Improvement of acid resistance of Zn-doped dentin by newly generated chemical bonds

Dental caries, the world's most prevalent infectious disease, is caused by the diffusion of hydroxyl ions into tooth structures. To prevent dental caries, the application of fluoride (F) and zinc (Zn) ions to teeth surfaces are potential effective measures. In this study, The ionic influence, especially the chemical bond of F and Zn, on the acid resistance of dentin were investigated by particle induced X-ray / gamma-ray emission, X-ray diffraction, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy. The results showed Zn was distributed in the limited surface layer of dentin without altering its crystal structure. From the Zn K edge extended X-ray absorption fine structure, Zn incorporated into dentin was surrounded by oxygen and demonstrated four-fold coordination. The bond length and chemical state of Zn–O in Zn doped dentin suggested newly generated Zn–O covalent bond, which may improve acid resistance of dentin. This study showed that the atomic and molecular structures, such as the molecular distances and chemical state, influenced acid resistance of teeth, emphasizing the validity of chemical state analysis for understanding properties in biomaterials.Naito K., Kuwahara Y., Yamamoto H., et al. Improvement of acid resistance of Zn-doped dentin by newly generated chemical bonds. Materials and Design, 215, 110412. https://doi.org/10.1016/j.matdes.2022.110412

Structural insights into the HBV receptor and bile acid transporter NTCP

B型肝炎ウイルスの受容体“胆汁酸輸送体”の立体構造を解明. 京都大学プレスリリース. 2022-05-18.Roughly 250 million people are infected with hepatitis B virus (HBV) worldwide, and perhaps 15 million also carry the satellite virus HDV, which confers even greater risk of severe liver disease. Almost ten years ago the HBV receptor was identified as NTCP (sodium taurocholate co-transporting polypeptide), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large (L) protein. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria, and these models with ten transmembrane helices are believed to resemble strongly both NTCP and ASBT. Using cryo-electron microscopy we have solved the structure of NTCP bound to an antibody, clearly showing the transporter has no equivalent to the first transmembrane helix of other SLC10 models, leaving the N-terminus exposed on the extracellular face. Comparison of the different structures indicates a common mechanism of bile acid transport, but the NTCP structure also displays a pocket formed by residues known to interact with preS1, presenting new and enticing opportunities for structure-based drug design

In-air micro-proton-induced x-ray/gamma-ray emission analysis of the acid resistance of root dentin after applying fluoride-containing materials incorporating calcium

This study employed an in-air micro-proton-induced X-ray/gamma-ray emission system to assess the effectiveness of fluoride-containing materials (FCMs) incorporating calcium in preventing root caries. Dentin surfaces of human third molars were coated with one of three FCMs: fluoride-releasing glass-ionomer cement (F7) and experimental materials in which half (P1) or all (P2) of the strontium in F7 was replaced with calcium. Dentin without FCM coating served as the control. Specimens were immersed in saline at 37°C for 1 month, sectioned, and then demineralized. Calcium loss after demineralization was lower in the Ca-substituted groups than in the Ca-unsubstituted groups (p<0.05). Calcium loss was negatively correlated with fluoride uptake (p<0.01). In the F7, P1, and P2 groups, the retraction of the dentin surface was significantly suppressed as compared with the control group. FCMs incorporating calcium improved the acid resistance of root dentin and could help prevent root caries.Yagi K., Uemura R., Yamamoto H., et al. In-air micro-proton-induced x-ray/gamma-ray emission analysis of the acid resistance of root dentin after applying fluoride-containing materials incorporating calcium. Dental Materials Journal 40, 1142 (2021); https://doi.org/10.4012/dmj.2020-273

Morphological Analyses of Effects of Endodontic Irrigant Solutions Using a Root Canal Model and an Immersion Model

Objective. This study aimed to compare an experimental model simulating clinical root canal irrigation (root canal model) with a conventional experimental model immersing dentin sample to irrigants (immersion model) to evaluate removal of the smear layer and decalcification of the root canal dentin using sodium hypochlorite (NaOCl) and two different concentrations of ethylenediaminetetraacetic acid (EDTA) solution. Materials and Methods. Forty-five single-rooted extracted human teeth were prepared using a Ni–Ti rotary file. EDTA, NaOCl, and citric acid were used in the root canal models and the immersion models. After the irrigation protocol, root canal surfaces were observed under scanning electron microscopy. Residual smear and decalcification of the root canal dentin were evaluated objectively by measuring the percentage of the area occupied by visible dentin tubules, the number of visible dentin tubules, and the mean area of a visible single dentin tubule. Results. Root canal and immersion models with the same irrigation protocol showed significantly different results for smear residues and decalcification of root canal dentin. In the root canal model, neither different EDTA concentrations nor the order of EDTA and NaOCl applications significantly impacted smear residues or decalcification of root canal dentin. Furthermore, no erosion of the root canal dentin surface was observed in any experimental groups in the root canal model using EDTA and NaOCl compared to intact dentin. Conclusions. Experimental design affected results for residual smear layer and decalcification of root canal dentin. The order of EDTA and NaOCl use and the concentration of EDTA did not affect results. EDTA and NaOCl irrigation did not cause erosion in the root canal model in this study

Intracellular Major Histocompatibility Complex Class II and C-X-C Motif Chemokine Ligand 10-Expressing Neutrophils Indicate the State of Anti-Tumor Activity Induced by <i>Bacillus Calmette–Guérin</i>

(1) Background: Inflammatory responses induce the formation of both anti-tumor and pro-tumor neutrophils known as myeloid-derived suppressor cells (MDSCs). Intermittent intravesical infusion of Bacillus Calmette–Guérin (BCG) is an established cancer immunotherapy for non-muscle-invasive bladder cancer (NMIBC). However, the types of neutrophils induced via the inflammatory response to both tumor-bearing and BCG remain unclear. (2) Methods: We therefore analyzed neutrophil dynamics in the peripheral blood and urine of patients with NMIBC who received BCG therapy. Further, we analyzed the effects of BCG in a mouse intraperitoneal tumor model. (3) Results: BCG therapy induced the formation of CXCL10 and MHC class II-positive neutrophils in the urine of patients with NMIBC but did not induce MDSC formation. CXCL10- and MHC class II-expressing neutrophils were detected in peritoneal exudate cells formed after BCG administration. Partial neutrophil depletion using an anti-Ly6G antibody suppressed the upregulation of CXCL10 and MHC class II in neutrophils and reversed the anti-tumor activity of BCG in mouse models. (4) Conclusions: These results indicated that intracellular MHC class II- and CXCL10-expressing neutrophils indicate the state of anti-tumor activity induced via BCG. The status of neutrophils in mixed inflammation of immunosuppressive and anti-tumor responses may therefore be useful for evaluating immunological systemic conditions

Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke

Abstract Background Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively