LPS-induced inflammation potentiates dental pulp stem cell odontogenic differentiation through C5aR and p38.

AIM: Inflammation is a complex host response to harmful infection or injury, and it seems to play a crucial role in tissue regeneration both positively and negatively. We have previously demonstrated that the activation of the complement C5a pathway affects dentin-pulp regeneration. However, limited information is available to understand the role of the complement C5a system related to inflammation-mediated dentinogenesis. The aim of this study was to determine the role of complement C5a receptor (C5aR) in regulating lipopolysaccharide (LPS)-induced odontogenic differentiation of dental pulp stem cells (DPSCs). MATERIAL AND METHODS: Human DPSCs were subjected to LPS-stimulated odontogenic differentiation in dentinogenic media treated with the C5aR agonist and antagonist. A putative downstream pathway of the C5aR was examined using a p38 mitogen-activated protein kinase (p38) inhibitor (SB203580). RESULTS: Our data demonstrated that inflammation induced by the LPS treatment potentiated DPSC odontogenic differentiation and that this is C5aR dependent. C5aR signaling controlled the LPS-stimulated dentinogenesis by regulating the expression of odontogenic lineage markers like dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1). Moreover, the LPS treatment increased the total p38, and the active form of p38 expression, and treatment with SB203580 abolished the LPS-induced DSPP and DMP-1 increase. CONCLUSIONS: These data suggest a significant role of C5aR and its putative downstream molecule p38 in the LPS-induced odontogenic DPSCs differentiation. This study highlights the regulatory pathway of complement C5aR/p38 and a possible therapeutic approach for improving the efficiency of dentin regeneration during inflammation.

Performance evaluation of deep learning models for the classification and identification of dental implants.

STATEMENT OF PROBLEM: Dental implant systems can be identified using image classification deep learning. However, investigations on the accuracy of classifying and identifying implant design through an object detection model are lacking. PURPOSE: The purpose of this study was to evaluate the performance of an object detection deep learning model for classifying the implant designs of 103 types of implants. MATERIAL AND METHODS: From panoramic radiographs, 14 037 implant images were extracted. Implant designs were subdivided into 10 classes in the coronal, 13 in the middle, and 10 in the apical third. Classes with fewer than 50 images were excluded from the training dataset. Among the images, 80% were used as training data, and the remaining 20% as test data; the data were generated 3 times for 3-fold cross-validation (implant datasets 1, 2, and 3). Versions 5 and 7 of you only look once (YOLO) algorithm were used to train the model, and the mean average precision (mAP) was evaluated. Subsequently, data augmentation was performed using image processing and a real-enhanced super-resolution generative adversarial network, and the accuracy was re-evaluated using YOLOv7. RESULTS: The mAP of YOLOv7 in the 3 datasets was 0.931, 0.984, and 0.884, respectively, which were higher than the mAP of YOLOv5. After image processing in implant dataset-1, the mAP improved to 0.986 and, with the real-enhanced super-resolution generative adversarial network, to 0.988 and 0.986 at magnification ×2 and ×4, respectively. CONCLUSIONS: The object detection model for classifying implant designs found a high accuracy for 26 classes. The mAP of the model differed depending on the type of algorithm, image processing process, and detailed implant design.

Changing the topographical anatomy among the maxilla, palatine bone, and greater palatine nerve: a histological study using human fetuses.

PURPOSE: The palatine bone (PAL) rides over the maxilla (MX) without an end-to-end suture in the bony palate of fetuses. However, changes in the topographical relationship among bones was unknown at and along the pterygopalatomaxillary suture, including the palatine canals. METHODS: Using sagittal, frontal, and horizontal histological sections of the head from 15 midterm fetuses to 12 near-term fetuses, we depicted the changes in the topographical anatomy of the MX, PAL, and greater palatine nerve (GPN). RESULTS: In the bony greater palatine canal of these fetuses, the medial and posterior walls facing the GPN were consistently made up of the PAL. At midterm, the entire course of the GPN was embedded in the PAL (six fetuses), or the MX contributed to the lateral wall of the nerve canal (nine). At near-term, the anterior and lateral walls showed individual variations: an MX in the anterior and lateral walls (three fetuses), an anterior MX and a lateral PAL (five), an anterior PAL and a lateral MX (two), and a PAL surrounding the GPN (four). CONCLUSION: These increasing variations suggested that the pterygopalatomaxillary suture was actually growing and that the PAL transiently expanded anteriorly and/or laterally to push the MX in fetuses. The "usual" morphology in which the GPN is sandwiched by the MX and PAL is likely established after birth, possibly during adolescence. The driving force of this change may not be produced by the masticatory apparatus. Rather, it might be triggered by the growing maxillary sinus.

C5a complement receptor modulates odontogenic dental pulp stem cell differentiation under hypoxia.

AIM: Alterations in the microenvironment change the phenotypes of dental pulp stem cells (DPSCs). The role of complement component C5a in the differentiation of DPSCs is unknown, especially under oxygen-deprived conditions. The aim of this study was to determine the effect of C5a on the odontogenic differentiation of DPSCs under normoxia and hypoxia. MATERIAL AND METHODS: Human DPSCs were subjected to odontogenic differentiation in osteogenic media and treated with the C5a receptor antagonist-W54011 under normal and hypoxic conditions (2% oxygen). Immunochemistry, western blot, and PCR analysis for the various odontogenic differentiation genes/proteins were performed. RESULTS: Our results demonstrated that C5a plays a positive role in the odontogenic differentiation of DPSCs. C5a receptor inhibition resulted in a significant decrease in odontogenic differentiation genes, such as DMP1, ON, RUNX2, DSPP compared with the control. This observation was further supported by the Western blot data for DSPP and DMP1 and immunohistochemical analysis. The hypoxic condition reversed this effect. CONCLUSIONS: Our results demonstrate that C5a regulates the odontogenic DPSC differentiation under normoxia. Under hypoxia, C5a exerts a reversed function for DPSC differentiation. Taken together, we identified that C5a and oxygen levels are key initial signals during pulp inflammation to control the odontogenic differentiation of DPSCs, thereby, providing a mechanism for potential therapeutic interventions for dentin repair and vital tooth preservation.

Randomized trial of oral sulfate solution versus polyethylene glycol-ascorbic acid for bowel cleansing in elderly people.

BACKGROUND AND AIM: The efficacy and safety of the recently introduced low-volume purgatives in elderly people are not well known. Therefore, in this trial, we aimed to evaluate and compare the efficacy of two low-volume agents, oral sulfate solution (OSS) and 2-L polyethylene glycol with ascorbic acid (PEG-Asc), in elderly people. METHODS: A prospective, randomized, single-blinded, multicenter, non-inferiority trial was performed at three university-affiliated hospitals in South Korea. Outpatients aged 65-80 years, who underwent elective colonoscopy, were enrolled. The primary outcome was the rate of adequate bowel preparation assessed using the Boston Bowel Preparation Scale. RESULTS: A total of 199 subjects were randomized into the OSS (n = 99) or the 2-L PEG-Asc (n = 100) group. Of them, 189 subjects were included in the analysis of the primary outcome (OSS group 95 vs PEG-Asc group 94). The proportion of adequate bowel preparation was 89.5% (85/95) in the OSS group and 93.6% (88/94) in the 2-L PEG-Asc group. OSS was not inferior to 2-L PEG-Asc according to the prespecified non-inferiority margin of -15% (95% confidence interval for the difference, -12.1 to 3.8). Vomiting (11.6% vs 2.1%) and thirst (24.2% vs 11.7%) were more common in the OSS group than in the 2-L PEG-Asc group. CONCLUSIONS: OSS is an effective low-volume purgative that is non-inferior to 2-L PEG-Asc in elderly people. Both the low-volume agents were identified to be well tolerated and safe in the healthy elderly population.

The incudopetrosal joint of the human middle ear: a transient morphology in fetuses.

In spite of the amount of research on fetal development of the human middle ear and ear ossicles, there has been no report showing a joint between the short limb of incus and the otic capsule or petrous part of the temporal bone. According to observations of serial histological sections from 65 embryos and fetuses at 7-17 weeks of development, the incudopetrosal joint exhibited a developmental sequence similar to the other joints of ossicles, with an appearance of an interzone followed by a trilaminar configuration at 7-12 weeks, a joint cavitation at 13-15 weeks and development of intraarticular and capsular ligaments at 16-17 weeks. These processes occurred at the same time or slightly later than any other joint. Thus, the joint development might coordinate with vibrating ossicles in utero. The growing short limb of incus appeared to accelerate an expansion of the epitympanic recess of the tympanic cavity. Additional observations of five late-stage fetuses demonstrated the incudopetrosal joint located in the fossa incudis joint changing to syndesmosis. Consequently, a real joint with a cavity existed transiently between the human neurocranium and the first pharyngeal arch derivative (i.e. incus) in contrast to the tympanostapedial joint or syndesmosis between the neurocranium and the second arch derivative. The newly described joint might have an effect on the widely accepted primary jaw concept: the mammalian jaw should thus have been created within the first pharyngeal arch, although the connection with neurocranium by the stapes is of a different origin.

Biocompatibility Evaluation of Feldspathic Porcelain with Nano-Sized Silver Ion Particles.

The major failure of dental restorations is caused by dental caries by S. mutans. This study evaluated the effect of nanosized silver ions in feldspathic porcelain on cytotoxicity and antimicrobial activity. The control group was feldspathic porcelain (Noritake EX-3, Kuraray Noritake Dental Inc., Japan) that did not contain Ag (silver). The experimental groups were feldspathic porcelain mixed with colloidal solutions of nanosized silver ions in mixtures of 5% 10%, 20%, 30%. Cell activity assays evaluated with osteoblast hFOB 1.19 cells (human Fetal Osteoblastic cell line, ATCC® CRL- 11372™) and antimicrobial activity test used the streptococcus mutans (S. mutans). According to the observations, the addition of Ag to feldspathic porcelain led to increased cell activity and showed excellent antibacterial performance. Especially, the feldspathic porcelain with 30% nanosized Ag ion appeared to have a significant antimicrobial effect, this allows for the possibility of various clinical applications for such material, including use in dental prosthesis and implants.

Effect on Adhesion of Porphyromonas gingivalis by Titanium Nitride Sputter Coating or Plasma Nitriding of Titanium.

Porphyromonas gingivalis (P. gingivalis) is one of main bacteria that adheres to the surface of dental implants and causes peri-implantitis. The purpose of this study was to observe the surface characteristics of titanium processed with either titanium nitride (TiN) sputter coating or plasma nitriding and to evaluate the subsequent adhesion of P. gingivalis. Specimens were divided into three groups: commercially pure (CP) titanium (control group), TiN sputter­coated titanium (group S), and plasma-nitrided titanium (group P). Surface characteristics such as roughness, morphology, and the formation of a thin TiN film or a nitriding layer were assessed. Adhesion of P. gingivalis in the three groups was determined by means of the crystal violet staining assay, and results were compared with one-way ANOVA, with post hoc comparison using Tukey's test (α = 0.05). Surface roughness values for the control group, group S, and group P were 0.08±0.02 µm, 0.19±0.04 µm, and 0.13±0.02 µm, respectively. In group S, the TiN layer was 1.36±0.1 µm thick, and nitrogen was detected on the surface of the specimens in group P, confirming formation of a nitrided layer. The level of adhesion in group P was significantly higher than that in the control group and in group S (p < 0.05), but there was no significant difference between the control group and group S. Within the limitations of this study, TiN sputter coating did not affect adhesion of P. gingivalis on the titanium surface, whereas adhesion was increased on the plasma-nitrided titanium surface.

Surface Characteristics of Bioactive Glass-Infiltrated Zirconia with Different Hydrofluoric Acid Etching Conditions.

The purpose of this study was to examine the surface characteristics of bioactive glass-infiltrated zirconia specimens that underwent different hydrofluoric acid (HF) etching conditions. Specimens were classified into the following six groups: Zirconia, Zirliner, Porcelain, Bioactive glass A1, Bioactive glass A2, and Bioactive glass A3. Zirliner and porcelain were applied to fully sintered zirconia followed by heat treatment. Bioactive glass was infiltrated into presintered zirconia using a spin coating method followed by complete sintering. All the specimens were acid-etched with 10% or 20% HF, and surface roughness was measured using a profiler. The surface roughness of the zirconia group was not affected by the etching time or the concentration of the acid. The roughness of the three bioactive glass groups (A1, A2, and A3) was slightly increased up until 10 minutes of etching. After 1 hour of etching, the roughness was considerably increased. The infiltrated bioactive glass and acid etching did not affect the adhesion and proliferation of osteoblasts. This study confirmed that surface roughness was affected by the infiltration material, etching time, and acid concentration. For implant surfaces, it is expected that the use of etched bioactive glass-infiltrated zirconia with micro-topographies will be similar to that of machined or sand-blasted/acid-etched (SLA) titanium.

Predictive Value of Dental Maturity for a Positive Gonadotropin-Releasing Hormone Stimulation Test Result in Girls with Precocious Puberty.

Dental maturity is associated with skeletal maturity, which is advanced in girls with central precocious puberty (CPP). We investigated the performance of dental maturity as a screening method for CPP using mandibular second premolar and molar calcification stages, assessed the associated anthropometric and laboratory factors, and evaluated pubertal response predictors using the gonadotropin-releasing hormone stimulation test (GnRHST) in prepubertal and pubertal girls. A prospective case-control study was conducted in girls, aged 7.0-8.9 years, classified into pubertal (peak luteinizing hormone [LH] after GnRHST ≥ 5 IU/L), prepubertal (peak LH < 5 IU/L), and control groups. Auxological and biochemical tests, panoramic radiographs, and GnRHSTs in participants with breast development were conducted. Dental maturity was assessed using the Demirjian index (DI). We included 103 girls (pubertal, 40; prepubertal, 19; control, 44). Chronological age (CA) was not significantly different between groups. Bone age (BA) and BA advancement was higher in the pubertal and prepubertal groups. Increased DI values at the mandibular second premolar and molar were significantly associated with CA, BA, BA advancement, height standard deviation score (SDS), peak LH after GnRHST, and insulin-like growth factor-I (IGF-I) (all P < 0.05). Moreover, odds ratio (OR) of the mandibular second premolar and molar (a DI value of ≥ E) for predicting a positive response to GnRHST was 8.7 (95% confidence intervals [CI], 2.9-26.1) and 5.2 (95% CI, 2.2-12.7), respectively. Dental maturity was a strong predictor for diagnosing CPP. Determining dental maturity in girls with suspected precocious puberty might help determine the performance of GnRHSTs.

Fetal Development of Human Oral Epithelial Pearls With Special Reference to Their Stage-Dependent Changes in Distribution.

OBJECTIVE: To access detailed distribution and age-dependent changes of oral epithelial pearls. DESIGN: Investigation and analysis with human fetal serial sections. SETTING: Institute of Embryology. METHODS: This study examined serial frontal sections of the upper and lower jaws of 19 human fetuses at 12 to 18 weeks and of the lower jaws of four late-stage fetuses. RESULTS: The upper jaw contained more than 20 midline and more than 60 lateral pearls greater than 20 µm in diameter, whereas the lower jaw contained fewer than 30 pearls of the same size. Midline pearls in the upper jaw were often cylindrical or rugby-ball shaped, whereas all pearls in the lower jaw were small and spherical. Epithelial pearls in the upper jaw started developing along the upper midline until 12 weeks; lateral pearls and additional midline pearls (or strictly, paramedian pearls) developed until 15 weeks. In the lower jaw, however, pearl development started at 18 weeks and was almost always from the dental lamina. Some of the fetuses assessed had an open nasopalatine canal without a duct, but there was no fibrous connection between this canal and pearls. Similarly, the lip frenulum or incisive suture was not connected with these pearls. CONCLUSION: The timing and sequence of development suggest that postfusion rupture of the palate by midline pearls was unlikely.

DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies.

Distraction osteogenesis and orthognathic surgery for a patient with unilateral cleft lip and palate.

Maxillary deficiency is a common feature in patients with repaired cleft lip and palate. Orthognathic surgery has been the conventional approach for the management of cleft-related maxillary hypoplasia. However, for patients with a severe maxillary deficiency, orthognathic surgery alone has many disadvantages, such as high relapse rates of 25% to 40%, instability, limited amount of advancement, and a highly invasive surgical technique. As an alternative treatment method, distraction osteogenesis has been used successfully in the distraction of the mandible, the maxilla, the entire midface, and the orbits as well as the cranial bones, with stable outcomes. The type of distraction device, either external or internal, can be chosen based on the surgical goals set for the patient. In this study, we report on the use of a rigid external distraction device for maxillary advancement in a 22-year-old woman with a repaired unilateral cleft lip and palate and severe maxillary hypoplasia. After the distraction osteogenesis, 2-jaw surgery was performed to correct the maxillary yaw deviation and the mandibular prognathism.

Analysis of parabens in dentifrices and the oral cavity.

This study analyzed levels of parabens in commercial dentifrices and saliva. HPLC was performed using 35% acetonitrile and measuring absorbance at 254 nm. Thirteen toothpastes and five mouthwashes were analyzed. Of these, volunteers used three toothpastes and two mouthwashes, and levels of parabens were analyzed in saliva and water used for mouth rinsing. In toothpastes, the highest concentrations of methylparaben (MP), propylparaben (PP) and n-butylparaben (nBP) were 1.86, 1.42 and 1.87 mg/g, respectively. In mouthwashes, the highest concentrations of MP and PP were 0.97 and 0.11 mg/mL, respectively. After volunteers used 500 mg toothpaste T-1, which contained 895 µg MP, the first and tenth mouth rinse samples contained means of 64.63 and 1.89 µg MP, respectively. After rinsing the mouth three or five times, 37 µg or 18 µg MP was calculated to remain in the oral cavity, respectively. After using 20 mL mouthwash S-1, which contained 19 mg MP, 1.53 mg MP was calculated to remain in the oral cavity. Immediately after using this mouthwash, the mean salivary concentration of MP was 237 µg/mL. The daily intake of parabens from dentifrices was predicted to be insignificant compared with the intake from food; however, parabens can be ingested from dentifrices.

Striated muscle fiber crossings of the head and neck: a histological study using near-term human fetuses and elderly cadavers.

Striated muscle fiber crossings at almost right angle are known to exist in the face, soft palate, pharyngeal wall and tongue. We aimed to identify a specific interface tissue at the crossing. We observed histological sections from 22 half-heads of 12 near-term fetuses at 26-40 weeks (crown-rump length, 215-334 mm). For comparison, we also observed tongue frontal sections from 5 elderly cadavers (75-85 years old). At the angle of mouth as well as in the soft palate and pharyngeal wall, a solitary striated muscle fiber (e.g., levator) consistently crossed a fiber bundle of the antagonist muscle (e.g., depressor), but a solitary-to-solitary fiber interdigitation was unlikely with the antagonist muscle. Near the external nasal orifice as well as in the tongue intrinsic muscle layer, at every section, there was a crossing with an endomysium-to-endomysium contact: the nasalis and platysma muscles and; the vertical and transverse (or inferior longitudinal) tongue muscles. Therein, the functional vectors crossed at almost right angle. Also in adult tongue, the vertical and transverse muscle fibers sometimes (0-2 sites per section) crossed with an endomysium-to-endomysium contact. At the muscle crossing with an endomysium contact, the endomysium and basement membrane seemed to receive a friction stress between two muscles. Although some crossings might disappear due to high muscle activity after birth, not a few of them were likely to maintain. To minimize the mechanical stress, a minute nervous control of the timing, duration and strength of muscle contraction seemed to be necessary.

Association of internal exposure of cadmium and lead with periodontal disease: a study of the Fourth Korean National Health and Nutrition Examination Survey.

AIMS: This study was performed to examine the association of the internal exposure of cadmium and lead with periodontitis in a representative sample of adults, who were involved in the Fourth Korea National Health and Nutrition Examination Survey (KNHANES). MATERIALS AND METHODS: One thousand nine hundred and sixty-six subjects over the age of 19 who participated in KNHANES were examined. Cadmium (Cd) and lead (Pb) exposure were grouped into three categories: low (<25th percentile), middle (25th-75th percentile) and high (≥75th percentile). The periodontal status was assessed by the Community Periodontal Index. The multivariate logistic regression analysis was performed to get the adjusted odds ratio (OR), and subgroup analysis was also performed. All analyses considered a complex sampling design. RESULTS: The multivariate logistic regression analysis revealed associations of Cd with periodontitis. Subjects with a high Cd had a 1.57 (95% CI: 1.03-2.38) times higher OR for periodontitis than those with a low Cd. In the subgroup analysis, the association of Pb and Cd with periodontitis was different according to the strata of gender and smoking. CONCLUSIONS: High Cd could be associated with periodontitis in females and current smokers, and middle Pb showed associations in females and non-smokers among a representative sample of adults in Korea.

Effect of unilateral injection of botulinum toxin on lower facial asymmetry as evaluated using three-dimensional laser scanning.

BACKGROUND: Many patients with a hypertrophic masseter muscle desire its reduction to decrease the prominent mandibular angle. Surgical reduction has been widely used to this end, but bilateral injection of botulinum toxin into the masseter muscle is a less-invasive alternative to surgical reduction that has recently become the focus of public interest. The aim of this study was to measure changes in volume and thickness unilaterally in hypertrophic masseter muscles after unilateral botulinum toxin type A (BoNT-A) injection using three-dimensional (3D) laser scanning as a method of evaluation. METHODS AND MATERIALS: The volume and thickness of the lower facial contour of 10 patients with unilateral hypertrophic masseter muscle were measured using 3D laser scanning before and 4, 8, and 12 weeks after a unilateral injection of 25 U of BoNT-A. The 3D scans were superimposed to determine postinjection changes in volume and thickness. RESULTS: Although there was little change in the noninjected side over the experimental period, the mean volume and thickness of the injected side at each time point clearly and statistically significantly decreased between preinjection and 4, 8, and 12 weeks postinjection. CONCLUSION: Unilateral BoNT-A injection appears to be an effective esthetic treatment for patients with muscle-induced facial asymmetry.

BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells.

The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural tissue repair and other regeneration processes are well identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The role of BDNF/TrkB was examined during a 17-day odontogenic differentiation of DPSCs. Human DPSCs were subjected to odontogenic differentiation in dentinogenic media treated with inflammation inducers (LTA or TNFα), BDNF, and a TrkB agonist (LM22A-4) and/or antagonist (CTX-B). Our data show that BDNF and TrkB receptors affect the early and late stages of the odontogenic differentiation of DPSCs. Immunofluorescent data confirmed the expression of BDNF and TrkB in DPSCs. Our ELISA and qPCR data demonstrate that TrkB agonist treatment increased the expression of dentin matrix protein-1 (DMP-1) during early DPSC odontoblastic differentiation. Coherently, the expression levels of runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) were increased. TNFα, which is responsible for a diverse range of inflammation signaling, increased the levels of expression of dentin sialophosphoprotein (DSPP) and DMP1. Furthermore, BDNF significantly potentiated its effect. The application of CTX-B reversed this effect, suggesting TrkB`s critical role in TNFα-mediated dentinogenesis. Our studies provide novel findings on the role of BDNF-TrkB in the inflammation-induced odontoblastic differentiation of DPSCs. This finding will address a novel regulatory pathway and a therapeutic approach in dentin tissue engineering using DPSCs.

Ixeris dentata and Lactobacillus gasseri media protect against periodontitis through Nrf2-HO-1 signalling pathway.

Periodontitis is an infectious inflammation in the gums characterized by loss of periodontal ligaments and alveolar bone. Its persistent inflammation could result in tooth loss and other health issues. Ixeris dentata (IXD) and Lactobacillus gasseri media (LGM) demonstrated strong antioxidant activity, which may prevent oxidative and inflammatory periodontitis. Here, IXD and LGM extracts were investigated for antioxidative activity against oral discomfort and evaluated for their synergistic effect against oxidative and inflammatory periodontitis in a mouse model. IXD/LGM suppressed pro-inflammatory cytokines like interleukin (IL)-1ß, IL-6, and TNF-α. Additionally, it reduced pro-inflammatory mediators, nitric oxide, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) and enhanced AKT, Nrf2, and HO-1 activation. Similarly, IXD/LGM treatment elevated osteogenic proteins and mRNAs; alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2). Hematoxylin and Eosin (H&E) staining and micro-CT analysis confirm the positive impact of IXD/LGM on the periodontal structure and its associated inflammation. These findings demonstrate that IXD/LGM inhibits oxidative stress, periodontal inflammation, and its resultant alveolar bone loss in which Akt (also known as protein kinase B)-nuclear factor-erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling is involved. Thus, IXD/LGM is a potential candidate against oxidative/inflammatory stress-associated periodontitis.