An intracellular self protein synthesized in macrophages is presented but fails to induce tolerance

Mice deficient for the fifth component of murine complement (C5), unlike normal mice, do not possess the secreted form of C5 in their body fluids and can be readily immunized to serum-derived normal C5. Although macrophages from C5-deficient mice do not secrete C5, they synthesize the precursor form (pro-C5). Therefore contact of T cells with autologous pro-C5 presented by macrophages is theoretically possible. We show that macrophages from C5-deficient mice can Indeed stimulate a class II restricted CS-specific T cell clone without addttion of exogenous C5. lmmunization of C5-deficient mice with autologous pro-C5 induces vigorous C5-specific T cell proliferation and pro-C5 is recognized by C5-specific T cells in vitro, demonstrating that this protein fails to induce tolerance under physiological condltions. Thus, intraceliuiar pro-C5 is processed and presented by C5-deficient macrophages and can activate T cell clones in vitro, yet is neither immunogenic nor tolerogenic for T cells in viv

Integration of corporate social responsibility into new product development

This study investigated seven core subjects of ISO 26000 to explore the way in which new product development (NPD) links corporate social responsibility (CSR) strategy with product development planning. This study thoroughly discussed the implementation of policies that achieve social responsibility within the context of NPD planning. Rapid changes in science and technology mean customer needs are changing faster than ever before, making it increasingly difficult to identify critical customer needs in a timely manner. NPD therefore is essential to enhance enterprise competitiveness. The construction of a CSR-based NPD model can help enterprises in NPD. Using the CSR based NPD model to plan materials selection, specification setting, manufacturing procedures and methods, distribution, servicing and recycling increases enterprise friendliness and happiness, and benefits their sustainable development. The findings of this study suggest that traditional enterprise activities focus on profit maximization and cost minimization. The profit-oriented strategy influences product design, purchase, production, manufacture and delivery. Poor working environment, overtime, low wages, neglect of health and safety, and various deficiencies in CSR frequently occur. If a CSR based perspective is initially adopted to implement public expectations regarding product design, it can be both beneficial and environmentally friendly

Autonomic Dysfunction Because of Severe Tetanus in an Unvaccinated Child

Tetanus is rare in a country with a national vaccination program. When it does occur, the associated autonomic dysfunction is a challenge for physicians. We report here a case of an unvaccinated 5-year-old boy who suffered from tetanus complicated by autonomic dysfunction, which was successfully controlled by the infusion of magnesium sulfate. This is the first case that demonstrated the therapeutic effect of magnesium sulfate in a child with tetanus. This case highlights the importance of implementing a vaccination program

Immuno-modulatory activity of Ganoderma lucidum-derived polysacharide on human monocytoid dendritic cells pulsed with Der p 1 allergen

<p>Abstract</p> <p>Background</p> <p><it>Ganoderma lucidum</it>-derived polysaccharide (PS-G) can rapidly and effectively promote the activation and maturation of immature dendritic cells (DCs), suggesting that PS-G possesses the capacity to regulate immune responses. This study aimed to clarify the immunologic effect of PS-G on monocyte-derived dendritic cells (MD-DCs) from asthmatic children allergic to house dust mites. The MD-DCs were stimulated for 24 h with the related allergen, Der p 1, in the presence or absence of PS-G. Cell surface markers and phagocytic capacity were assessed by FACS analysis, and key polarizing cytokines (IL-12 p40, IL-12 p70, IL-6, IL-23, and IL-10) were quantified. The subsequent regulatory effect of pulsed MD-DCs on naïve T cells was evaluated by determining the T-cell cytokine profile.</p> <p>Results</p> <p>PS-G induced the maturation of MD-DCs and decreased phagocytic capacity, even if pulsed with Der p 1. After incubation with PS-G and Der p 1, MD-DCs produced higher amounts of IL-12 p70, IL-12 p40, IL-6, IL-23, and IL10 than Der p 1-pulsed DCs. Furthermore, type 1 helper T (Th1) cell cytokine (INF-γ) production was highly increased when naïve autologous T cells were co-cultured with Der p 1-pulsed MD-DCs. Naïve T cells stimulated by MD-DCs pulsed with Der p 1 failed to produce proliferation of T-cells, whereas the addition of PS-G to Der p 1 induced a significant proliferation of T-cells similar to that observed with PS-G alone.</p> <p>Conclusion</p> <p>The presence of PS-G in an allergen pulse promoted allergic MD-DCs to produce IL-12 p70, IL-12 p40, IL-6, IL-23, and IL-10, and exerted an effect on shifting the immune balance towards Th1 in children with allergic asthma.</p

Comparison of Renal Function and Other Health Outcomes in Vegetarians versus Omnivores in Taiwan

Renal disease is one of the top 10 leading causes of death, and the incidence of end-stage renal disease in Taiwan is the highest in the world. Many dietitians consider the diet of plant origin consumed by vegans to be ‘lighter’ and ‘more healthful’ than the diet of both plant and animal origin consumed by omnivores. Dietary protein has significant effects on renal functions. The study explored the effects of both the diets on renal functions. The study subjects included 102 Buddhist nun vegetarians and an equal number of matched control group (omnivores). A cross-sectional study was performed to investigate the effects of the diet of plant origin and the diet of both plant and animal origin on renal functions. There was no difference in the renal functions between the two groups. However, systolic blood pressure, blood urea nitrogen, serum sodium, glucose, cholesterol levels, and urinary specific gravity were lower in the vegetarian group. Although these results were compatible with general concepts regarding diet of plant origin, after adjusting for age, the duration of intake of this diet had no effect on the renal functions. Based on the findings, it is concluded that the renal functions, in terms of the estimated glomerular filtration rate, were not different between the vegetarians and the omnivores

Dual Supramolecular Nanoparticle Vectors Enable CRISPR/Cas9-Mediated Knockin of Retinoschisin 1 Gene-A Potential Nonviral Therapeutic Solution for X-Linked Juvenile Retinoschisis.

The homology-independent targeted integration (HITI) strategy enables effective CRISPR/Cas9-mediated knockin of therapeutic genes in nondividing cells in vivo, promising general therapeutic solutions for treating genetic diseases like X-linked juvenile retinoschisis. Herein, supramolecular nanoparticle (SMNP) vectors are used for codelivery of two DNA plasmids-CRISPR-Cas9 genome-editing system and a therapeutic gene, Retinoschisin 1 (RS1)-enabling clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) knockin of the RS1 gene with HITI. Through small-scale combinatorial screenings, two SMNP vectors, with Cas9 and single guide RNA (sgRNA)-plasmid in one and Donor-RS1 and green fluorescent protein (GFP)-plasmid in the other, with optimal delivery performances are identified. These SMNP vectors are then employed for CRISPR/Cas9 knockin of RS1/GFP genes into the mouse Rosa26 safe-harbor site in vitro and in vivo. The in vivo study involves intravitreally injecting the two SMNP vectors into the mouse eyes, followed by repeated ocular imaging by fundus camera and optical coherence tomography, and pathological and molecular analyses of the harvested retina tissues. Mice ocular organs retain their anatomical integrity, a single-copy 3.0-kb RS1/GFP gene is precisely integrated into the Rosa26 site in the retinas, and the integrated RS1/GFP gene is expressed in the retinas, demonstrating CRISPR/Cas9 knockin of RS1/GFP gene

Adipose extracellular matrix remodelling in obesity and insulin resistance

The extracellular matrix (ECM) of adipose tissues undergoes constant remodelling to allow adipocytes and their precursor cells to change cell shape and function in adaptation to nutritional cues. Abnormal accumulation of ECM components and their modifiers in adipose tissues has been recently demonstrated to cause obesity-associated insulin resistance, a hallmark of type 2 diabetes. Integrins and other ECM receptors (e.g. CD44) that are expressed in adipose tissues have been shown to regulate insulin sensitivity. It is well understood that a hypoxic response is observed in adipose tissue expansion during obesity progression and that hypoxic response accelerates fibrosis and inflammation in white adipose tissues. The expansion of adipose tissues should require angiogenesis; however, the excess deposition of ECM limits the angiogenic response of white adipose tissues in obesity. While recent studies have focused on the metabolic consequences and the mechanisms of adipose tissue expansion and remodelling, little attention has been paid to the role played by the interaction between peri-adipocyte ECM and their cognate cell surface receptors. This review will address what is currently known about the roles played by adipose ECM, their modifiers, and ECM receptors in obesity and insulin resistance. Understanding how excess ECM deposition in the adipose tissue deteriorates insulin sensitivity would provide us hints to develop a new therapeutic strategy for the treatment of insulin resistance and type 2 diabetes