Orthogonal test design for optimization of the extraction of polysaccharides from Phascolosoma esulenta and evaluation of its immunity activity

Yield of polysaccharides from Phascolosoma esulenta obtained by phosphate buffer extraction through an orthogonal experiment (L₉(3)⁴) were investigated to get the best extraction conditions. The results showed that extraction temperature, ratio of phosphate buffer to raw material, extraction time, and ratio of trypsinase to raw material were the main four variables that influenced the yields of extracts. The highest yield was obtained when extraction temperature, ratio of phosphate buffer to raw material, extraction time and ratio of trypsinase to raw material were 40 °C, 2, 5.5 h and 1.6, respectively. The immunity-stimulating method showed that polysaccharides from P. esulenta could significantly raise liver, spleen and thymus index of mice and enhance Con A-stimulated mouse spleen cells proliferation. These results indicate that polysaccharides from P. esulenta had significantly higher immunity-stimulating activities.     

The Design and Characterization of Receptor-selective APRIL Variants

A proliferation-inducing ligand (APRIL), a member of the TNF ligand superfamily with an important role in humoral immunity, is also implicated in several cancers as a prosurvival factor. APRIL binds two different TNF receptors, B cell maturation antigen (BCMA) and transmembrane activator and cylclophilin ligand interactor (TACI), and also interacts independently with heparan sulfate proteoglycans. Because APRIL shares binding of the TNF receptors with B cell activation factor, separating the precise signaling pathways activated by either ligand in a given context has proven quite difficult. In this study, we have used the protein design algorithm FoldX to successfully generate a BCMA-specific variant of APRIL, APRIL-R206E, and two TACI-selective variants, D132F and D132Y. These APRIL variants show selective activity toward their receptors in several in vitro assays. Moreover, we have used these ligands to show that BCMA and TACI have a distinct role in APRIL-induced B cell stimulation. We conclude that these ligands are useful tools for studying APRIL biology in the context of individual receptor activation.     

Granuloma formation to Capillaria hepatica eggs. I. Descriptive definition

The course of the cellular response in the liver to nonembryonated Capillaria hepatica (Bancroft, 1893) eggs given by intravenous injection into the portal circulation of unsensitized and sensitized mice was studied qualitatively and quantitatively. A gradual infiltration of predominantly mononuclear cells occurred around the eggs in the liver, leading to the formation of distinct granulomatous lesions characterized by macrophages and lymphocytes. This was followed by an infiltration of eosinophils. Previous intraperitoneal sensitization led to an earlier and an enhanced reaction to an intravenous challenge with eggs. Specificity of the cellular response was suggested by the lack of an enhanced reaction to presensitization with eggs of a closely related species, Trichuris muris. These studies indicate that granuloma formation to C. hepatica eggs has an immunological basis and furthermore the cell composition of the granuloma would suggest that a cell-mediated component may be involved as part of the specific response.     

Activation of the Transcription Factor FosB/Activating Protein-1 (AP-1) Is a Prominent Downstream Signal of the Extracellular Nucleotide Receptor P2RX7 in Monocytic and Osteoblastic Cells

Activation of the ionotropic P2RX7 nucleotide receptor by extracellular ATP has been implicated in modulating inflammatory disease progression. Continuous exposure of P2RX7 to ligand can result in apoptosis in many cell types, including monocytic cells, whereas transient activation of P2RX7 is linked to inflammatory mediator production and the promotion of cell growth. Given the rapid hydrolysis of ATP in the circulation and interstitial space, transient activation of P2RX7 appears critically important for its action, yet its effects on gene expression are unclear. The present study demonstrates that short-term stimulation of human and mouse monocytic cells as well as mouse osteoblasts with P2RX7 agonists substantially induces the expression of several activating protein-1 (AP-1) members, particularly FosB. The potent activation of FosB after P2RX7 stimulation is especially noteworthy considering that little is known concerning the role of FosB in immunological regulation. Interestingly, the magnitude of FosB activation induced by P2RX7 stimulation appears greater than that observed with other known inducers of FosB expression. In addition, we have identified a previously unrecognized role for FosB in osteoblasts with respect to nucleotide-induced expression of cyclooxygenase-2 (COX-2), which is the rate-limiting enzyme in prostaglandin biosynthesis from arachidonic acid and is critical for osteoblastic differentiation and immune behavior. The present studies are the first to link P2RX7 action to FosB/AP-1 regulation in multiple cell types, including a role in nucleotide-induced COX-2 expression, and support a role for FosB in the control of immune and osteogenic function by P2RX7.     

How Metabolism Generates Signals during Innate Immunity and Inflammation

The interplay between immunity, inflammation, and metabolic changes is a growing field of research. Toll-like receptors and NOD-like receptors are families of innate immune receptors, and their role in the human immune response is well documented. Exciting new evidence is emerging with regard to their role in the regulation of metabolism and the activation of inflammatory pathways during the progression of metabolic disorders such as type 2 diabetes and atherosclerosis. The proinflammatory cytokine IL-1β appears to play a central role in these disorders. There is also evidence that metabolites such as NAD⁺ (acting via deacetylases such as SIRT1 and SIRT2) and succinate (which regulates hypoxia-inducible factor 1α) are signals that regulate innate immunity. In addition, the extracellular overproduction of metabolites such as uric acid and cholesterol crystals acts as a signal sensed by NLRP3, leading to the production of IL-1β. These observations cast new light on the role of metabolism during host defense and inflammation.     

Effect of adenovirus and influenza virus infection on obesity

The purpose of this review is to provide an overview of the effects of adenovirus and influenza virus infections on obesity in various experimental models. We reviewed studies that were conducted within the past 10 years and were related to virus infection and obesity prevalence. Here, we discuss a different causal relationship between adenovirus and influenza infections with obesity. Adenovirus infection can cause obesity, whereas obesity can be a risk factor for increasing influenza virus infection and increases the risk of morbidity and mortality. The prevalence of obesity due to adenovirus infections may be due to an increase in glucose uptake and reduction in lipolysis caused by an increase in corticosterone secretion. Adenovirus infections may lead to increases in appetite by decreasing norepinephrine and leptin levels and also cause immune dysfunction. The relationship between obesity and influenza virus infection could be summarized by the following features: decreases in memory T-cell functionality and interferon (IFN)-α, IFN-β, and IFN-γ mRNA expression, increases in viral titer and infiltration, and impaired dendritic cell function in obese individuals. Moreover, leptin resistance may play an important role in increasing influenza virus infections in obese individuals. In conclusion, prevention of adenovirus infections could be a good approach for reducing obesity prevalence, and prevention of obesity could reduce influenza virus infections from the point of view of viral infections and obesity.     

Associations between manganese exposure and multiple immunological parameters in manganese-exposed workers healthy cohort

BackgroundManganese (Mn) ions play a crucial role in the immune response. The immunotoxicity of Mn is rarely reported compared with the neurotoxicity of Mn.ObjectivesThe purpose of this study was to investigate the associations between chronic Mn exposure and immunological parameters in occupational Mn-exposed workers.MethodsA total of 538 workers were selected from the follow-up of manganese-exposed workers healthy cohort (MEWHC) in 2017. We divided the workers into the low-exposure group and the high-exposure group by the cutoff of the manganese-time weighted average (Mn-TWA) setting at 0.15 mg/m³. We examined serum immunological parameters by the immunoturbidimetric method and leukocyte counts and ratios in blood routine. Then we used the generalized linear model analyses and spline analyses to explore the associations between external exposure of Mn and multiple immunological parameters adjusted for variables. Based on the epidemiological analyses, we used Elisa (enzyme-linked immune sorbent assay) to detect plasma complement C3 of Mn-exposed rats.ResultsIn male workers, the mean value of complement C3 was 1.20 ± 0.16 g/L in the high-exposure group, which was significantly lower as compared to the low-exposure group (1.25 ± 0.18 g/L, P = 0.023). The generalize linear models’ analyses showed that complement C3 value had a significantly negative association with external exposure of Mn included adjustment for variables (β = -0.04, P = 0.035). Moreover, in male rats, the high-exposure group also had a lower level of complement C3 compared with the low-exposure group (P < 0.001). None significant association was observed in immunological parameters among female workers and rats (all P > 0.05).ConclusionsMn exposure from inhalable dust was associated with decreased complement C3 among occupationally Mn-exposed male individuals but not in female workers, which was further confirmed by the rat model. Further research into the possible mechanism of C3 reduction is needed in the future.