Treatment resistance of rheumatoid arthritis relates to infection of periodontal pathogenic bacteria: a case-control cross-sectional study

Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are involved in the pathogenesis of RA via citrullinated proteins. Smoking has also been shown to be involved in the pathogenesis of RA; however, the extent of this involvement is still poorly understood. In addition, RA and polymyalgia rheumatica (PMR) are sometimes difficult to differentiate; however, the relationship between PMR and the factors from smoking and periodontal bacteria is unclear. The aim of this study was to clarify the relationship between periodontal pathogenic bacterial infections and smoking in patients with RA or PMR. This case-control study included 142 patients with untreated RA or PMR. This study evaluated the serum antibody titers against periodontal pathogenic bacterial antigens and an anti-citrullinated peptide antibody (ACPA). In patients with RA, the relationship between antibody titers and disease activity of RA and response after 3 months of treatment was also investigated. Additionally, the effects of smoking were evaluated. Although there was no significant difference in serum antibody titer against periodontal pathogenic bacteria between the ACPA-positive RA group and the ACPA-negative PMR group, we found an association between the elevated antibody titer against Pg and the degree of ACPA value, especially between negative group and high-value positive group (>= 100 U/mL). The antibody titers against Aa and Pg did not differ depending on disease activity score 28 (DAS28) at baseline; however, patients with high antibody titers had poor RA therapeutic response as judged by DAS28 after 3 months. We could not find any association between smoking and any of these parameters. Periodontal pathogenic bacteria, especially Pg, are associated with elevated ACPA levels. Our findings suggest that Pg and Aa infections interfere with the therapeutic response of RA

Narrow-band UVB suppresses nasal symptom and H1R mRNA

Background: Phototherapy with narrow-band ultraviolet B (narrow-band UVB) is clinically effective treatment for atopic dermatitis. In the present study, we examined the effects of intranasal irradiation with narrow-band UVB on nasal symptom, upregulation of histamine H1 receptor (H1R) gene expression and induction of DNA damage in the nasal mucosa of allergic rhinitis (AR) model rat. Methods: AR model rats were intranasally irradiated with 310 nm of narrow-band UVB. Nasal mucosal levels of H1R mRNA were measured using real-time quantitative reverse transcriptase (RT)-PCR. DNA damage was evaluated using cyclobutane pyrimidine dimer (CPD) immunostaining. Results: In toluene 2, 4-diisocyanate (TDI)-sensitized rats, TDI provoked sneezes and H1R gene expression in the nasal mucosa. Intranasal pre-irradiation with 310 nm narrow-band UVB at doses of 600 and 1400, but not 200 mJ/cm2 significantly inhibited the number of sneezes and upregulation of H1R gene expression provoked by TDI. CPD-positive cells appeared in the nasal mucosa after intranasal narrow-band UVB irradiation at a dose of 1400, but not 200 and 600 mJ/cm2. The suppression of TDI-provoked sneezes and upregulation of H1R gene expression lasted 24 h, but not 48 h, after narrow-band UVB irradiation with a dose of 600 mJ/cm2. Conclusions: Intranasal pre-irradiation with narrow-band UVB dose-dependently inhibited sneezes and upregulation of H1R gene expression of the nasal mucosa in AR model rats, suggesting that the inhibition of nasal upregulation of H1R gene expression suppressed nasal symptom. The suppression after narrow-band UVB irradiation at a dose of 600 mJ/cm2 was reversible without induction of DNA damage. These findings indicated that low-dose narrow-band UVB phototherapy could be effectively and safely used for AR treatment in a clinical setting

Evaluation of the simulator with automatic irrigation control system designed for countermeasures of internal contamination in dental unit water lines

