Exploring the causal relationship between gastroesophageal reflux and oral lesions: A mendelian randomization study.

Background: Clinical observations and retrospective studies have observed that patients with gastroesophageal reflux disease (GERD) have an increased probability of dental erosion, periodontitis and oral mucosal lesions and other common oral lesions. However, whether there is a genetic causal relationship between GERD and the occurrence of oral lesions has not been reported. Methods: In this study, we extracted instrumental variables from the largest published summary statistics of the oral lesion phenotype GWAS in UK Biobank (UKBB) and GERD GWAS. Then, we performed a causal inference analysis between GERD and common oral lesions by mendelian randomization (MR) analysis with the R package "TwoSampleMR". Results: We observed a significant causal relationship between GERD and several common oral lesion phenotypes (painful gums, loose teeth, toothache, and mouth ulcers). GERD showed a positive correlation with the occurrence of these oral lesions. After removing outlier SNPs via the MR-PRESSO package, our conclusions were still robust. Conclusion: Our findings provide the first evidence for a genetic causal effect of GERD on oral lesion pathogenesis. For patients with confirmed GERD, attention should be paid to taking interventions to prevent the occurrence of oral lesions.

Effects of injectable platelet rich fibrin on bone remodeling in combination with DBBM in maxillary sinus elevation: a randomized preclinical study.

OBJECTIVES: This study aims to assess the angiogenic and osteogenic capacity in rabbit sinus model grafted with Deproteinized bovine bone mineral (DBBM) particles soaked in injectable Platelet rich fibrin (iPRF), both of which interacted to form an integrated block. MATERIALS AND METHODS: Among sixteen rabbits, bilateral maxillary sinuses were randomly grafted with either DBBM containing iPRF (iPRF+DBBM group), or DBBM alone (DBBM group). After a 4 and 8-week healing period, animals were sacrificed for micro-CT, histological and immunofluorescence analyses, respectively. RESULTS: New bone formation in the iPRF+DBBM group was largely observed around the basal bone wall and Schneiderian membrane (SM), which further substitute the bone grafting material in a bidirectional remodeling pattern. Although the ultimate amount of bone volume was of no significant difference between two groups in radiographical image, the expression of ALP and TRAP staining were significantly higher in the experimental group with numerous vascular formations at 4th week. Moreover, the substitution rate of DBBM by new bone formation after 8 weeks was significantly higher in the experimental group. As a result, mature collagen fibers were detected in the larger amount of area in iPRF+DBBM group even at an early stage. CONCLUSION: iPRF+DBBM accelerated vascular formation, bone remodeling and substitution of bone graft materials at the early healing period, even though it failed to increase the bone volume in a long-term period. This integrated grafting biomaterial will have great potential in the application of sinus augmentation, which provides a favorable environment for early implant placement.

The sialylation profile of IgG determines the efficiency of antibody directed osteogenic differentiation of iMSCs by modulating local immune responses and osteoclastogenesis.

Antibody-mediated osseous regeneration (AMOR) has been proved as a promising strategy for osteogenic differentiation of induced pluripotent stem cells derived MSCs (iMSCs). The key characteristic of antibody that determines the AMOR potential is largely unknown. The glycosylation profile of immunoglobulin G (IgG) represents a key checkpoint that determines its effector functions. Herein, we modified the sialylation profile of BMP2 antibodies to investigate the effects of glycosylation on antibody-mediated osteogenic differentiation of iMSCs. We found that over-sialylated BMP2 antibodies stimulated the highest amount of new bone while those non- or low-sialylated led to bone porosity and collapse. The immune response aroused by BMP2 immune complexes (BMP2-ICs) was intensified by desialylation, which contributed to an environment that favored osteoclastogenesis while inhibited osteoblastogenesis. In vitro study further demonstrated that the osteogenic potential of BMP2-ICs was not significantly affected by the degree of sialylation. On the other hand, BMP2-ICs could stimulate osteoclastogenesis by binding FcγRs on preosteoclasts directly, which was significantly intensified by desialylation and attenuated by over-sialylation. Bone defects implanted with alginate microbeads loaded with iMSCs and over-sialylated antibodies showed more bone formation than those sites with non- or low sialylated antibodies. Taken together, our study demonstrated that sialylation profile is one of the traits that decide the AMOR potential of BMP2 antibodies. Enhancement of sialylation may be a promising strategy to optimize antibody for iMSCs application in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Antibody-mediated osseous regeneration (AMOR) is a promising strategy for bone tissue engineering that takes advantage of the specific reactivity of antibodies to sequester endogenous BMP2 and present it to osteoprogenitor cells. We previously demonstrated that BMP2 immune complex can drive iPSCs derived MSCs to osteogenic lineage. In this study, we analyze the effects of glycosylation profile on antibody directed osteogenic differentiation of iMSCs because glycosylation profile represents a key checkpoint that determines the effector functions of antibodies, and it is susceptible to variations in different clones. The results showed that sialylation profile is one of the traits that decides the AMOR potential of BMP2 antibody, and the enhancement of sialylation maybe a promising strategy to optimize antibodies for AMOR.

