Maturation-associated changes in the non-specific immune response against Flavobacterium psychrophilum in Ayu Plecoglossus altivelis

In this study, we investigated maturation-associated changes in non-specific immune responses of ayu against Flavobacterium psychrophilum. The gonadosomatic index was minimum on 16 June, began to increase on 17 July, and reached the maximum value during August. The highest phagocytic rate (16.3%) was observed on 16 June, which decreased significantly to 5.6% on 26 August. The number of viable bacteria after the serum treatment was highest during August, suggesting that bactericidal activity of the serum decreased along with the sexual maturation. Gene expression levels of interleukin-8, and tumor necrosis factor-α in the spleen did not change significantly during this period, whereas the level of suppressor of cytokine signaling (SOCS)3 was significantly higher on 26 August than that on 16 July (p < 0.05). These results suggest that phagocytic activity of trunk kidney leukocytes and serum bactericidal activity against F. psychrophilum decreased with sexual maturation, and that SOCS3 may be related to the decrease in non-specific immune activity in ayu

Results from the Japan 2016 report card on physical activity for children and youth

Background: The Report Card on Physical Activity for Children and Youth aims to consolidate existing evidence, encourage more evidence-informed physical activity, and improve surveillance of physical activity. Methods: Application of Canada and Scotland Report Card methodology to Japan, adapted to Japanese circumstances and availability of data, and based on nationally representative surveys. Results: The 2016 Japan Report Card on Physical Activity for Children and Youth consists of Health Behaviors and Outcomes (7 indicators); and Influences on Health Behaviors (4 indicators). Three Health Behaviors and Outcomes received C grades (Participation in Sport; Sedentary Behavior; Recreational Screen Time; Physical Fitness), while two indicators could not be graded (Overall Physical Activity, and Active Play). The indicators Active Transportation (B) and Weight Status were favorable (A). In the Influences domain, Family Influence and Community and the Built Environment were graded as D, while the School & Childcare Settings and the Government Strategies and Investments were favorable (B). Conclusions: The Japan report card illustrated some favorable health behaviors, health outcomes, and influences. There is a need for more evidence especially on overall physical activity, active play, and community and the built environment

RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis

INTRODUCTION: We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40. METHODS: Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses. RESULTS: Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells. CONCLUSIONS: These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity

Inhibition of EP4 Signaling Attenuates Aortic Aneurysm Formation

BACKGROUND: Aortic aneurysm is a common but life-threatening disease among the elderly, for which no effective medical therapy is currently available. Activation of prostaglandin E(2) (PGE(2)) is known to increase the expression of matrix metalloproteinase (MMP) and the release of inflammatory cytokines, and may thus exacerbate abdominal aortic aneurysm (AAA) formation. We hypothesized that selective blocking of PGE(2), in particular, EP4 prostanoid receptor signaling, would attenuate the development of AAA. METHODS AND FINDINGS: Immunohistochemical analysis of human AAA tissues demonstrated that EP4 expression was greater in AAA areas than that in non-diseased areas. Interestingly, EP4 expression was proportional to the degree of elastic fiber degradation. In cultured human aortic smooth muscle cells (ASMCs), PGE(2) stimulation increased EP4 protein expression (1.4 ± 0.08-fold), and EP4 stimulation with ONO-AE1-329 increased MMP-2 activity and interleukin-6 (IL-6) production (1.4 ± 0.03- and 1.7 ± 0.14-fold, respectively, P<0.05). Accordingly, we examined the effect of EP4 inhibition in an ApoE(-/-) mouse model of AAA infused with angiotensin II. Oral administration of ONO-AE3-208 (0.01-0.5 mg/kg/day), an EP4 antagonist, for 4 weeks significantly decreased the formation of AAA (45-87% reduction, P<0.05). Similarly, EP4(+/-)/ApoE(-/-) mice exhibited significantly less AAA formation than EP4(+/+)/ApoE(-/-) mice (76% reduction, P<0.01). AAA formation induced by periaortic CaCl(2) application was also reduced in EP4(+/-) mice compared with wild-type mice (73% reduction, P<0.001). Furthermore, in human AAA tissue organ cultures containing SMCs and macrophages, doses of the EP4 antagonist at 10-100 nM decreased MMP-2 activation and IL-6 production (0.6 ± 0.06- and 0.7 ± 0.06-fold, respectively, P<0.05) without increasing MMP-9 activity or MCP-1 secretion. Thus, either pharmacological or genetic EP4 inhibition attenuated AAA formation in multiple mouse and human models by lowering MMP activity and cytokine release. CONCLUSION: An EP4 antagonist that prevents the activation of MMP and thereby inhibits the degradation of aortic elastic fiber may serve as a new strategy for medical treatment of AAA

Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis

<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that immune modulation can be accomplished by administration of gene silenced dendritic cells (DC) using siRNA. In this study, we demonstrate the therapeutic utilization of shRNA-modified DC as an antigen-specific tolerogenic vaccine strategy for autoimmune arthritis.</p> <p>Methods</p> <p>A shRNA that specifically targets IL-12 p35 was designed and cloned into a plasmid vectors (IL-12 shRNA). Bone marrow-derived DC from DBA/1 mice were transfected with the IL-12 shRNA construct in vitro. Mice with collagen II (CII)-induced arthritis (CIA) were treated with the modified DCs expressing the shRNA. Recall response and disease progression were assessed.</p> <p>Results</p> <p>After gene silencing of IL-12 in DC, DC were shown to selectively inhibit T cell proliferation on recall responses and in an MLR. In murine CIA, we demonstrated that administration of IL-12 shRNA-expressing DC that were pulsed with CII inhibited progression of arthritis. The therapeutic effects were evidenced by decreased clinical scores, inhibition of inflammatory cell infiltration in the joint, and suppression of T cell and B cell responses to CII.</p> <p>Conclusion</p> <p>We demonstrate a novel tolerance-inducing protocol for the treatment of autoimmune inflammatory joint disease in which the target antigen is known, utilizing DNA-directed RNA interference.</p

Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine

Conventional treatments for autoimmune diseases have relied heavily on nonspecific immune suppressants, which possess a variety of adverse effects without inhibiting the autoimmune process in a specific manner. In the present study we demonstrate the effectiveness of antigen-specific, maturation-resistant, tolerogenic dendritic cells (DC) in suppressing collagen-induced arthritis, a murine model of rheumatoid arthritis. Treatment of DC progenitors with the NF-κB inhibiting agent LF 15-0195 (LF) resulted in a population of tolerogenic DC that are characterized by low expression of MHC class II, CD40, and CD86 molecules, as well as by poor allostimulatory capacity in a mixed leukocyte reaction. Administering LF-treated DC pulsed with keyhole limpet hemocyanin antigen to naïve mice resulted hyporesponsiveness specific for this antigen. Furthermore, administration of LF-treated DC to mice with collagen-induced arthritis resulted in an improved clinical score, in an inhibited antigen-specific T-cell response, and in reduced antibody response to the collagen. The efficacy of LF-treated DC in preventing arthritis was substantiated by histological examination, which revealed a significant decrease in inflammatory cell infiltration in the joints. In conclusion, we demonstrate that in vitro-generated antigen-specific immature DC may have important potential as a tolerogenic vaccine for the treatment of autoimmune arthritis

Compliance with a physical activity guideline among junior high school students

Background: There were no nationwide moderate- to vigorous-intensity physical activity (MVPA) data relating to Japanese adolescents. This study assessed compliance with an MVPA guideline by adolescents, using a random sampling survey in Japan. The factors associated with compliance with the guideline were also examined. Methods: Participants were first- to third-grade Japanese junior high school students (307 boys and 255 girls). We analyzed data from the National Sports-Life Survey of Teens 2019, which used the Japanese version of physical activity (PA) questions in the World Health Organization Health Behavior in School-aged Children survey and potential correlates of MVPA. Results: Compliance with the PA guideline by the World Health Organization for Japanese students was 19.0% (95% confidence interval (CI), 15.8–22.3). The compliance of boys was significantly higher than that of girls (23.1%; 95% CI, 18.4–27.8; vs 14.1%; 95% CI, 9.8−18.4). The odds of meeting the PA guideline were significantly higher for boys in the second grade than boys in the first grade (odds ratio (OR) 1.78; 95% CI, 1.02–3.09), liking PA (for all: OR: 2.97; 95% CI, 1.32–6.69; for girls: OR: 2.99; 95% CI, 1.01–8.81), and sports participation (for all: OR: 4.77; 95% CI, 2.32–9.80; for boys: OR: 6.00; 95% CI, 1.81–19.89; for girls: OR: 4.08; 95% CI, 1.63–10.21). Conclusions: The results suggest that more than 80% of junior high school students were insufficiently physically active in Japan. Preferences for PA and sports participation may be important correlates of sufficient PA

Production of 9Be through alpha-fusion reaction of metal-poor cosmic ray and stellar flare

Spectroscopic observations of metal-poor stars have indicated possible 6Li abundances that are much larger than the primordial abundance predicted in the standard big bang nucleosynthesis model. Possible mechanisms of 6Li production in metal-poor stars include pregalactic and cosmological cosmic ray (CR) nucleosynthesis and nucleosynthesis by flare-accelerated nuclides. We study 9Be production via two-step alpha-fusion reactions of CR or flare-accelerated 3,4He through 6He and 6,7Li, in pregalactic structure, intergalactic medium, and stellar surfaces. We solve transfer equations of CR or flare particles and calculate nuclear yields of 6He, 6,7Li, and 9Be taking account of probabilities of processing 6He and 6,7Li into 9Be via fusions with alpha particles. Yield ratios, i.e., 9Be/6Li, are then calculated for the CR and flare nucleosynthesis models. We suggest that the future observations of 9Be in metal-poor stars may find enhanced abundances originating from metal-poor CR or flare activities.Comment: 28 pages, 9 figures, argument and new Fig. 5 added in section 4, minor modifications added, results slightly changed only quantitatively, minor modifications added agai