The prevention of nosocomial infections is an imperative task. The dental chair unit (DCU) is an indispensable device used in dental treatment. However, it is known that the dental unit water line (DUWL) can become contaminated with biofilm, consisting mainly of heterotrophic bacteria (HB). Recently, the International Organization for Standardization specified the methods for testing DUWL contamination management. On these grounds, a simulator reproducing DUWL was prepared to standardize the examination method of the DUWL contamination. Objectives To evaluate the reproducibility of the DUWL simulator, monitor the DUWL contamination states, and test the efficacy of a commercial decontaminant for DUWL. Methods The DUWL simulator was assembled by a DCU manufacturing company. The simulator's DUWL was filled with tap water (TW), and left for approximately one year. Neutral electrolyzed water (NEW) was used as a decontaminant for DUWL. Both TW and NEW were passed through DUWL in a timely manner simulating daily dental treatment. Water was sampled from the air turbine hand piece weekly for 4 weeks and used for HB culture. Contamination status was evaluated by measuring bacterial adenosine triphosphate release and by culturing on Reasoner's 2A medium. Results The DUWL released contaminated water had a bacterial count of over 6 × 104 cfu/mL. After passing NEW through DUWL for 1 week, the count drastically decreased to its basal level and remained steady for 4 weeks. However, TW showed no effect on DUWL decontamination throughout the examination periods. Conclusions The DUWL simulator could be useful to examine the efficacy of the decontaminant for DUWL and development of new methods in DUWL contamination management

Suppression of HBV replication by the expression of nickase-and nuclease dead-Cas9

Kurihara, T., Fukuhara, T., Ono, C. et al. Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9. Sci Rep 7, 6122 (2017). https://doi.org/10.1038/s41598-017-05905-

Escape fraction of ionizing photons from high-redshift galaxies in cosmological SPH simulations

Combing the three-dimensional radiative transfer (RT) calculation and cosmological SPH simulations, we study the escape fraction of ionizing photons (f_esc) of high-redshift galaxies at z=3-6. Our simulations cover the halo mass range of M_h = 10^9 - 10^12 M_sun. We postprocess several hundred simulated galaxies with the Authentic Radiative Transfer (ART) code to study the halo mass dependence of f_esc. In this paper, we restrict ourselves to the transfer of stellar radiation from local stellar population in each dark matter halo. We find that the average f_esc steeply decreases as the halo mass increases, with a large scatter for the lower mass haloes. The low mass haloes with M_h ~ 10^9 M_sun have large values of f_esc (with an average of ~ 0.4), whereas the massive haloes with M_h ~ 10^11 M_sun show small values of f_esc (with an average of ~ 0.07). This is because in our simulations, the massive haloes show more clumpy structure in gas distribution, and star-forming regions are embedded inside these clumps, making it more difficult for the ionizing photons to escape. On the other hand, in low mass haloes, there are often conical regions of highly ionized gas due to the shifted location of young star clusters from the center of dark matter halo, which allows the ionizing photons to escape more easily than in the high-mass haloes. By counting the number of escaped ionizing photons, we show that the star-forming galaxies can ionize the intergalactic medium at z=3-6. The main contributor to the ionizing photons is the haloes with M_h < 10^10 M_sun owing to their high f_esc. The large dispersion in f_esc suggests that there may be various sizes of H{\sc ii} bubbles around the haloes even with the same mass in the early stages of reionization. We also examine the effect of UV background radiation field on f_esc using simple, four different treatment of UV background.Comment: 13 pages, 13 figures, accepted for publication in MNRAS, A full resolution version is available at http://www.ccs.tsukuba.ac.jp/Astro/Members/yajima/Yajima2010.pd

Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction

Measuring the sorting effect of migration on spatial wage disparities

経済学 / EconomicsObserved spatial wage disparities reflect not only disparities in regional productivity but also an uneven geographical distribution of heterogeneous worker skills. We measure spatial skill disparities in Japan and evaluate how migration contributes to these disparities. For this purpose, we regress the individual wage on the residential region dummy variables and a series of individual characteristics to decompose the wage into regional productivity and the workers\u27 skills. The estimation illustrates that by removing the skill heterogeneities, the productivity disparity is approximately half of the observed wage disparity. Workers living in metropolitan areas have 9.7% higher skills than those in nonmetropolitan areas on average. The spatial skill disparity that stems from individuals\u27 hometowns is approximately 4.2%. Hence, migration increases the spatial skill disparity from 4.2% to 9.7%, which is an increase of 5.5 percentage points. Furthermore, we investigate migration effects in terms of the workers\u27 characteristics and find that most sorting effects of migration come from highly educated and regularly employed male workers.JEL Classification Codes: R23, J31, J61, R12http://www.grips.ac.jp/list/jp/facultyinfo/okamoto_ryosuke

Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer

Background The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors. Materials and methods A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed. Results TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor. Conclusion Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance