the arrangement of RST. RESULTS: Mini-CEX/OSCE test results indicated that postgraduates have significantly improved their comprehensive competence in RST projects in the department of prosthodontics (P < 0.05). Compared to other master of Stomatology students, postgraduates taking up prosthodontics master's degree have made more progresses through a training period of up to 1 year and four sessions of face-to-face feedback tutoring (P < 0.05). Survey results revealed high level of satisfaction on clinical practice evaluation. CONCLUSION: Modified mini-CEX/OSCE combined evaluation system is an effective and reliable assessment tool for clinical comprehensive ability in the RST of professional graduates and can fully highlight their respective advantages on the improvement of students' clinical competency, especially after several rounds of assessments.

Nano-Liposomes Double Loaded with Curcumin and Tetrandrine: Preparation, Characterization, Hepatotoxicity and Anti-Tumor Effects.

(1) Background: Curcumin (CUR) and tetrandrine (TET) are natural compounds with various bioactivities, but have problems with low solubility, stability, and absorption rate, resulting in low bioavailability, and limited applications in food, medicine, and other fields. It is very important to improve the solubility while maintaining the high activity of drugs. Liposomes are micro-vesicles synthesized from cholesterol and lecithin. With high biocompatibility and biodegradability, liposomes can significantly improve drug solubility, efficacy, and bioavailability. (2) Methods: In this work, CUR and TET were encapsulated with nano-liposomes and g DSPE-MPEG 2000 (DP)was added as a stabilizer to achieve better physicochemical properties, biosafety, and anti-tumor effects. (3) Results: The nano-liposome (CT-DP-Lip) showed stable particle size (under 100 nm) under different conditions, high solubility, drug encapsulation efficiency (EE), loading capacity (LC), release rate in vitro, and stability. In addition, in vivo studies demonstrated CT-DP-Lip had no significant toxicity on zebrafish. Tumor cytotoxicity test showed that CT-DP-Lip had a strong inhibitory effect on a variety of cancer cells. (4) Conclusions: This work showed that nano-liposomes can significantly improve the physical and chemical properties of CUR and TET and make them safer and more efficient.

The colossal role of H-MnO2-PEG in ischemic stroke.

Stroke is one of the most serious problems that seriously affect people's health and brings huge economic burden to society. The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In recent years, nano drug delivery system has developed rapidly and applied to treat ischemic stroke. Here, we report the synthesis and functionalization of monodisperse hollow structured MnO2 (H-MnO2). The highly monodisperse H-MnO2 with uniform morphology was obtained by in situ growing MnO2 on solid silica nanoparticles and subsequently removing the silica core. After successive modification of poly ethylene glycol(PEG), we further verified their protective effect on ischemic stroke in our study.

Directional axonal regrowth induced by an aligned fibrin nanofiber hydrogel contributes to improved motor function recovery in canine L2 spinal cord injury.

Spinal cord injuries (SCI) normally disrupt the long axonal tracts of the spinal cord and cause permanent neurological deficits, for which there is currently a lack of effective therapeutic methods. Biomaterial-based regenerative medicine is a pivotal strategy to induce axonal regeneration through delivery of biophysical and/or biochemical regulatory cues by biomaterials. We previously fabricated a hierarchically aligned fibrin hydrogel (AFG) that could promote neurogenic differentiation of stem cells in vitro and has been successfully applied for peripheral nerve and spinal cord regeneration in rats. In this study, AFG was used to repair a canine lumbar segment 2 hemisection spinal cord injury, and the consistency of histological, imageological and behavioral results was compared. AFG was used to construct an aligned fiber bridge that supported cell adhesion in vitro and rapidly facilitated tissue invasion along the long axis of fibers in vivo, Moreover, in vivo results demonstrated regrowth of axons in an oriented pattern connecting the rostral and caudal stumps. Consistent results were confirmed by diffusion tensor imaging, which allowed successful tracing of reconnected nerve fibers across the defect. As a result, directional axonal regrowth contributed to significantly improved recovery of motor functional behavior of SCI canines with AFG implantation. Our results suggest that AFG has great promise for rapidly directing axonal regrowth for nerve regeneration.

A competitive immunoassay based on engineered magnetic/fluorescent nanoparticles and biolayer interferometry-based assay for T-2 toxin determination.

For the first time a competitive immunoassay was developed by employing T-2 antibody-functionalized magnetite nanoparticles and T-2 toxin-conjugated fluorescent quantum dots (QDs). Free T-2 and the T-2-modified QDs compete for binding to antibody-modified magnetic beads; the magnetic beads collected by magnetic separation were subjected to fluorescence intensity analysis (with excitation/emission wavelengths at 460/616 nm). This competitive immunoassay for T-2 toxin determination was applied both in a microcentrifuge tube and on a 96-well plate. The dynamic range of the immunoassay is 1-100 ng mL-1, the limit of detection (LOD) is 0.1 ng mL-1, and determination was completed in about 40 min and 30 min in the microcentrifuge tube and 96-well plate, respectively. Moreover, the biolayer interferometry (BLI) technique was employed for T-2 determination for the first time, in which the conjugate of T-2 toxin and bovine serum albumin (BSA) was immobilized on the sensors before detection. Its average recovery of T-2 toxin from barley sample ranged from 82.00 to 123.33%, and the relative standard deviation (RSD) was between 9.42 and 15.73%. The LOD of the BLI-based assay is 5 ng mL-1, and it only takes 10 min to finish the determination. Graphical abstract.

Assessing the Quality of Mobile Exercise Apps Based on the American College of Sports Medicine Guidelines: A Reliable and Valid Scoring Instrument.

BACKGROUND: Regular physical activity can not only help with weight management, but also lower cardiovascular risks, cancer rates, and chronic disease burden. Yet, only approximately 20% of Americans currently meet the physical activity guidelines recommended by the US Department of Health and Human Services. With the rapid development of mobile technologies, mobile apps have the potential to improve participation rates in exercise programs, particularly if they are evidence-based and are of sufficient content quality. OBJECTIVE: The goal of this study was to develop and test an instrument, which was designed to score the content quality of exercise program apps with respect to the exercise guidelines set forth by the American College of Sports Medicine (ACSM). METHODS: We conducted two focus groups (N=14) to elicit input for developing a preliminary 27-item scoring instruments based on the ACSM exercise prescription guidelines. Three reviewers who were no sports medicine experts independently scored 28 exercise program apps using the instrument. Inter- and intra-rater reliability was assessed among the 3 reviewers. An expert reviewer, a Fellow of the ACSM, also scored the 28 apps to create criterion scores. Criterion validity was assessed by comparing nonexpert reviewers' scores to the criterion scores. RESULTS: Overall, inter- and intra-rater reliability was high with most coefficients being greater than .7. Inter-rater reliability coefficients ranged from .59 to .99, and intra-rater reliability coefficients ranged from .47 to 1.00. All reliability coefficients were statistically significant. Criterion validity was found to be excellent, with the weighted kappa statistics ranging from .67 to .99, indicating a substantial agreement between the scores of expert and nonexpert reviewers. Finally, all apps scored poorly against the ACSM exercise prescription guidelines. None of the apps received a score greater than 35, out of a possible maximal score of 70. CONCLUSIONS: We have developed and presented valid and reliable scoring instruments for exercise program apps. Our instrument may be useful for consumers and health care providers who are looking for apps that provide safe, progressive general exercise programs for health and fitness.

Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study.

The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild-moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm-2) compared with both severe asthma groups (SAn: 17.4 mm-2, p<0.001; SAs/ex: 22.2 mm-2, p=0.01) and with the MMA group (21.2 mm-2, p=0.01). The number of CD4+ lymphocytes was decreased in the SAs/ex group (4.7 mm-2) compared with the SAn (11.6 mm-2, p=0.002), MMA (10.1 mm-2, p=0.008) and HC (10.6 mm-2, p<0.001) groups. No other differences were observed.Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall.

Use of Computer-Assisted Navigation in the Retrieval of Accidentally Displaced Third Molars.

PURPOSE: The purpose of this study was to describe the application of computer-assisted navigation for the retrieval of accidentally displaced mandibular third molars. PATIENTS AND METHODS: All patients identified as having an accidentally displaced mandibular third molar or root fragment and presented to the authors' department from April 2013 through June 2015 were included in this prospective study. Retrieval of the displaced molar was performed in these patients under the guidance of computer-assisted navigation, in which a registered forceps was used to clamp and retrieve the molar. Postoperative complications were assessed for all patients. RESULTS: Twelve patients were included in this case series. Using computer-assisted navigation, the operation proceeded successfully in all patients. These patients displayed uneventful healing without postoperative complications. CONCLUSION: Computer-assisted navigation is a safe, straightforward, and minimally invasive treatment method that can be applied for the retrieval of accidentally displaced third molars. It is recommended as an intraoperative tool for the retrieval of teeth or tooth fragments displaced into areas that are difficult to access.

Human cathelicidin LL-37 enhance the antibiofilm effect of EGCG on Streptococcus mutans.

BACKGROUND: Streptococcus mutans forms biofilms as a resistance mechanism against antimicrobial agents in the human oral cavity. We recently showed that human cathelicidin LL-37 exhibits inhibitory effects on biofilm formation of S. mutans through interaction with lipoteichoic acid (LTA), but without antibacterial or biofilm dispersal abilities. (-)-Epigallocatechin gallate (EGCG) is the most abundant constituent of tea catechins that has the greatest anti-infective potential to inhibit the growth of various microorganisms and biofilm formation. Therefore, in this study, we evaluated whether LL-37 interacts with EGCG to enhance the antibiofilm effect of EGCG on S. mutans biofilm formation. METHODS: Clinical S. mutans strains (n = 10) isolated from children's saliva were tested in a biofilm formation assay. The antibiofilm effect of EGCG with and without LL-37 was analyzed by the minimum biofilm eradication concentration assay and confirmed using field emission-scanning electron microscopy. In addition, the interaction among EGCG, LL-37, and LTA of S. mutans was determined using quartz crystal microbalance analysis. RESULTS: EGCG killed 100 % of planktonic S. mutans within 5 h, inhibited biofilm formation within 24 h, and reduced bacteria cells in preformed biofilms within 3 h at a concentration of 0.2 mg/mL. However, EGCG did not appear to interact with LTA. LL-37 effectively enhanced the bactericidal activity of EGCG against biofilm formation and preformed biofilms as determined by quantitative crystal violet staining and field emission-scanning electron microscopy. In addition, quartz crystal microbalance analysis revealed that LL-37 interacted with EGCG and promoted binding between EGCG and LTA of S. mutans. CONCLUSIONS: We show that LL-37 enhances the antibiofilm effect of EGCG on S. mutans. This finding provides new knowledge for dental treatment by using LL-37 as a potential antibiofilm compound.

The stability and controlled release of I-ascorbic acid encapsulated in poly (ethyl-2-cyanoacrylate) nanocapsules prepared by interfacial polymerization of water-in-oil microemulsions.

The L-ascorbic acid (AA) was encapsulated into biodegradable and biocompatible poly(ethyl-2-cyanoacrylate) (PECA) nanocapsules by interfacial polymerization of water-in-oil (W/O) microemulsions. The influences of surfactant concentration, pH value of the dispersed aqueous phase, and W/O ratio on nanocapsule size were discussed. The stability and in vitro release of encapsulated AA were also investigated. The results show that nanocapsules could be obtained under the conditions with low pH value, high fraction of aqueous phase, and appropriate surfactant concentration. The encapsulated AA was protected by nanocapsules from oxidation and presented superior storage stability in aqueous medium than pure AA. Releasing AA from the inner core of nanocapsules could be controlled by adjusting the enzyme hydrolysis extent of the PECA wall.

Health literacy: a pathway to better oral health.

OBJECTIVES: We examined whether health literacy was associated with self-rated oral health status and whether the relationship was mediated by patient-dentist communication and dental care patterns. METHODS: We tested a path model with data collected from 2 waves of telephone surveys (baseline, 2009-2010; follow-up, 2011) of individuals residing in 36 rural census tracts in northern Florida (final sample size n = 1799). RESULTS: Higher levels of health literacy were associated with better self-rated oral health status (B = 0.091; P < .001). In addition, higher levels of health literacy were associated with better patient-dentist communication, which in turn corresponded with patterns of regular dental care and better self-rated oral health (B = 0.003; P = .01). CONCLUSIONS: Our study showed that, beyond the often-reported effects of gender, race, education, financial status, and access to dental care, it is also important to consider the influence of health literacy and quality of patient-dentist communication on oral health status. Improved patient-dentist communication is needed as an initial step in improving the population's oral health.

[Selecting solvent and solubilizer for puerarin nasal drops by solubility and irritation].

