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A Stealthiness Evaluation of Main Chain Carboxybetaine Polymer Modified into Liposome
No full textBackground: Acrylamide polymers with zwitterionic carboxybetaine (CB) side groups have attracted attention as stealth polymers that do not induce antibodies when conjugated to proteins. However, they induce antibodies when modified onto liposomes. We hypothesized that antibodies are produced against polymer backbones rather than CB side groups. Objectives: In this study, we designed and synthesized a polymer employing CB in its main chain, poly(N-acetic acid-N-methyl-propyleneimine) (PAMPI), and evaluated the blood retention of PAMPI-modified liposomes in mice. Results: The non-fouling nature of PAMPI-modified liposomes estimated from serum protein adsorption was found to be not inferior to PCB- and PEG-modified liposomes. However, to our surprise, the PAMPI-modified liposomes showed an instantaneous clearance less than 1 h post-injection, comparable to the naked liposomes. Conclusions: The extent of the blood retention of polymer-modified liposomes cannot be predicted by their susceptibility to serum protein adsorption and semi-flexible conformation.journal articl
Attitudes toward smoking cessation according to smoking status among dentists in the Aichi Dental Association in Japan
Get PDFIntroduction: The prevalence of smoking, including heated tobacco products (HTPs), among Japanese dentists was reported to be 16.5%, significantly higher than that among Japanese physicians and United States dentists. However, large-scale studies on smoking cessation implementation based on dentists' smoking status and perceptions since the introduction of HTPs are lacking. Therefore, we aimed to investigate and assess dentists' attitudes toward smoking, including HTP use and smoking cessation, according to smoking status.
Methods: A self-administered questionnaire comprising six major items was mailed to 3883 dentists who were members of the Aichi Dental Association in August 2019. The primary outcome was smoking cessation status. The secondary outcome was the impact of smoking on intervention for smoking cessation. This study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
Results: Among the 1317 (42%) dentists analyzed, men were more positive toward smoking than women. Current and former smokers were more positive about smoking than never smokers/users, regardless of the tobacco product type. Additionally, the current smoker group using conventional cigarettes was less likely to ask for their patients' smoking status than the never smoker group. Furthermore, the current smoker (OR=2.0; 95% CI: 1.3–3.1 vs never smoker) and HTP user (OR=1.9; 95% CI: 1.2–3.1 vs never user) groups were less likely to engage in smoking cessation than the never smoker/user groups, regardless of the tobacco product type.
Conclusions: Since the smoking status of dentists affects the implementation of smoking cessation interventions, it is crucial to encourage them to quit using all tobacco products to promote smoking cessation interventions in dental practice. Additionally, providing proper smoking prevention education to dentists is an important task.doctoral thesi
Fabrication of Mie-resonant silicon nanoparticles using laser annealing for surface-enhanced fluorescence spectroscopy
Get PDFSilicon nanostructures with unique Mie resonances have garnered considerable attention in the field of nanophotonics. Here, we present a simple and efficient method for the fabrication of silicon (Si) nanoparticle substrates using continuous-wave (CW) laser annealing. The resulting silicon nanoparticles exhibit Mie resonances in the visible region, and their resonant wavelengths can be precisely controlled. Notably, laser-annealed silicon nanoparticle substrates show a 60-fold enhancement in fluorescence. This tunable and fluorescence-enhancing silicon nanoparticle platform has tremendous potential for highly sensitive fluorescence sensing and biomedical imaging applications.journal articl
ALLO-1- and IKKE-1-dependent positive feedback mechanism promotes the initiation of paternal mitochondrial autophagy
Get PDFAllophagy is responsible for the selective removal of paternally inherited organelles, including mitochondria, in Caenorhabditis elegans embryos, thereby facilitating the maternal inheritance of mitochondrial DNA. We previously identified two key factors in allophagy: an autophagy adaptor allophagy-1 (ALLO-1) and TBK1/IKKε family kinase IKKE-1. However, the precise mechanisms by which ALLO-1 and IKKE-1 regulate local autophagosome formation remain unclear. In this study, we identify two ALLO-1 isoforms with different substrate preferences during allophagy. Live imaging reveals a stepwise mechanism of ALLO-1 localization with rapid cargo recognition, followed by ALLO-1 accumulation around the cargo. In the ikke-1 mutant, the accumulation of ALLO-1, and not the recognition of cargo, is impaired, resulting in the failure of isolation membrane formation. Our results also suggest a feedback mechanism for ALLO-1 accumulation via EPG-7/ATG-11, a worm homolog of FIP200, which is a candidate for IKKE-1-dependent phosphorylation. This feedback mechanism may underlie the ALLO-1-dependent initiation and progression of autophagosome formation around paternal organelles.journal articl
Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis
Get PDFPrimary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.journal articl
Inactivation of siderophore iron-chelating moieties by the fungal wheat root symbiont Pyrenophora biseptata
Get PDFWe investigated the ability of four plant and soil-associated fungi to modify or degrade siderophore structures leading to reduced siderophore iron-affinity in iron-limited and iron-replete cultures. Pyrenophora biseptata, a melanized fungus from wheat roots, was effective in inactivating siderophore iron-chelating moieties. In the supernatant solution, the tris-hydroxamate siderophore desferrioxamine B (DFOB) underwent a stepwise reduction of the three hydroxamate groups in DFOB to amides leading to a progressive loss in iron affinity. A mechanism is suggested based on the formation of transient ferrous iron followed by reduction of the siderophore hydroxamate groups during fungal high-affinity reductive iron uptake. P. biseptata also produced its own tris-hydroxamate siderophores (neocoprogen I and II, coprogen and dimerum acid) in iron-limited media and we observed loss of hydroxamate chelating groups during incubation in a manner analogous to DFOB. A redox-based reaction was also involved with the tris-catecholate siderophore protochelin in which oxidation of the catechol groups to quinones was observed. The new siderophore inactivating activity of the wheat symbiont P. biseptata is potentially widespread among fungi with implications for the availability of iron to plants and the surrounding microbiome in siderophore-rich environments.journal articl
Combined visual and quantitative assessment of somatostatin receptor scintigraphy for staging and restaging of neuroendocrine tumors
Get PDFPurpose: Somatostatin receptor scintigraphy (SRS) using 111In-DTPA-DPhe1-octreotide (pentetreotide) has become an integral part of neuroendocrine neoplasm management. The lack of precise quantification is a disadvantage of SRS. This study aimed to adapt the standardized uptake value (SUV) to SRS, establish the SUV range for physiological uptake in the liver, kidney, and spleen, and elucidate the utility of combined visual and quantitative SRS assessment for staging and restaging of neuroendocrine tumors (NETs).
Materials and methods: This study included 21 patients with NETs who underwent 111In-pentetreotide SRS. The SUV of physiological and pathological uptake was calculated using bone single-photon emission computed tomography (SPECT) quantitative analysis software (GI-BONE). For visual analysis, the primary and metastatic lesions were scored visually on planar and SPECT images using a five-point scale. We assessed the relationships between the SUVs of the liver, kidney, and spleen in the dual phase, and among quantitative indices, visual score, and pathological lesions classification.
Results: Sixty-three NEN lesions were evaluated. The mean±standard deviation maximum SUVs (SUVmax) were liver: 4 h, 2.6±1.0; 24 h, 2.2±1.0; kidney: 4 h, 8.9±1.8; 24 h, 7.0±2.0; and spleen; 4 h, 11.3±4.5; 24 h, 11.5±7.6. Higher SUVmax was significantly associated with higher visual scores on dual-phase SPECT (4 h, p <0.001; 24 h, p <0.001) (4 h: scores 3 and 4, p <0.05; scores 3 and 5: p <0.01; scores 4 and 5: p <0.01; 24 h: scores 3 and 4, p=0.0748; scores 3 and 5: p <0.01; scores 4 and 5: p <0.01).
Conclusion: We adapted the SUV to SRS and established the range of SUV for physiological uptake in the liver, kidney, and spleen. Combined visual and quantitative assessment is useful for imaging individual lesions in greater detail, and may serve as a new tumor marker of SRS for staging and restaging of NETs.journal articl