Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis.

OBJECTIVES: The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients. MATERIALS AND METHODS: Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation. RESULTS: Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS. CONCLUSIONS: IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.

Dimensional changes in free gingival grafts at implant sites in the reconstructed mandible: a retrospective study.

OBJECTIVE: To evaluate the dimensional changes in free gingival grafts (FGG) at implant sites in mandibular reconstruction patients. METHODS: Patients who received FGG 4 months after implant placement in the reconstructed mandible with no keratinized mucosa (KM) present were invited for re-examination after 36.7 ± 16.8 months (3.06 ± 1.4 years). Immediately after graft extraction (T0), graft width (GW), graft length (GL), graft thickness (GT), graft dimension (GD), and vertical bone height were documented. Re-examination (T1) included clinical examinations (GW, GL, GD, peri-implant probing depths, and modified Sulcus Bleeding Index), radiographic examination (marginal bone level), and medical chart review. RESULTS: Twenty patients and 62 implants (47 in fibula flaps and 15 in iliac flaps) were included. A significant decrease in GW (51.8%), GL (19.2%), and GD (60.2%), were found between T0 and T1 (p < .001). The univariate analysis showed that GW change was not significantly associated with reconstruction technique, baseline GL, baseline GT, baseline GD, implant location, or type of prosthesis. Implant survival rate of 100% was observed at follow-up. CONCLUSIONS: Within the limitations of the study, free gingival grafts at implant sites in the reconstructed mandible undergo dimensional change that result in a reduction of approximately 60% of the original graft dimension. Graft width decreased over 50%. CLINICAL RELEVANCE: FGG is the standard of care intervention for increasing the amount of KM around implants. This study was the first to evaluate the dimensional change in FGG at implant sites in mandibular reconstruction patients after a medium-term follow-up. CLINICAL TRIAL REGISTRATION: Clinical trial registration is not applicable as this study comprehends a retrospective analysis.

A preliminary investigation into the impact of soft tissue augmentation-based periodontal phenotype modification therapy for patients exhibiting class III decompensation.

BACKGROUND: Patients with skeletal angle Class III malocclusion usually have inadequate hard and soft tissue volume at the mandibular anterior teeth. The labial proclination at the teeth may lead to gingival recession. The purpose of this study was to explore whether periodontal phenotype modification therapy with soft tissue augmentation (PhMT-s) can prevent gingival recession in these patients. METHODS: Four patients with skeletal Class III malocclusion and a thin periodontal phenotype underwent surgical-orthodontic treatment. Prior to tooth movement, they underwent a minimally invasive vestibular incision with subperiosteal tunnel access combined with autogenous connective tissue grafts for periodontal phenotype modification with soft tissue augmentation (PhMT-s). The labial gingival thickness of the anterior mandibular teeth was measured at three distinct levels: at the cementoenamel junction (GT0), 3 mm apical to the CEJ (GT3), and 6 mm apical to the CEJ (GT6). These measurements were taken at baseline, three months following PhMT-s, and after tooth decompensation. Additionally, a biopsy sample was obtained from the PhMT-s site of one patient. All sections were subsequently stained using hematoxylin and eosin, Masson trichrome, Sirius Red, and immunohistochemistry. RESULTS: The thickness of the labial gingiva was increased about 0.42 to 2.00 mm after PhMT-s. At the end of pre-orthognathic surgical orthodontic treatment, the thickness of the labial gingiva was increased about - 0.14 to 1.32 mm compared to the baseline and no gingival recession occurred after the pre-orthognathic surgical orthodontic treatment. The histologic results demonstrated that the grafts obtained from the PhMT-s site exhibited increased deposition of collagen fibers. Moreover, the proportion of type III collagen increased and the grafts displayed significantly reduced positive expression of CD31 and OCN. CONCLUSIONS: PhMT-s increased the thickness of the soft tissue, stabilizing the gingival margin for teeth exhibiting a thin periodontal phenotype and undergoing labial movement. This is attributed to the increased deposition of collagen fibers.

ZEB1 interferes with human periodontal ligament stem cell proliferation and differentiation.

BACKGROUND: Periodontitis can eventually contribute to tooth loss. Zinc finger E-box binding homeobox 1 (ZEB1) is identified as overexpressed in the gingival tissue of mice with periodontitis. This study is designed to decipher the mechanism of ZEB1's involvement in periodontitis. METHODS: Human periodontal mesenchymal stem cells (hPDLSCs) were exposed to LPS to mimic the inflammation in periodontitis. Following ZEB1 silencing, FX1 (an inhibitor of Bcl-6) treatment or ROCK1 overexpression, cell viability, and apoptosis were analyzed. Alkaline phosphatase (ALP) staining, Alizarin red staining, RT-qPCR, and western blot were performed to evaluate osteogenic differentiation and mineralization. hPDLSCs were processed for luciferase reporter assay and ChIP-PCR to confirm the association between ZEB1 and ROCK1. RESULTS: The induction of ZEB1 silencing resulted in reduced cell apoptosis, enhanced osteogenic differentiation, and mineralization. Nevertheless, these effects were significantly blunted by FX1. ZEB1 was confirmed to bind to the promoter sites of ROCK1 and regulate the ROCK1/AMPK. Whereas ROCK1 overexpression reversed the effects of ZEB1 silencing on Bcl-6/STAT1, as well as cell proliferation and osteogenesis differentiation. CONCLUSION: hPDLSCs displayed decreased proliferation and weakened osteogenesis differentiation in response to LPS. These impacts were mediated by ZEB1 regulating Bcl-6/STAT1 via AMPK/ROCK1.

Non-invasive diagnostic potential of salivary miR-25-3p for periodontal disease and osteoporosis among a cohort of elderly patients with type 2 diabetes mellitus.

OBJECTIVE: Osteoporosis (OP) and periodontal disease (PD) are two common health issues that threaten the older population and potentially connected each other in the context of type 2 diabetes mellitus (T2DM). Dysregulated expression of microRNAs (miRNAs) may contribute to the development and progression of both OP and PD among elderly T2DM patients. The present study aimed to evaluate the accuracy of miR-25-3p expression for the detection of OP and PD when compared to a mixed group of patients with T2DM. METHODS: The study recruited 45 T2DM patients with normal bone mineral density (BMD) and healthy periodontium, 40 type 2 diabetic osteoporosis patients coexistent with PD, 50 type 2 diabetic osteoporosis patients with healthy periodontium, and 52 periodontally healthy individuals. miRNA expression measurements in the saliva were determined by real-time PCR. RESULTS: The salivary expression of miR-25-3p was higher in type 2 diabetic osteoporosis patients than patients with T2DM only and healthy individuals (P < 0.05). Among type 2 diabetic osteoporosis patients, those with PD exhibited a higher salivary expression of miR-25-3p than those with healthy periodontium (P < 0.05). Among type 2 diabetic patients with healthy periodontium, a higher salivary expression of miR-25-3p was noted in those with OP than those without (P < 0.05). We also found a higher salivary expression of miR-25-3p in T2DM patients than healthy individuals (P < 0.05). It was revealed that the salivary expression of miR-25-3p was increased as the T scores of BMD of patients were lowered, the PPD and CAL values of patients were enhanced. The salivary expression of miR-25-3p used as a test to predict a diagnosis of PD among type 2 diabetic osteoporosis patients, a diagnosis of OP among type 2 diabetic patients, and a diagnosis of T2DM among healthy individuals produced AUC of 0.859. 0.824, and 0.886, respectively. CONCLUSION: The findings obtained from the study support salivary miR-25-3p confers non-invasive diagnostic potential for PD and OP among a cohort of elderly T2DM patients.

Participants' assessments of the continuing educational program with the delivery mode of a periodontal alliance.

OBJECTIVE: To evaluate the effectiveness of the periodontal continuing educational delivery mode via a periodontal alliance. METHODS: An innovative continuing educational delivery mode via a periodontal alliance has been conducted using a periodontal alliance of 30 hospitals in 18 provinces of China. This delivery mode integrates several instructional methods, including lectures, case presentations, and interactive question and answer sessions, all of which were conducted through online platforms. The effectiveness of the mode was evaluated via a questionnaire that was administered to the participants. The questionnaire consisted of 13 closed-ended questions and 2 open-ended questions. RESULTS: Of the 450 participants, 343 (76%) returned the questionnaire. Of the returned surveys, more than 92% provided positive feedback regarding the instructional methods of the program, stating that the techniques helped them study more efficiently and saved them time and money. More than 85% of the participants were satisfied with the instructional content and more than 90% of the participants considered the educational value of the program to be high, as it helped them identify gaps in knowledge, promoted their ability to establish treatment plans, and encouraged them to network with one another and thereby establish a supportive environment. With respect to the responses to the open-ended questions, the participants claimed that the most useful aspects of the program were related to time and cost savings. The most frequent feedback with respect to improving the program was to include hands-on courses and to divide the program into different levels. CONCLUSIONS: The participants responded positively to the program. The periodontal alliance delivery mode was determined to be an effective way to improve the quality of continuing dental education.

Efficacy Evaluation of Hyaluronic Acid Gel for the Restoration of Gingival Interdental Papilla Defects.

PURPOSE: This clinical study aimed to evaluate the long-term efficacy of reconstruction of the gingival interdental papilla via injection of hyaluronic acid gel. MATERIALS AND METHODS: Eight female participants with Class I or II gingival papilla loss in anterior sites were included in this study. The gingival biotype was evaluated previously. Hyaluronic acid gel was injected into the base of the deficient papilla, which was repeated twice at 3 and 6 weeks after the initial injection. The height of the gingival papilla and the area of papilla loss were examined on clinical photographs before treatment and 3, 6, and 12 months after treatment. The data were tested for a normal distribution and analyzed by the Wilcoxon signed rank test. P < .05 was considered significant. RESULTS: The height of the gingival papilla increased 0.311, 0.45, and 0.4 mm from baseline at 3, 6, and 12 months, respectively, after treatment (P < .05), whereas the area of the black triangle was reduced by 0.31, 0.41, and 0.36 mm2 at the same time points (P < .05). In addition, patients with a thick gingival biotype showed a better effect of treatment on the increase in the height of the gingival papilla and decrease in the area of the black triangle. CONCLUSIONS: Our study verified a remarkable effect of hyaluronic acid gel injection in restoring the deficient gingival papilla of the natural teeth, especially in patients with a thick gingival biotype.

Stem-cell based soft tissue substitutes: Engineering of crosslinked polylysine-hyaluronic acid microspheres ladened with gingival mesenchymal stem cells for collagen tissue regeneration and angiogenesis.

BACKGROUND: The aim of this study was to construct crosslinked polylysine-hyaluronic acid microspheres (pl-HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration. METHODS: The effects of the crosslinked pl-HAM on the biocompatibility and the recruitment of L-929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl-HAMs. RESULTS: The crosslinked pl-HAMs appeared to be completely spherical-shaped particles and had good biocompatibility. L-929 cells and GMSCs grew around the pl-HAMs and increased gradually. Cell migration experiments showed that pl-HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the green fluorescent protein-GMSCs in the pl-HAM group still remain in the soft tissue regeneration area 2 weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis-related indicator CD31 expression in the pl-HAMs+ GMSCs + GeL group compared with the pl-HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co-staining positive cells surrounded the microspheres in both pl-HAMs + GeL group and pl-HAM + GMSCs + GeL group. CONCLUSIONS: The crosslinked pl-HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future.

Different doses of vitamin D supplementation to nonsurgical treatment for vitamin-D-insufficient patients with diabetic periodontitis and the effect on gingival BMP-2 levels.

Epidemiological data show people with diabetes mellitus (DM) have three-fold increase in risk of periodontitis. A vitamin D insufficiency can affect the progression of DM and periodontitis. This study evaluated the effects of different-dose vitamin D supplementation to nonsurgical periodontal therapy for vitamin-D-insufficient diabetic patients coexisting with periodontitis and changes of gingival bone morphogenetic protein-2 (BMP-2) levels. The study included 30 vitamin-D-insufficient patients receiving nonsurgical treatment followed by administration of 25,000 international units (IU) vitamin D3 per week (the low-VD group) and 30 patients receiving 50,000 UI vitamin D per week (the high-VD group). The decreases of probing pocket depth, clinical attachment loss, bleeding index, and periodontal plaque index values of patients after the six-month supplementation of 50,000 UI vitamin D3 per week to nonsurgical treatment were more significant than those after the six-month supplementation of 25,000 UI vitamin D3 per week to nonsurgical treatment. It was found that 50,000 IU per week vitamin D supplementation for 6 months could lead to a better glycemic control for vitamin-D-insufficient diabetic patients coexisting with periodontitis after nonsurgical periodontal therapy. Increased levels of serum 25(OH) vitamin D3 and gingival BMP-2 were found in both low- and high-dose VD groups, and the high-dose VD group exhibited higher levels than the low-dose VD group. Vitamin D supplementation in large doses for 6 months tended to improve the treatment of periodontitis and increase gingival BMP-2 levels in diabetic patients coexisting with periodontitis who were vitamin D deficient.

Study of the Friction Behavior of Embedded Fibers in YG8 Surface Grooves.

YG8 is a common cemented carbide material with excellent mechanical properties and mechanical properties, so it is widely used in the actual industry. However, due to the active chemical properties and strong affinity of tungsten alloy steel, it is easy to produce bonding and peeling in application, resulting in an unstable process and short service life. In order to control and reduce the surface wear of YG8 cemented carbide, groove-textured surface (GS) and flocking surface (FS) were prepared on smooth surface (SS). The friction characteristics of the samples were studied under different applied load conditions. The results show that the average friction coefficient of SS, GS and FS is inversely proportional to the load in dry/oil environment. Compared with SS, FS exhibits the lowest friction coefficient, which is reduced by 30.78% (dry friction) and 13.13% (oil lubrication). FS effectively improves the tooth jump phenomenon of the sample and the amplitude of the friction coefficient, friction force and load, and has the best anti-friction characteristics. At the same time, the FS with the fastest contact angle drop at any time also showed excellent wetting ability, and the wear rate decreased by an order of magnitude. The implantation of fibers in the groove inhibits the spalling and furrow of wear track, which is attributed to the effect of fibers on damage repair. In the friction process, FS increases the content of the O element and induces the formation of oxides. The friction mechanism is mainly chemical wear. The excellent tribological properties of FS have a good guiding significance and theoretical support for improving the tribological properties of high hardness material surfaces.

Histiocytoid giant cellulitis-like Sweet syndrome at the site of sternal aspiration: A case report and review of literature.

BACKGROUND: Giant cellulitis-like Sweet syndrome (SS) is a rare subtype of SS, and reports of the combined histiocytoid type of pathology are scarce. Here, we report a case of SS with distinctive clinical presentations and which was difficult to distinguish from cellulitis. By sharing this case and a discussion of the related literature in detail, we aim to provide clinicians with new insights into the characteristics of histiocytoid giant cellulitis-like (HGC)-SS and the pathogenesis of SS. CASE SUMMARY: A 52-year-old male was admitted after experiencing progressive fatigue for 1 mo and tongue swelling with pain for 1 d. He was diagnosed with myelodysplastic syndrome (MDS) and angioneurotic edema of the tongue and floor of the mouth. However, 7 d after examination by sternal aspiration, a violaceous, tender, and swollen nodule developed at the site, with poorly demarcated erythema of the surrounding skin. Considering his profile of risk factors, the diagnosis of cellulitis was made and he was administered broad-spectrum antibiotics. When the lesion continued to worsen and he developed chills and fever, pathogenic and dermatopathological examination led to the diagnosis of HGC-SS. Treatment with prednisone led to the fever being relieved within 24 h and the skin lesion being resolved within 1 wk. The patient refused intensive treatment and was instead given thalidomide, erythropoietin, stanozolol, and supportive care. The prednisone was gradually tapered, with no signs of recurrence, but he died 2 mo later of severe pneumonia. CONCLUSION: HGC-SS demonstrates unique manifestation. SS and leukemia cutis share cytological origin. Myelofibrosis and SS are adverse prognostic factors for MDS.

No Genetic Causal Association Between Periodontitis and Arthritis: A Bidirectional Two-Sample Mendelian Randomization Analysis.

Objectives: Periodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the association between PD and arthritis is causal. The purpose of this study was to investigate the causal association of PD with arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA). Methods: We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy. Results: Genetically determined PD did not have a causal effect on OA (OR = 1.06, 95% CI: 0.99-1.15, P = 0.09) and RA (OR = 0.99, 95% CI: 0.87-1.13, P = 0.89). Furthermore, we did not find a significant causal effect of arthritis on PD in the reverse MR analysis. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis. Conclusions: Our MR analysis reveals non-causal association of PD with arthritis, despite observational studies reporting an association between PD and arthritis.

Poloxamer 407 Induces Hypertriglyceridemia but Decreases Atherosclerosis in Ldlr-/- Mice.

BACKGROUND: Hypertriglyceridemia (HTG) increases the risk for atherosclerotic cardiovascular disease, but underlying mechanisms are incompletely understood. Circulating monocytes play an important role in atherogenesis by infiltrating arterial walls, where they differentiate into macrophages. We tested the hypothesis that HTG is mechanistically linked to atherogenesis by altering the monocyte phenotype and infiltration into atherosclerotic lesions in a model of diet-induced atherogenesis in Ldlr-/- mice. METHODS: HTG was induced in male Ldlr-/- mice, fed a Western, high-fat high-cholesterol diet, by daily injection of poloxamer 407 (P407), a lipoprotein lipase inhibitor, for seven weeks. Atherosclerosis, monocyte phenotypes, and monocyte migration into atherosclerotic lesions were determined by well-validated methods. RESULTS: Compared with the saline control, P407 injection in Ldlr-/- mice rapidly induced profound and persistent HTG, modestly elevated plasma cholesterol levels, and increased levels of triglyceride and cholesterol carried in very-low-density lipoprotein and low-density lipoprotein. Unexpectedly, mice receiving P407 versus saline control showed less atherosclerosis. Following induction of HTG by P407, CD36+ (also CD11c+), but not CD36- (CD11c-), monocytes showed early increases in lipid accumulation, but the number of CD36+ (not CD36-) monocytes was dramatically decreased afterwards in the circulation until the end of the test. Concurrently, CD36+ (CD11c+) monocyte migration into atherosclerotic lesions was also reduced in mice receiving P407 versus controls. CONCLUSIONS: P407 induced severe HTG, but reduced atherosclerosis, in Ldlr-/- mice, possibly because of profound reductions of circulating CD36+ (CD11c+) monocytes, leading to decreased monocyte migration into atherosclerotic lesions.

Coordination Polymer-Coated CaCO3 Reinforces Radiotherapy by Reprogramming the Immunosuppressive Metabolic Microenvironment.

Radiotherapy is widely exploited for the treatment of a large range of cancers in clinic, but its therapeutic effectiveness is seriously crippled by the tumor immunosuppression, mainly driven by the altered metabolism of cancer cells. Here, a pH-responsive nanomedicine is prepared by coating calcium carbonate (CaCO3 ) nanoparticles with 4-phenylimidazole (4PI), an inhibitor against indoleamine 2,3-dioxygenase 1 (IDO-1), together with zinc ions via the coordination reaction, aiming at reinforcing the treatment outcome of radiotherapy. The obtained pH-responsive nanomedicine, coined as acidity-IDO1-modulation nanoparticles (AIM NPs), is able to instantly neutralize protons, and release 4PI to suppress the IDO1-mediated production of kynurenine (Kyn) upon tumor accumulation. As a result, treatment with AIM NPs can remarkably enhance the therapeutic efficacy of radiotherapy against both murine CT26 and 4T1 tumors by eliciting potent antitumor immunity. Furthermore, it is shown that such combination treatment can effectively suppress the growth of untreated distant tumors via the abscopal effect, and result in immune memory responses to reject rechallenged tumors. This work highlights a novel strategy of simultaneous tumor acidity neutralization and IDO1 inhibition to potentiate radiotherapy, with great promises to suppress tumor metastasis and recurrence by eliciting robust antitumor immunity.

[Advances in parallel artificial membrane permeability assay and its applications].

With the development of drug discovery, more and more candidate compounds need to be studied. Methods that can screen compound rapidly received significant attention. Parallel artificial membrane permeability assay (PAMPA) as a powerful tool has been applied to drug studies. It uses an artificial lipid membrane to mimic the barrier for drug permeability studies. This article introduces the establishment and characteristics of PAMPA, as well as its applications in screening compounds. It can be used as models (e.g. predicting the ability of compound in gastro-intestinal absorption, blood-brain barrier transportation and skin penetration) by changing the component of artificial lipid membrane. PAMPA has advantages in high throughput selection of valuable compound with low cost, versatile, low dose, and good reproducibility.

Hyaluronic acid vs. physiological saline for enlarging deficient gingival papillae: a randomized controlled clinical trial and an in vitro study.

BACKGROUND: loss of the interdental papillae leads to the formation of a black triangle, which compromises smile esthetics and contributes to food impaction and plaque accumulation. The aim of this study was to evaluate the efficacy of the injection of hyaluronic acid (HA) and compare it to that of physiological saline solution in the restoration of deficient gingival papillae in vivo and in vitro. METHODS: Twenty-four patients with 68 deficient gingival papillae were recruited for this clinical trial with a split-mouth design. The deficient gingival papillae on one side of the anterior maxilla were injected with HA, and those on the other side were injected with physiological saline solution. The heights of the gingival papillae and the areas of the black triangles were measured from clinical photographs obtained before and 6 and 12 months after treatment. Additionally, the proliferation and migration of gingival fibroblasts were evaluated after HA and physiological saline treatment by an in vitro study. RESULTS: the results revealed that the injection of HA yielded 0.198 and 0.28 mm gingival papilla increasement at 6 and 12 months, respectively, relative to the baseline (P<0.05). However, deficient gingival papillae also grew by 0.278 mm at 12 months in the group that received physiological saline solution (P<0.05). The injection of HA significantly improved deficient gingival papillae 6 months earlier than the injection of physiological saline solution. HA also significantly accelerated the proliferation and migration of gingival fibroblasts in vitro. CONCLUSIONS: The present study confirms that the injection of HA could increase the height of gingival papillae for improving gingival papilla defects. However, the effect is not superior to that of physiological saline solution. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-ONC-17011781) (28/06/2017). http://www.chictr.org.cn/showproj.aspx?proj=19931.

Fluoride resistance in fibroblasts is conferred via reduced susceptibility to oxidative stress and apoptosis.

Chronic fluoride exposure from drinking water may result in endemic fluorosis. To better understand the mechanisms by which some people are resistant to fluorosis, here we investigated the effect of treatment with NaF (sodium fluoride) on production of reactive oxygen species (ROS), morphological changes in mitochondria, the mRNA expression of Fas ligand (Fas-L), and the protein expression of cleaved caspase-3 in regular L-929 cells and fluoride-resistant (FR) L-929 cells. While morphological changes indicative of apoptosis and a network of fragmented mitochondria were observed in regular L-929 cells after NaF treatment, there were no morphological changes in FR L-929 cells after NaF treatment. Treatment with 10 mm NaF induced a significant difference in the production of ROS, triggered the expression of cleaved caspase-3, and upregulated the mRNA expression of Fas-L in regular L-929 cells. However, there was no significant production of ROS in FR L-929 cells. Additionally, cleaved caspase-3 and upregulated Fas-L were not detected in FR L-929 cells. These results suggest that FR fibroblasts are resistant to oxidative stress and apoptosis induced by fluoride.

Attenuated Salmonella typhimurium-mediated tumour targeting imaging based on peptides.

Attenuated bacteria-mediated tumor targeting diagnosis will provide a novel strategy for further cancer treatments owing to the intrinsic facultative anaerobic characteristic of bacteria and rapid proliferation in the tumor sites. In this work, we firstly investigate the in vivo behaviour of the attenuated Salmonella typhimurium (S. typhimuriumΔppGpp/lux) after intravenous injection. S. typhimurium exhibits rapid proliferation in tumor sites after three days of injection through bioluminescence imaging, the Luria-Bertani plate and the Gram-staining assay. In contrast, S. typhimurium does not proliferate in the normal tissues and could be excreted from the body of mice. Afterwards, a targeting peptide ubiquicidin (UBI) labeled with fluorescent dye Cy5.5 or radionuclide 125I was intravenously injected into the mice with or without S. typhimurium treatments for in vivo fluorescence imaging and single-photon emission computed tomography (SPECT/CT) imaging, respectively. The results show that the peptide UBI could specifically target the two independent bacteria-infected tumor models, the 4T1 murine breast cancer model and the CT26 mouse colon cancer model, realizing the sensitive multimodal imaging of tumors. Such a strategy (bacteria-mediated tumor targeting) may further improve the sensitivity to early diagnosis of tumors. We hope that our developed strategy could further be extended to cancer theranostics in the future, bringing good news for cancer patients.

Sodium fluoride causes oxidative stress and apoptosis in cementoblasts.

OBJECTIVES: Toothpaste with fluoride concentration up to 5000 ppm are recommended to the patients who are susceptible to root caries; however, the effects of fluoride on cementoblasts have received less attention. METHODS: The OCCM-30 cells were exposed to 0,0.5, 5, 10 mM NaF respectively. A TUNEL (TdT-mediated dUTP-biotin nick end labeling) assay kit was used to detect the DNA fragmentation. Hoechst staining was used to determine changes of nuclear morphology. Real-time quantitative RT-PCR and Western blotting were performed to investigate the mRNA and protein expression of caspase-3,-8,-9, cleaved Poly (ADP-ribose) polymerase (PARP) and Fas-ligand (Fas-L), a ligand of death receptor. CA-DCF-DA [5 (6)-Carboxy-2',7'-dichlorofluorescein diacetate] was used to measure the generation of reactive oxygen species (ROS) in OCCM-30 cells after the NaF stimulation. RESULTS: The results showed apoptotic morphological changes and DNA fragmentation in OCCM-30 cells exposed to high concentration of NaF. 10 mM NaF induced the expression of cleaved caspase-3,-8,-9 and cleaved Poly (ADP-ribose) polymerase (PARP). The mRNA expression of the Fas-L was also increased in cells exposed to 5 mM NaF. Furthermore, 10 mM NaF stimulation resulted in a significant generation of ROS in the OCCM-30 cells. CONCLUSIONS: Our research demonstrated that apoptosis is activated by NaF in OCCM-30 cells through both of the extrinsic death receptor-dependent and oxidative stress-related intrinsic apoptotic pathway. CLINICAL SIGNIFICANCE: More consideration should be given about the fluoride concentration and the frequency of dental products when used to prevent the root caries for patients with gingival recession.

[Survey of periodontal health in medical college students after 3 years of periodontal health maintenance].

PURPOSE: To observe and evaluate the status of periodontal disease in young people and the effect of intervention to control the development of periodontal diseases. METHODS: One hundred and fifty-three medical college students were randomly divided into group A (receiving interventions) and group B (no interventions). They were followed up for 3 years. The subjects in group A received oral health education, including selection of the toothbrush, the right way to brush teeth, the use of dental floss and interdental brush. At the same time ,they were given initial periodontal treatment according to the actual situation, and received oral health education, periodontal maintenance treatment, and reinforced plaque control every six months. The changes of debris index (DI), calculus index (CI), probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP) and gingival index (GI) before and after interventions were compared. Statistical analysis was performed using SAS 6.12 software package. RESULTS: Three years later, CI and DI in group A declined significantly compared to the baseline (P<0.01), but there was no significant changes in group B (P>0.05). There was significant difference in the changes of PD, BOP and GI between group A and B (P<0.01). Significant difference of the change of CAL between group A and B was also found(P<0.05), CAL in group B was significantly higher than that in group A. CONCLUSIONS: There are positive effects of regular periodontal health maintenance and oral health education on periodontal health.