Search Results (7)

The sodium–citrate cotransporter (NaCT) plays a crucial role in citrate transport during amelogenesis. Mutations in the SLC13A5 gene, which encodes the NaCT, cause early infantile epileptic encephalopathy 25 and amelogenesis imperfecta. We analyzed developing pig molars and determined that the citrate concentrations in secretory- and maturation-stage enamel are both 5.3 µmol/g, with about 95% of the citrate being bound to mineral. To better understand how citrate might enter developing enamel, we developed Slc13a5^Flag reporter mice that express NaCT with a C-terminal Flag-tag (DYKDDDDK) that can be specifically and accurately recognized by commercially available anti-Flag antibodies. The 24-base Flag coding sequence was located immediately upstream of the natural translation termination codon (TAG) and was validated by Sanger sequencing. The general development, physical activities, and reproductive outcomes of this mouse strain were comparable to those of the C57BL/6 mice. No differences were detected between the Slc13a5^Flag and wild-type mice. Tooth development was extensively characterized using dissection microscopy, bSEM, light microscopy, in situ hybridization, and immunohistochemistry. Tooth formation was not altered in any detectable way by the introduction of the Flag. The Slc13a5^Flag citrate transporter was observed on all outer membranes of secretory ameloblasts (distal, lateral, and proximal), with the strongest signal on the Tomes process, and was detectable in all but the distal membrane of maturation-stage ameloblasts. The papillary layer also showed positive immunostaining for Flag. The outer membrane of odontoblasts stained stronger than ameloblasts, except for the odontoblastic processes, which did not immunostain. As NaCT is thought to only facilitate citrate entry into the cell, we performed in situ hybridization that showed Ank is not expressed by secretory- or maturation-stage ameloblasts, ruling out that ANK can transport citrate into enamel. In conclusion, we developed Slc13a5^Flag reporter mice that provide specific and sensitive localization of a fully functional NaCT-Flag protein. The localization of the Slc13a5^Flag citrate transporter throughout the ameloblast membrane suggests that either citrate enters enamel by a paracellular route or NaCT can transport citrate bidirectionally (into or out of ameloblasts) depending upon local conditions. Full article

Objectives: Dental erosion has evolved into a common condition with growing concern in the dental community. The aim of this study was to explore the protective effects of two highly fluoridated products, silver fluoride solution (silver diamine fluoride-potassium iodide solution, SDF-KI) and fluoride varnish, on dental erosion in mouse. Methods: Two groups of ten young CD-1 mouse were given a cola drink ad libitum over a 6-week period. A prophylactic treatment with a silver fluoride solution (38% SDF 48,000 ppm F with a silver concentration of 253,900 ppm) and a fluoride varnish (NaF, 22,600 ppm F) were applied on the mandibular molars, performed under sedation twice a week during the whole experiment. Furthermore, two control groups of ten mice were included, a positive (cola drink) and a negative (distilled water) control. A terminal procedure was followed by dissection of mandibular molars and analysis of them using scanning electron microscopy (SEM). The first molars were transversely ground, further analyzed by SEM, and measured for tooth height and tooth tissue loss. Results: Analyses of mandibular molars treated with a fluoride varnish indicated a 5% decreased tooth tissue loss, compared to the molars which served as a positive control. The best effect was achieved with the application of silver fluoride solution, displaying a 35% decreased tooth tissue loss compared to the positive control group. Conclusions: Preventive treatment with a solution of silver fluoride solution exhibits greater protection against dental erosion compared to a traditional fluoride varnish. This study indicates that silver fluoride solution is an effective fluoride compound and is highly beneficial in a clinical setting with the aim of preventing dental erosion. Full article

The inflammatory cytokine response is essential for protective immunity, yet bacterial and viral pathogens often elicit an exaggerated response (“cytokine storm”) harmful to the host that can cause multi-organ damage and lethality. Much has been published recently on the cytokine storm within the context of the coronavirus pandemic, yet bacterial sepsis, severe wound infections and toxic shock provide other prominent examples. The problem of the cytokine storm is compounded by the increasing incidence of multidrug-resistant bacterial strains. We created an incisive molecular tool for analyzing the role of the B7/CD28 costimulatory axis in the human inflammatory response. To attenuate the cytokine storm underlying infection pathology, yet preserve host defenses, we uniquely targeted the engagement of CD28 with its B7 co-ligands by means of short peptide mimetics of the human CD28 and B7 receptor homodimer interfaces. These peptides are not only effective tools for dissecting mechanism but also serve to attenuate the inflammatory response as a broad host-oriented therapeutic strategy against the cytokine storm. Indeed, such peptides protect mice from lethal Gram-positive bacterial superantigen-induced toxic shock even when dosed in molar amounts well below that of the superantigen and show promise in protecting humans from the severe inflammatory disease necrotizing soft tissue infections (‘flesh-eating’ bacterial sepsis) following traumatic wound injuries. Full article

