Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report

BACKGROUND: Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. CASE PRESENTATION: A 14-year-old Chinese boy suffering from β–thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, and depapillation of tongue indicating an underlying condition of anemia. The poor oral condition due to topical and systemic immunosuppressants was seriously aggravated, and rampant caries developed rapidly, affecting all newly erupted, permanent teeth. The teeth were hypersensitive and halitosis was apparent. Strategies for oral health education and diet modification were given to the patient. Xylitol chewing gum was used to stimulate saliva flow to promote remineralization of teeth. Silver diamine fluoride was topically applied to arrest rampant caries and to relieve pain from hypersensitivity. Carious teeth with pulpal involvement were endodontically treated. Stainless steel crowns were provided on molars to restore chewing function, and polycarbonate crowns were placed on premolars, upper canines and incisors. CONCLUSION: This case report demonstrates success in treating a young teenager with severe rampant dental decay by contemporary caries control and preventive strategy

“Hot Edges” in Inverse Opal Structure Enable Efficient CO2 Electrochemical Reduction and Sensitive in-situ Raman Characterization

Conversion of CO 2 into fuels and chemicals via electroreduction has attracted significant interest. Via mesostructure design to tune the electric field distribution in the electrode, it is demonstrated that the Cu-In alloy with an inverse opal (CI-1-IO) structure provides efficient electrochemical CO 2 reduction and allows for sensitive detection of the CO 2 reduction intermediates via surface-enhanced Raman scattering. The significant enhancement of Raman signals of the intermediates on the CI-1-IO surface can be attributed to electric field enhancement on the "hot edges" of the inverse opal structure. Additionally, a highest CO 2 reduction faradaic efficiency (FE) of 92% (sum of formate and CO) is achieved at-0.6 V vs. RHE on the CI-1-IO electrode. The diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) results show that the Cu-In alloy with an inverse opal structure has faster adsorption kinetics and higher adsorption capacity for CO 2. The "hot edges" of the bowl-like structure concentrate electric fields, due to the high curvature, and also concentrate K + on the active sites, which can lower the energy barrier of the CO 2 reduction reaction. This research provides new insight into the design of materials for efficient CO 2 conversion and the detection of intermediates during the CO 2 reduction process. </p

Linking deeply-sourced volatile emissions to plateau growth dynamics in southeastern Tibetan Plateau

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Zhang, M., Guo, Z., Xu, S., Barry, P. H., Sano, Y., Zhang, L., Halldorsson, S. A., Chen, A.-T., Cheng, Z., Liu, C.-Q., Li, S.-L., Lang, Y.-C., Zheng, G., Li, Z., Li, L., & Li, Y. Linking deeply-sourced volatile emissions to plateau growth dynamics in southeastern Tibetan Plateau. Nature Communications, 12(1), (2021): 4157, https://doi.org/10.1038/s41467-021-24415-y.The episodic growth of high-elevation orogenic plateaux is controlled by a series of geodynamic processes. However, determining the underlying mechanisms that drive plateau growth dynamics over geological history and constraining the depths at which growth originates, remains challenging. Here we present He-CO2-N2 systematics of hydrothermal fluids that reveal the existence of a lithospheric-scale fault system in the southeastern Tibetan Plateau, whereby multi-stage plateau growth occurred in the geological past and continues to the present. He isotopes provide unambiguous evidence for the involvement of mantle-scale dynamics in lateral expansion and localized surface uplift of the Tibetan Plateau. The excellent correlation between 3He/4He values and strain rates, along the strike of Indian indentation into Asia, suggests non-uniform distribution of stresses between the plateau boundary and interior, which modulate southeastward growth of the Tibetan Plateau within the context of India-Asia convergence. Our results demonstrate that deeply-sourced volatile geochemistry can be used to constrain deep dynamic processes involved in orogenic plateau growth.This work was supported by China Seismic Experimental Site (CSES) (2019CSES0104), the Strategic Priority Research Program (B) of Chinese Academy of Sciences (XDB26000000), the National Key Research and Development Program of China (2020YFA0607700), the National Natural Science Foundation of China (41930642, 41602341, 41772355, and 41702361), the Second Tibetan Plateau Scientific Expedition and Research Program (STEP) (2019QZKK0702), and the United Laboratory of High-Pressure Physics and Earthquake Science (2019HPPES02). P.H.B. was supported by the US National Science Foundation EAR Grant 1144559 during a portion of this work

5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation

While it is well established that treatment of cancer patients with 5-Fluorouracil (5-FU) can result in immune suppression, the exact function of 5-FU in the modulation of immune cells has not been fully established. We found that low dose 5-FU selectively suppresses TH17 and TH1 cell differentiation without apparent effect on Treg, TH2, and significantly suppresses thymidylate synthase (TS) expression in TH17 and TH1 cells but has a lesser effect in tumor cells and macrophages. Interestingly, the basal expression of TS varies significantly between T helper phenotypes and knockdown of TS significantly impairs TH17 and TH1 cell differentiation without affecting the differentiation of either Treg or TH2 cells. Finally, low dose 5-FU is effective in ameliorating colitis development by suppressing TH17 and TH1 cell development in a T cell transfer colitis model. Taken together, the results highlight the importance of the anti-inflammatory functions of low dose 5-FU by selectively suppressing TH17 and TH1 immune responses

Assembly of Inflammation-Related Genes for Pathway-Focused Genetic Analysis

Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the Ingenuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP) arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs) and African (21,542 SNPs) populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and associated subpathways can facilitate comprehensive inflammation pathway- focused association analyses

Biochemical modulation of mandibular distraction osteogenesis

published_or_final_versionDentistryDoctoralDoctor of Philosoph

B7-H3 and 4-1BBL Cooperatively Enhance the Antitumor Response of CD8 T Cells in Oral Cancer

The aim of this study was to enhance the antitumor immunity of CD8 T cells directed against human oral cancer using B7-H3 and 4-1BBL gene transfer. Recombinant replication-defective adenovirus 5 (Adv) expressing human 4-1BBL, B7-H3 or 4-1BBUB7-H3 was constructed using the two-plasmid rescue method. Primary human oral cancer cell vaccines (OCV) were prepared by treating cells with 20 mu g/ml mitomycin-C after primary human oral cancer cells were infected with Adv transduced with 4-1BBL, B7-H3, 4-1BBUB7-H3 or control Adv. Then, autologous, purified CD8 T cells were stimulated by coculture with OCV for 4 days. At the end of the culture, CD8 T cell activation was evaluated by ELISA to assay the production of IFN gamma and IL-2 in the culture supernatants. Cytotoxic CD8 T cell effector function was analyzed by a 51Chromium (Cr)-release assay, and CD8 T cell proliferation was evaluated by flow cytometry and Cell Counting Kit-8 (CCK-8) assays. Primary human oral cancer cells expressed low levels of B7-H3 and 4-1BBL and weakly stimulated autologous T cells. The primary human oral cancer cell vaccine transduced with the combination of 4-1BBL with B7-H3 retroviruses resulted in significantly enhanced CD8 T cell activation and proliferation. This was associated with increased IFN gamma and IL-2 production by CD8 T cells and improved CD8 T cell proliferation. CD8 T cells stimulated with the autologous B7-3/4-1BBL primary human oral cancer cell vaccine efficiently killed the autologous parental B7-H3/4-1BBL primary human oral cancer cells. Strong CD8 T cell activation, proliferation and longer survival time could be obtained by this vaccine. These data provide a mechanism for developing tumor vaccines using modified tumor cells in patients with oral cancer

Human beta-defensin-3 (hBD-3) upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance lymphatic invasion of oral squamous cell carcinoma

Objective. In this study, the hypothesis that hBD-3 is upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance metastasis in oral squamous cell carcinoma (OSCC) was tested. Study design. hBD-3 expression in human tissue specimens was evaluated by RT-qPCR and immunohistochemical staining. The presence of hBD-3 peptide in the culture supernatants of each type of treated cells was evaluated by enzyme-linked immunosorbent assay. The chemotaxis response to LPS or hBD-3 protein of SCC-25 cells or siRNA-hBD-3 transfected cells were also measured by chemotaxis assay. Paired, 2-tailed Student t test and analysis of variance was used to assess the statistical significance between 2 groups or many groups. Results. hBD-3 is highly expressed and associated with lymphatic invasion of OSCC. hBD-3 expression and EGFR phosphorylation were markedly upregulated when SCC-25 cells were treated with LPS. When SCC-25 cells were preincubated with EGFR inhibitor or TLR4-neutralizing Ab before LPS stimulation, a decrease in the expression of hBD-3 was observed. hBD-3 markedly enhanced cancer metastasis, and the chemotaxis response to LPS of SCC-25 cells was partly blocked by siRNA target hBD-3. Conclusion. These findings indicate that hBD-3 is upregulated by LPS via EGFR signaling pathways to enhance lymphatic invasion of OSCC. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 112: 616-625