Hochuekkito, a Kampo (traditional Japanese herbal) Medicine, Enhances Mucosal IgA Antibody Response in Mice Immunized with Antigen-entrapped Biodegradable Microparticles

The effect of oral administration of Hochuekkito (HET; Bu-Zhong-Yi-Qi-Tang in Chinese), a traditional Japanese herbal medicine, on mucosal IgA immune response was investigated. To induce the antigen-specific antibodies in mucosal site, ovalbumin (OVA)-entrapped biodegradable microparticles (OVA-microparticles) were used as an antigen. Mice were orally immunized with OVA-microparticles for 3 successive days with intragastric gavage. From 7 days after the onset of immunization, the mice were boosted twice a week with the same antigen for 2 weeks. HET or water alone was orally administered to the mice via the intragastric route from 7 days before to 27 days after the onset of immunization. Although no significant change in total secretory IgA antibody level was observed in intestinal and nasal washes, OVA-specific IgA titers in intestinal washes were significantly enhanced by oral administration of HET. When lymphocytes from spleen, peripheral blood and Payer's patches were investigated for cytokines production, it was found that the IFN-γ secretion from the lymphocytes was increased by the administration of HET. Microarray analysis of Peyer's patch cells revealed enhanced expression of L-selectin gene. The increase of L-selectin positive cells in B lymphocytes fraction was observed in Peyer's patch cells and peripheral blood mononuclear cells by flow cytometry. These results suggest that the enhanced IFN-γ secretion and increased population of L-selectin positive B lymphocytes by orally administered HET may partly contribute to enhancement of IgA immune response against intestinal antigens, and orally administered HET may strengthen defensive systems against various pathogens and food antigens in intestine

Regression of glomerulosclerosis in response to transient treatment with angiotensin II blockers is attenuated by blockade of matrix metalloproteinase-2

Understanding mechanisms that contribute to the regression of glomerulosclerosis is important for developing new strategies to treat chronic kidney disease. We reported that transient high-dose treatment with an angiotensin receptor blocker causes regression of renal arteriolar hypertrophy and hypertension in spontaneously hypertensive rats. To extend those findings to another form of kidney disease, we examined the short- and long-term effects of transient high-dose angiotensin receptor blocker treatment in a mouse model of adriamycin-induced glomerulosclerosis. A 2-week course of candesartan caused a dose-dependent regression of established glomerulosclerotic lesions sustained for over 6 months following cessation of treatment. Highly sensitive in situ zymography and activity assays showed that glomerular matrix metalloproteinase (MMP)-2 activity was increased after high-dose angiotensin blocker therapy. Treatment of cultured podocytes with candesartan resulted in an increase in MMP-2 activity. The regression of glomerulosclerosis was partially attenuated in mice pretreated with the MMP inhibitor doxycycline, as well as in MMP-2 knockout mice. Our results suggest that transient high-dose angiotensin receptor blocker treatment effectively induced sustained regression of glomerulosclerosis by a mechanism mediated, in part, by changes in MMP-2 activity

Fracture origin and crack propagation of CAD/CAM composite crowns by combining of in vitro and in silico approaches

Purpose: Fractographic analysis has been used to investigate the fracture behavior of Computer-aided design/computer-aided manufacturing (CAD/CAM) composite crowns by subjecting them to compression tests. However, it is difficult to investigate details of the fracture, including its initiation and propagation, using in vitro tests. The aim of this study was to determine the fracture origins and the order of crack initiation of CAD/CAM composite crowns using in silico nonlinear dynamic finite element analysis (FEA). Material and methods: The following materials were used: Cerasmart (CS), Katana Avencia Block (KA), and Shofu Block HC (HC) as CAD/CAM crowns, Panavia SA Cement Plus (SA) as a luting material, and Clearfil DC Core Plus (DC) as an abutment. The elastic moduli and fracture strain of each material were obtained from the stress–strain curve of in vitro three-point bending tests. The fracture origins and order of crack initiation of the materials were determined by in silico nonlinear dynamic compression analysis. Load-displacement curves were statistically compared with the results of the in vitro compression tests (Pearson's correlation test, α = 0.05). Results: The nonlinear dynamic FEA demonstrated that crack initiation was primarily observed near the lingual side of the CAD/CAM crowns and immediately propagated to the central fossa. The models were fractured following the in vitro fracture strains, showing the same order for the products tested (CS/KA/HC, SA, and DC). Load-displacement curves with the use of CS, KA, and HC were significantly correlated to the corresponding in vitro compression tests results (CS: r = 0.985, p < 0.05, KA: r = 0.987, p < 0.05, and HC: r = 0.997, p < 0.05). Conclusions: The in silico model established in this study clarified the crack initiation of the CAD/CAM composite crowns and the order of crack initiation among the investigated products, suggesting that the present approach is useful for analyzing the fracture behavior of CAD/CAM composite crowns in detail.Yamaguchi S., Katsumoto Y., Hayashi K., et al. Fracture origin and crack propagation of CAD/CAM composite crowns by combining of in vitro and in silico approaches. Journal of the Mechanical Behavior of Biomedical Materials 112, 104083 (2020); https://doi.org/10.1016/j.jmbbm.2020.104083