In order to test the equilibrium solubility of puerarin in different solvents and solubilizer,cilia toxicity and irritation of these excipient, the balance method, toad in the ciliary body toxicity and rat nasal mucosa irritation were used respectively. Results showed that puerarin solubility was 56.44 g x L(-1) in combined solvent of 30% PEG200 and 10% Kolliphor HS 15. With normal saline solution as negative control and sodium deoxycholate as positive control, the effects of 30% PEG200, 30% PEG 400, 10% Kolliphor HS 15 and combination of 30% of PEG200 and 10% Kolliphor HS 15 on toad palate cilium were observed and cilia movement duration was recorded. The results indicated that there was no significant difference in cilia movement duration among 30% PEG200, 10% Kolliphor HS 15 and normal saline group. The rats long-term nasal mucous membrane irritation of 30% PEG 400, 10% Kolliphor HS 15, which had no cilia toxicity, was studied, with normal saline solution as negative control. There were no significant difference revealed on rat nasal mucosa epithelial thickness among 30% PEG 400, 10% Kolliphor HS 15 and normal saline. Above researches showed 30% PEG 400, 10% Kolliphor HS 15 was ideal for solubility of puerarin nasal drops and showed a lower cilia toxicity and irritation, and can be used as the solvent and solubilizer of puerarin nasal drops.

Highly stable Ag-doped Cu2O immobilized cellulose-derived carbon beads with enhanced visible-light photocatalytic degradation of levofloxacin.

Ag-doped Cu2O immobilized carbon beads (Ag/Cu2O@CB) based composite photocatalysts have been prepared for the removal of levofloxacin, an antibiotic, from water. The photocatalysts were prepared by the processes of chemical reduction and in-situ solid-phase precipitation. The composite photocatalyst was characterized by a porous and interconnected network structure. Ag nanoparticles were deposited on Cu2O particles to develop a metal-based semiconductor to increase the catalytic efficiency of the system and the separation efficiency of the photogenerated carriers. Cellulose-derived carbon beads (CBs) can also be used as electron storage libraries which can capture electrons released from the conduction band of Cu2O. The results revealed that the maximum catalytic degradation efficiency of the composite photocatalyst for the antibiotic levofloxacin was 99.02 %. The Langmuir-Hinshelwood model was used to study the reaction kinetics, and the process of photodegradation followed first-order kinetics. The maximum apparent rate was recorded to be 0.0906 min-1. The mass spectrometry technique showed that levofloxacin degraded into carbon dioxide and water in the presence of the photocatalyst. The results revealed that the easy-to-produce photocatalyst was stable and efficient in levofloxacin removing.

Piezo Mediates the Mechanosensation and Injury-Repair of Pulpo-Dentinal Complex.

OBJECTIVES: The aim of this research was to investigate the functions of Piezo channels in dentin defect, including mechanical signalling and odontoblast responses. METHODS: Rat dentin-defect models were constructed, and spatiotemporal expression of Piezo proteins was detected in the pulpo-dentinal complex. Real-time polymerase chain reaction (rtPCR) was used to investigate the functional expression pattern of Piezo channels in odontoblasts. Moreover, RNA interference technology was employed to uncover the underlying mechanisms of the Piezo-driven inflammatory response and repair under fluid shear stress (FSS) conditions in vitro. RESULTS: Piezo1 and Piezo2 were found to be widely expressed in the odontoblast layer and dental pulp in the rat dentin-defect model during the end stage of reparative dentin formation. The expression levels of the Piezo1 and Piezo2 genes in MDPC-23 cells were high in the initial stage under FSS loading and then decreased over time. Moreover, the expression trends of inflammatory, odontogenic, and mineralisation genes were generally contrary to those of Piezo1 and Piezo2 over time. After silencing of Piezo1/Piezo2, FSS stimulation resulted in significantly higher expression of inflammatory, odontogenesis, and mineralisation genes in MDPC-23 cells. Finally, the expression of genes involved in the integrin ß1/ERK1 and Wnt5b/ß-catenin signalling pathways was changed in response to RNA silencing of Piezo1 and Piezo2. CONCLUSIONS: Piezo1 and Piezo2 may be involved in regulating the expression of inflammatory and odontogenic genes in odontoblasts stimulated by FSS.

Association between periodontitis and endometriosis: a bidirectional Mendelian randomization study.

