UNASSIGNED: Ginsenosides are biologically active components of ginseng and have various functions. In this study, we investigated the immunomodulatory activity of a ginseng product generated from ginseng powder (GP) via enzymatic bioconversion. This product, General Bio compound K-10 mg solution (GBCK10S), exhibited increased levels of minor ginsenosides, including ginsenoside-F1, compound K, and compound Y.
UNASSIGNED: The immunomodulatory properties of GBCK10S were confirmed using mice and a human natural killer (NK) cell line. We monitored the expression of molecules involved in immune responses via enzyme-linked immunosorbent assay, flow cytometry, NK cell-targeted cell destruction, quantitative reverse-transcription real-time polymerase chain reaction, and Western blot analyses.
UNASSIGNED: Oral administration of GBCK10S significantly increased serum immunoglobulin M levels and primed splenocytes to express pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ. Oral administration of GBCK10S also activated NK cells in mice. Furthermore, GBCK10S treatment stimulated a human NK cell line in vitro, thereby increasing granzyme B gene expression and activating STAT5.
UNASSIGNED: GBCK10S may have potent immunostimulatory properties and can activate immune responses mediated by B cells, Th1-type T cells, and NK cells.

Matrix metalloproteinase (MMP)-2 and MMP-9, also known as gelatinases or type IV collagenases, are recognized as major contributors to the proteolytic degradation of extracellular matrix during tumor invasion. Latent MMP-2 (proMMP-2) is activated by membrane type 1 MMP (MT1-MMP) on the cell surface of tumor cells. We previously reported that cell-bound proMMP-9 is activated by the MT1-MMP/MMP-2 axis in HT1080 cells treated with concanavalin A in the presence of exogenous proMMP-2. However, the regulatory mechanism of proMMP-9 activation remains largely unknown. Transforming growth factor (TGF)-β1 is frequently overexpressed in tumor tissues and is associated with tumor aggressiveness and poor prognosis. In this study, we examined the role of TGF-β1 on MT1-MMP-mediated proMMP-9 activation using human oral squamous cell carcinoma cells. TGF-β1 significantly increased the expression of MMP-9. By adding exogenous proMMP-2, TGF-β1-induced proMMP-9 was activated during collagen gel culture, which was suppressed by the inhibition of TGF-β1 signaling or MT1-MMP activity. This MT1-MMP-mediated proMMP-9 activation was needed to facilitate TGF-β1-induced cell invasion into collagen gel. Thus, TGF-β1 may facilitate MT1-MMP-mediated MMP-9 activation and thereby stimulate invasion of tumor cells in collaboration with MT1-MMP and MMP-2.

N-glycosylation is a physiologically vital post-translational modification of proteins in eukaryotic organisms. Initial work on Haemonchus contortus - a blood-sucking nematode of ruminants with a broad geographical distribution - has shown that this parasite harbors N-glycans with exclusive chitobiose modifications. Besides, several immunogenic proteins (e.g., amino- and metallo-peptidases) are known to be N-glycosylated in adult worms. However, an informative atlas of N-glycosylation in H. contortus is not yet available. Herein, we report 291 N-glycosylated proteins with a total of 425 modification sites in the parasite. Among them, many peptidase families (e.g., peptidase C1 and M1) including potential vaccine targets were enriched. Notably, the glycan-rich conjugates are distributed primarily in the intestine and gonads of adult worms, and consequently hidden from the host\'s immune system. Collectively, these data provide a comprehensive atlas of N-glycosylation in a prevalent parasitic nematode while underlining its significance for infection, immunity and prevention.

Certain food components possess immunomodulatory effects. The aim of this study was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa L. We demonstrated an enhancement of natural killer (NK) activity and interferon (IFN)-γ production in mice that were orally administered an insoluble fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced IFN-γ production in mouse spleen cells in an interleukin (IL)-12-dependent manner, and NK1.1+ cells were the main cells responsible for producing IFN-γ. Additionally, the results suggested that the active compounds in the insoluble fraction were recognized by Toll-like receptor (TLR) 2, TLR4, and C-type lectin receptors on dendritic cells, and they activated signaling cascades such as MAPK, NF-κB, and Syk. These findings suggest that B. rapa L. is a potentially promising immuno-improving material, and it might be useful for preventing immunological disorders such as infections and cancers by activating innate immunity.

G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs). The short-splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T-lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure in Git2 (-/-) mice. CD4(+) T cells from Git2 (-/-) mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR-stimulated activation. Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

A novel pure-oxygen pressurized biofilm reactor was operated at different organic loading, mechanical shear and hydrodynamic conditions to understand the relationships between biofilm architecture and its operation. The ultimate goal was to improve the performance of the biofilm reactor. The biofilm was labeled with seven stains and observed with confocal laser scanning microscopy. Unusual biofilm architecture of a ribbon embedded between two surfaces with very few points of attachment was observed. As organic loading increased, the biofilm morphology changed from a moderately rough layer into a locally smoother biomass with significant bulging protuberances, although the chemical oxygen demand (COD) removal efficiency remained unchanged at about 75%. At higher organic loadings, biofilms contained a larger fraction of active cells distributed uniformly within a proteinaceous matrix with decreasing polysaccharide content. Higher hydrodynamic shear in combination with high organic loading resulted in the collapse of biofilm structure and a substantial decrease in reactor performance (a COD removal of 16%). Moreover, the important role of proteins for the spatial distribution of active cells was demonstrated quantitatively.

The immunomodulatory effects of live or non-viable lactic acid bacteria have been extensively investigated. We reported that oral intake of heat-killed Lactobacillus plantarum L-137 (HK L-137) augmented innate and acquired immunity in mice and human subjects. To examine the effects of HK L-137 intake on upper respiratory tract infection (URTI) symptoms and immune functions in human subjects, a randomised, double-blind, placebo-controlled, parallel study was conducted in subjects with high psychological stress levels. A total of seventy-eight healthy subjects (thirty-three men and forty-five women; mean age 50·6 years) with scores of >41 on eighteen-item subscales of psychological distress in the Brief Job Stress Questionnaire were randomly assigned to receive a tablet containing HK L-137 (10 mg) or a placebo tablet daily for 12 weeks. The URTI symptoms were rated once daily on the validated twenty-one-item Wisconsin Upper Respiratory Symptom Survey-21. Immune functions, such as concanavalin A-induced proliferation and percentages of interferon (IFN)-γ- and IL-4-producing CD4 T cells of peripheral blood mononuclear cells (PBMC), and serum IFN-β concentrations were measured every 4 weeks. URTI incidence was significantly lower in the HK L-137 group than in the control group. URTI incidence, duration and severity, and duration of medication showed significant negative correlations with duration of HK L-137 intake. The percentage change from baseline of concanavalin A-induced proliferation of PBMC was significantly greater in the HK L-137 group than in the control group. These findings suggest that daily HK L-137 intake can decrease URTI incidence in healthy subjects, possibly through augmentation of immune functions.