Gastrodin Liposomes Block Crosstalk between Astrocytes and Glioma Cells via Downregulating Cx43 to Improve Antiglioblastoma Efficacy of Temozolomide.

The crosstalk between glioma cells and astrocytes plays a crucial role in developing temozolomide (TMZ) resistance of glioblastomas, together with the existence of the BBB contributing to the unsatisfactory clinical treatment of glioblastomas. Herein, we developed a borneol-modified and gastrodin-loaded liposome (Bo-Gas-LP), with the intent of enhancing the efficacy of TMZ therapy after intranasal administration. The results showed that Bo-Gas-LP improved GL261 cells' sensitivity to TMZ and prolonged survival of GL261-bearing mice by blocking the crosstalk between astrocytes and glioblastoma cells with the decrease of Cx43. Our study showed that intranasal Bo-Gas-LP targeting the crosstalk in glioblastoma microenvironments proposed a promising targeted therapy idea to overcome the current therapeutic limitations of TMZ-resistant glioblastomas.

Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial.

BACKGROUND AND AIMS: Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). RESULTS: Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P = .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P = .2370) between the 2 groups. CONCLUSIONS: The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar. (Clinical trial registration number: NCT05465889.).

Expression of deubiquitinases in human gingiva and cultured human gingival fibroblasts.

BACKGROUND: Although deubiquitinating enzymes (DUBs) such as CYLD, A20 and OTULIN are expressed in multiple tissues and thought to be linked with inflammatory diseases, their expression in periodontal tissues remains to be determined. This research was designed to assess the expression of CYLD, A20 and OTULIN in human gingiva, and to evaluate the regulation of these DUBs in human gingival fibroblasts (HGFs) upon different stimuli. METHODS: Immunohistochemistry assay was conducted to determine the expression of CYLD, A20 and OTULIN in human gingiva. Immunofluorescence assay was employed to observe the protein expression of CYLD, A20 and OTULIN in HGFs. RT-PCR and western blots were carried out to assess gene and protein expression changes of these DUBs in HGFs upon LPS or TNF-α. RESULTS: CYLD, A20 and OTULIN were found to be expressed in human gingiva and HGFs. The expression of CYLD, A20 and OTULIN was lower in the inflamed gingival tissue samples compared with the healthy gingival tissue samples. Further, the expression of CYLD, A20 and OTULIN in HGFs exhibited distinct regulation by different stimuli. TNF-α treatment markedly increased NF-κB activation in HGFs CONCLUSIONS: Our findings suggest that CYLD, A20 and OTULIN might play a role in the progression of periodontitis.

Mechanism of NF-κB signaling pathway and autophagy in the regulation of osteoblast differentiation.

OBJECTIVE: The objective of the present work was to investigate a possible mechanism of NF-κB signaling pathway and autophagy in the regulation of osteoblast differentiation, and provide experimental basis for the study of tooth eruption disorder. METHODS: Mouse osteoblast-like (MC3T3-E1) cells were inoculated with a cell density of 70%. According to the grouping experimental design, Western blot and monodansylcadaverine (MDC) detection were conducted after dosing for 24 h. The cells were divided into the following five groups: blank control group; 6.25 µg/mL SN50 group; 12.5 µg/mL SN50 group; 25 µg/mL SN50 group and 50 µg/mL SN50 group. RESULTS: Western blot analysis revealed that the expression of LC3 protein was present in the blank control group; 6.25 µg/mL SN50 group; 12.5 µg/mL SN50 group and 50 µg/mL SN50 group, with no significant differences among these groups. However, the expression of LC3 protein was significantly lower in the 25 µg/mL SN50 group. MDC detection showed that, in the blank control group; 6.25 µg/mL SN50 group; 12.5 µg/mL SN50 group and 50 µg/mL SN50 group, there was obvious green fluorescence in the cytoplasm of the osteoblasts. However, in the 25 µg/mL SN50 group, it was found that there were significantly fewer green fluorescent particles. CONCLUSION: The osteoblast itself had a strong function of autophagy. The appropriate concentration of SN50 in blocking the NF-κB pathway of the osteoblast was associated with the obvious inhibition of autophagy. However, the relationship between NF-κB signaling pathway and autophagy in the process of tooth eruption requires further study.

Effects of periodontal therapy on serum lipid profile and proinflammatory cytokines in patients with hyperlipidemia: a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate whether periodontal treatment in patients with periodontitis and hyperlipidemia may have any influence on plasma lipids and pro-inflammatory cytokine levels. MATERIAL AND METHODS: We randomly assigned 109 patients with hyperlipidemia and chronic periodontitis into group 1 (n = 55) and group 2 (n = 54). Patients in group 1 underwent a standard cycle of supragingival mechanical scaling and polishing. Patients in group 2 underwent the adjunctive full-mouth intensive removal of subgingival dental plaque biofilms with the use of scaling and root planning. Periodontal parameters, total cholesterol (TC), triglyceride (TRG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-alpha (TNF-α), interleukin(IL)-1ß(IL-1ß), and IL-6 were evaluated before treatment and 2 and 6 months after treatment. RESULTS: Two and 6 months after treatment, TRG levels were significantly lower in group 2 than in group 1 (P < 0.05), and the levels of HDL-C were significantly higher (P < 0.05). Two and 6 months after therapy, the levels of TNF-α were significantly lower in group 2 than in group 1 (P < 0.05), as were the levels of IL-1ß (P < 0.001) and IL-6 (P < 0.001). CONCLUSIONS: Intensive periodontal treatment of participants with hyperlipidemia and chronic periodontitis improved serum lipid levels and decreased circulating pro-inflammatory cytokine levels. CLINICAL RELEVANCE: This study showed that intensive treatment of periodontitis results in an improvement in serum lipid levels and a decrease in serum proinflammatory cytokine levels in patients with periodontitis and hyperlipidemia. These findings may contribute to present knowledge that periodontal therapy may be beneficial for individuals with hyperlipidemia.

[Valacyclovir as an adjunct to full-mouth scaling and root planing of advanced chronic periodontitis:a randomized clinical trail].

PURPOSE: The aim of this study was to evaluate the clinical benefit of valacyclovir when performing full-mouth periodontal debridement in patients with advanced chronic periodontitis. METHODS: Fifty-nine patients with advanced chronic periodontitis were randomly assigned into control-treatment group(n=29) and intensive-treatment group(n=30). All patients were given instructions of basic oral hygiene and a standard cycle of supragingival mechanical scaling and polishing. Patients in the intensive-treatment group received oral valacyclovir for 1 week, while patients in the control-treatment group received placebo. Thereafter, patients in both groups underwent full-mouth intensive removal of subgingival dental plaque biofilms with the use of scaling and root planing within 48 hours. Periodontal parameters were evaluated before treatment and 2 or 6 months after treatment. The data was statistically analyzed using SPSS17.0 software package. RESULTS: No significant difference in clinical parameters was noted before treatment. 2 and 6 months after treatment, the mean percentage reduction of sites with BOP and PD≥4 mm were significantly higher in the intensive-treatment group than in the control-treatment group (P<0.05). Similarly, patients in the intensive-treatment group had higher mean PD reduction than those in the control-treatment group 2 months (P<0.05) and 6 months after therapy (P<0.05). However, the mean values of CAL reduction were slightly and not significantly higher in the intensive-treatment group than in the control-treatment group after therapy. CONCLUSIONS: It may be concluded that valacyclovir significantly improves clinical results of full-mouth non-surgical periodontal debridement in advanced chronic periodontitis.

Clinical and genetic evaluation of a Chinese family with isolated oligodontia.

OBJECTIVES: Oligodontia is defined as the congenital absence of 6 or more permanent teeth excluding the third molar. Tooth agenesis may be classified as syndromic/non-syndromic and as familial/sporadic. To date, more than 300 genes have been found to be involved in tooth development, but only a few of these genes, such as MSX1, PAX9 and AXIN2, are related to the condition of non-syndromic oligodontia. The objective of the present work was to investigate the disease-causing gene of non-syndromic oligodontia in a Han Chinese family and analyse the pathogenesis of mutations that result in oligodontia. DESIGN: We examined all individuals of the oligodontia family by clinical and radiographic examinations. Based on the clinical manifestations, the candidate genes MSX, PAX9 and AXIN2 were selected to analyse and screen for mutations. RESULTS: The clinical evaluation suggested that the family might show non-syndromic oligodontia. DNA sequencing of the MSX1 gene revealed two mutations in the two patients with oligodontia: a heterozygotic silent mutation, c.348C>T (P.Gly116=), in exon 1 and a homozygotic deletion of 11 nucleotides (c.469+56delins GCCGGGTGGGG) in the intron. However, the silent mutation and the deletion mutation were thought to be known polymorphisms (rs34165410 and rs34341187) by bioinformatics analysis. We did not detect any mutations in the PAX9 and AXIN2 genes of oligodontia patients. CONCLUSION: Our finding suggests that identified polymorphisms (c.348C>T and c.469+56delins GCCGGGTGGGG) may be responsible for the oligodontia phenotype in this Chinese family, but the association requires further study.

Could MTA be a novel medicine on the recurrence therapy for GCTB?

Giant cell tumor of bone (GCTB) is a benign locally aggressive bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. Surgical treatment of GCTB is associated with high morbidity, and local recurrence. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease. If the tumor reaches close to the articulating surface a subchondral bone graft can be performed without risking a higher recurrence rate. Mineral trioxide aggregate (MTA) has been widely used to repair various kinds of tooth perforations. MTA is a powder aggregate containing mineral oxides with a good biological action and may facilitate the regeneration of the periodontal ligament and formation of bone. MTA used was able to induce bone regeneration and had its action optimized. Study has showed that, in the presence of MTA, cells grow faster and produce more mineralized matrix gene expression in osteoblasts. We hypothesize that MTA may has anti-recurrence properties. For the clinical point of view, we can apply MTA in the GCTB to induce bone production, then to inhibit the recurrent of the cases. MTA may be the therapy of choice for primary as well as recurrent giant cell tumors of bone.

[Family tree and restoration method of hereditary opalescent dentin: a case report].

Hereditary opalescent dentin is a rare autosomal dominant inherited disease of dentin development. A case of hereditary opalescent dentin was reported, and the pathogenesis, family tree and restoration methods were reviewed.