Introduction: A potential association between periodontitis and endometriosis has been indicated in previous observational studies. Nevertheless, the causal link between these two disorders has not been clarified. Methods: Based on publicly available genome-wide association study (GWAS) summary datasets, we conducted a bidirectional Mendelian randomization (MR) study to investigate the relationship between periodontitis and endometriosis and its subtypes. Single nucleotide polymorphisms (SNPs) strongly associated with candidate exposures at the genome-wide significance level (P < 5 × 10-8) were selected as instrumental variables (IVs). The inverse variance-weighted regression (IVW) was performed to estimate the causal effect of periodontitis on endometriosis. We further conducted two sensitivity analyses, MR-Egger and weighted median, to test the validity of our findings. The main results were replicated via data from the UK Biobank. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causality. Results: The IVW method suggested that periodontitis was positively associated with endometriosis of the pelvic peritoneum (OR = 1.079, 95% CI = 1.016 to 1.146, P = 0.014). No causal association was indicated between periodontitis and other subtypes of endometriosis. In reversed analyses, no causal association between endometriosis or its subtypes and periodontitis was found. Conclusions: Our study provided genetic evidence on the causal relationship between periodontitis and endometriosis of the pelvic peritoneum. More studies are necessary to explore the underlying mechanisms.

Assessing the association between tea intake and risk of dental caries and periodontitis: a two-sample Mendelian randomization study.

Tea is an indispensable beverage in people's daily life. However, the relationship between tea intake and dental caries and periodontitis is controversial. We extracted datasets for tea intake and oral diseases from genome-wide association studies (GWASs) conducted by the UK Biobank and the Gene Lifestyle Interactions in Dental Endpoints consortium. We selected 38 single-nucleotide polymorphisms (SNPs) significantly associated with tea intake as instrumental variables (IVs) (P < 5.0 × 10-8). Mendelian randomization (MR) was performed to investigate the potential causality between tea intake and caries and periodontitis. Multivariable Mendelian randomization (MVMR) analyses were utilized to estimate causal effects of tea intake on risk of caries and periodontitis after adjusting for smoking, body mass index (BMI), and socioeconomic factors. The results showed that higher tea intake was suggestively associated with fewer natural teeth (ß = - 0.203; 95% CI = 0.680 to 0.980; P = 0.029) and higher risk of periodontitis (OR = 1.622; 95% CI = 1.194 to 2.205; P = 0.002). After Bonferroni correction, the causality of tea intake on periodontitis remained significant. The significance of periodontitis disappeared after adjusting for the socioeconomic factors in MVMR (OR = 1.603; 95% CI = 0.964 to 2.666; P = 0.069). Tea intake had no association with risk of caries. Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study. Our results provide insight into the potential relationship between tea intake and oral diseases from a dietary lifestyle perspective, which may help prevent oral diseases.

Genetic Connectivity of Gut Microbiota and Oral Ulcers: A Mendelian Randomization Study.

OBJECTIVES: The aim of this study was to reveal the relationship, if any, between gut microbiota and oral ulcers. METHODS: We performed a 2-sample Mendelian randomization (MR) study to estimate the roles of gut microbiota in mouth ulcers. The summary datasets of gut microbiota were from the largest genome-wide association study (GWAS) conducted by MiBioGen, and data of mouth ulcers were obtained from UK Biobank. Random effect inverse variance-weighted, weighted median, MR Egger, simple mode and weighted mode were used to estimate the relationship. Sensitivity analyses were conducted to assess the heterogeneity and pleiotropy of instrumental variables. MR Steiger filtering was also applied to orient the causal direction. RESULTS: Three gut microbiota taxa were positively associated with mouth ulcers: Holdemania (odds ratio [OR] = 1.005, 95% confidence interval [CI]: 1.001-1.009, P = .019), Oxalobacter (OR = 1.004, 95% CI: 1.000-1.007, P = .032), and Ruminococcaceae UCG011 (OR = 1.006, 95% CI: 1.001-1.011, P = .029), while 4 gut microbiota taxa were negatively associated with mouth ulcers: Actinobacteria (OR = 0.992, 95% CI: 0.985-1.000, P = .042), Lactobacillales (OR = 0.995, 95% CI: 0.990-1.000, P = .034), Oscillospira (OR = 0.990, 95% CI: 0.984-0.997, P = .007) and Phascolarctobacterium (OR = 0.992, 95% CI: 0.986-0.997, P = .003). Sensitivity analyses validated the robustness of the association in between. CONCLUSIONS: This MR study identified a strong association between the quality of gut microbiota and oral ulcers. The findings are likely to expand the therapeutic targets for mouth ulcers.