Background: To establish an immediate implantation rat model and to evaluate the effects of pre-existing periodontitis and two different socket rinse solutions on immediate implantation prognosis. Methods: Sprague-Dawley (SD) rats were randomly divided into three groups before immediate implantation, including the control group, the group with experimentally induced periodontitis (EP), in which rats have been experimentally induced periodontitis before implantation, and the group with induced periodontitis and with extraction sockets rinsed with three percent H₂O₂ (EP-H₂O₂), in which rats have been induced periodontitis before implantation, and extraction sockets were rinsed with three percent H₂O₂. Periodontitis was induced by ligating the thread around the molars for four weeks. Six weeks after titanium alloy implants were self-tapped and left to heal transmucosally, maxillae were dissected after the clinical examination to perform micro-CT and histological analysis. Results: An immediate implantation model was successfully built in rats. There was no significant difference in implant survival rates between the EP and control groups. However, the clinical examination results, micro-CT analysis, and histological analysis in EP and EP-H₂O₂ groups showed a significantly worse prognosis than in the control group. Three percent H₂O₂ showed a similar effect with saline. Conclusion: This study presented a protocol for establishing a rat immediate implantation model and showed that periodontitis history might negatively affect the prognosis of immediate implantation. These findings urge caution and alternative strategies for patients with periodontal disease history, enhancing the long-term success of immediate implantation in dental practice. Additionally, the comparable outcomes between 3% H₂O₂ and saline suggest the use of saline as a cost-effective and safer alternative for implant site preparation in dental practice. Full article

The aim of this research was to evaluate the mechanical impact of utilizing different fiber-reinforced composite (FRC) systems to reinforce inlay-retained bridges in dissected lower molars with different levels of periodontal support. A total of 24 lower first molars and 24 lower second premolars were included in this study. The distal canal of all molars received endodontic treatment. After root canal treatment, the teeth were dissected, and only the distal halves were kept. Standardized class II occluso-distal (OD) (premolars) and mesio-occlusal (MO) (dissected molars) cavities were prepared in all teeth, and premolar–molar units were created. The units were randomly distributed among four groups (n = six/group). With the aid of a transparent silicone index, direct inlay-retained composite bridges were fabricated. In Groups 1 and 2, both discontinuous (everX Flow) and continuous (everStick C&B) fibers were used for reinforcement, while in Groups 3 and 4, only discontinuous fibers (everX Flow) were used. The restored units were embedded in methacrylate resin, simulating either physiological periodontal conditions or furcation involvement. Subsequently, all units underwent fatigue survival testing in a cyclic loading machine until fracture, or a total of 40,000 cycles. Kaplan–Meyer survival analyses were conducted, followed by pairwise log-rank post hoc comparisons. Fracture patterns were evaluated visually and with scanning electron microscopy. In terms of survival, Group 2 performed significantly better than Groups 3 and 4 (p < 0.05), while there was no significant difference between the other groups. In the case of impaired periodontal support, a combination of both continuous and discontinuous short FRC systems increased the fatigue resistance of direct inlay-retained composite bridges compared to bridges that only contained short fibers. Such a difference was not found in the case of sound periodontal support between the two different bridges. Full article

In recent year, cationic liposomes have gained a lot of attention for siRNA delivery. Despite this, intracellular barriers as endosomal escape and cytosolic delivery of siRNA still represent a challeng, as well as the cytotoxicity due to cationic lipids. To address these issues, we developed four liposomal formulations, composed of two different cationic lipids (DOTAP and DC-Cholesterol) and different ratio of co-lipids (cholesterol and DOPE). The objective is to dissect these impacts on siRNA efficacy and cytotoxicity. Liposomes were complexed to siRNA at six different N/P molar ratios, physico-chemical properties were characterized, and consequently, N/P 2.5, 5 and 10 were selected for in vitro experiments. We have shown that cytotoxicity is influenced by the N/P ratio, the concentration of cationic lipid, as well as the nature of the cationic lipid. For instance, cell viability decreased by 70% with liposomes composed of DOTAP/Cholesterol/DOPE 1/0.75/0.5 at a N/P ratio 10, whereas the same formulation at a N/P ratio of 2.5 was safe. Interestingly, we have observed differences in terms of mRNA knock-down efficiency, whereas the transfection rate was quite similar for each formulation. Liposomes containing 50% of DOPE induced a mRNA silencing of around 80%. This study allowed us to highlight crucial parameters in order to develop lipoplexes which are safe, and which induce an efficient intracytoplasmic release of siRNA. Full article

Ectopic molars within the mandibular ramus/condyle unit, although rare, present a unique challenge to the surgeon. Multiple approaches have been described in the literature for their removal. A review of the English literature on the subject of mandibular ectopic molars and their epidemiology, etiology, indications for removal, and surgical techniques was completed. In addition, a case report is presented of an ectopic mandibular molar in the mid-ramus region which was removed via a minimally invasive, intraoral, technique combining the use of endoscopy and piezoelectric surgery. The authors advocate this technique as it offers the following advantages: avoidance of injury to branches of the facial nerve, unaesthetic scars, and sialocele formation; maximization of surgical field visualization with limited dissection; ability for safe sectioning of the tooth with minimal risks to adjacent structures; and precise bone removal, reducing the risk of iatrogenic or postoperative mandible fracture. Full article