Study on the role of FoxO1 in the regulation of osteoblastic metabolism by 1,25(OH) 2 D 3 in a high glucose envi⁃ronment / 口腔疾病防治

Objective@#Yingying, Email: yywdentist@163.com, Tel: 86⁃28⁃85503579 【Abstract】 Objective To explore the effect of 1,25(OH) 2 D 3 on the regulation of bone metabolism in a high⁃glucose environment and to provide evidence for the possible regulatory mechanism of 1,25(OH) 2 D 3 on osteoblasts in a high⁃glu⁃ cose environment.@* Methods@#The osteoblast cell line MC3T3⁃E1 was cultured in 3 groups: ① control group, cultured in low⁃glucose (5.5 mmol/L) DMEM; ② high⁃glucose group: cultured in high⁃glucose (22 mmol/L) DMEM; ③ high⁃glu⁃ cose +1,25(OH) 2 D 3 group: high⁃glucose DMEM + 1,25(OH) 2 D 3 medium culture. The CCK⁃8 method was used to detect cell proliferation in each group; Annexin V and FITC apoptosis kits were used to detect apoptosis; Alizarin red was used to semiquantitatively analyze cell differentiation; qRT⁃PCR was used to detect forkhead transcription factor⁃1 (forkhead transcription factor 1, FoxO1) mRNA expression. Immunofluorescence was used to observe the changes in FoxO1 pro⁃ tein expression and its relative position in the nucleus.@* Results@#ence was used to observe the changes in FoxO1 pro⁃ tein expression and its relative position in the nucleus. Results Our analysis showed that compared with those in the control group, the osteoblast apoptosis and proliferation in the high⁃glucose group were improved, while differentiation was inhibited (P < 0.05); at the same time, the mRNA expression of FoxO1(P = 0.006) was reduced. The immunofluores⁃ cence results showed that more FoxO1 was inside the nucleus (P < 0.001). Compared with those in the high⁃glucose group, excessive proliferation was inhibited, apoptosis was reduced, and osteogenic differentiation was improved in the high⁃glucose +1,25(OH) 2 D 3 group (P < 0.05); furthermore, FoxO1 mRNA was decreased (P = 0.006), and the transfer of FoxO1 protein was blocked (P < 0.001).@* Conclusion @#re, FoxO1 mRNA was decreased (P = 0.006), and the transfer of FoxO1 protein was blocked (P < 0.001). Conclusion We found that 1,25(OH) 2 D 3 may prevent the transfer of FoxO1 to the cell nucleus, inhibit the abnormal proliferation and apoptosis of osteoblasts in a high⁃glucose environment, and re⁃ verse the inhibitory effect of high glucose on the differentiation of osteoblasts.

Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4.

Mesenchymal stem cells (MSCs) can attract host endothelial progenitor cells (EPCs) to promote vascularization in tissue-engineered constructs (TECs). Nevertheless, the underlying mechanism remains vague. This study is aimed at investigating the roles of CXCR2 and CXCR4 in the EPC migration towards MSCs. In vitro, Transwell assays were performed to evaluate the migration of EPCs towards MSCs. Antagonists and shRNAs targeting CXCR2, CXCR4, and JAK/STAT3 were applied for the signaling blockade. Western blot and RT-PCR were conducted to analyze the molecular events in EPCs. In vivo, TECs were constructed and subcutaneously implanted into GFP+ transgenic mice. Signaling inhibitors were injected in an orientated manner into TECs. Recruitment of host CD34+ cells was evaluated by immunofluorescence. Eventually, we demonstrated that CXCR2 and CXCR4 were both highly expressed in migrated EPCs and indispensable for MSC-induced EPC migration. CXCR2 and CXCR4 strongly correlated with each other in the way that the expression of CXCR2 and CXCR2-mediated migration depends on the activity of CXCR4 and vice versa. Further studies documented that both of CXCR2 and CXCR4 activated STAT3 signaling, which in turn regulated the expression of CXCR2 and CXCR4, as well as cell migration. In summary, we firstly introduced a reciprocal crosstalk between CXCR2 and CXCR4 in the context of EPC migration. This feedback loop plays critical roles in the migration of EPCs towards MSCs.

PPARγ and Its Ligands: Potential Antitumor Agents in the Digestive System.

Peroxisome proliferator-activated receptor γ (PPARγ) is a versatile member of the ligand-activated nuclear hormone receptor superfamily of transcription factors, with expression in several different cell lines, especially in the digestive system. After being activated by its ligand, PPARγ can suppress the growth of oral, esophageal, gastric, colorectal, liver, biliary, and pancreatic tumor cells, suggesting that PPARγ ligand is a potential anticancer agent in PPARγ-expressing tumors. This review highlights key advances in understanding the effects of PPARγ ligands in the treatment of tumors in the digestive system.

Perspectives on the toxicology of cadmium-based quantum dots.

As the number of applications of quantum dots (QDs) grows, the likelihood of exposure increases. Because these metals have the potential for detrimental environmental and health effects, concerns have been raised over our lack of understanding about the fate of these products. Among various types of QDs, cadmium-based quantum dots attract the greatest attention due to their wide applications. To properly assess the potential risk of cadmium-containing QDs, we summarize the current state of academic knowledge on the toxicity of cadmium-based QDs.

PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia: a case-control study in southwest China.

UNLABELLED: Our research aimed to look into the clinical traits and genetic mutations in sporadic non-syndromic anodontia and to gain insight into the role of mutations of PAX9, MSX1, AXIN2 and EDA in anodontia phenotypes, especially for the PAX9. MATERIAL AND METHODS: The female proband and her family members from the ethnic Han families underwent complete oral examinations and received a retrospective review. Venous blood samples were obtained to screen variants in the PAX9, MSX1, AXIN2, and EDA genes. A case-control study was performed on 50 subjects with sporadic tooth agenesis (cases) and 100 healthy controls, which genotyped a PAX9 gene polymorphism (rs4904210). RESULTS: Intra-oral and panoramic radiographs revealed that the female proband had anodontia denoted by the complete absence of teeth in both the primary and secondary dentitions, while all her family members maintained normal dentitions. Detected in the female proband were variants of the PAX9 and AXIN2 including A240P (rs4904210) of the PAX9, c.148C>T (rs2240308), c.1365A>G (rs9915936) and c.1386C>T (rs1133683) of the AXIN2. The same variants were present in her unaffected younger brother. The PAX9 variations were in a different state in her parents. Mutations in the MSX1 and EDA genes were not identified. No significant differences were found in the allele and genotype frequencies of the PAX9 polymorphism between the controls and the subjects with sporadic tooth agenesis. CONCLUSIONS: These results suggest that the association of A240P with sporadic tooth agenesis still remains obscure, especially for different populations. The genotype/phenotype correlation in congenital anodontia should be verified.

PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia: a case-control study in southwest China

Our research aimed to look into the clinical traits and genetic mutations in sporadic non-syndromic anodontia and to gain insight into the role of mutations of PAX9, MSX1, AXIN2 and EDA in anodontia phenotypes, especially for the PAX9. Material and Methods The female proband and her family members from the ethnic Han families underwent complete oral examinations and received a retrospective review. Venous blood samples were obtained to screen variants in the PAX9, MSX1, AXIN2, and EDA genes. A case-control study was performed on 50 subjects with sporadic tooth agenesis (cases) and 100 healthy controls, which genotyped a PAX9 gene polymorphism (rs4904210). Results Intra-oral and panoramic radiographs revealed that the female proband had anodontia denoted by the complete absence of teeth in both the primary and secondary dentitions, while all her family members maintained normal dentitions. Detected in the female proband were variants of the PAX9 and AXIN2 including A240P (rs4904210) of the PAX9, c.148C>T (rs2240308), c.1365A>G (rs9915936) and c.1386C>T (rs1133683) of the AXIN2. The same variants were present in her unaffected younger brother. The PAX9 variations were in a different state in her parents. Mutations in the MSX1 and EDA genes were not identified. No significant diferences were found in the allele and genotype frequencies of the PAX9 polymorphism between the controls and the subjects with sporadic tooth agenesis. Conclusions These results suggest that the association of A240P with sporadic tooth agenesis still remains obscure, especially for different populations. The genotype/phenotype correlation in congenital anodontia should be verified. .