• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.6
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• pp.683-689
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• 2006

This study was established to investigate the effect of germanium-fortified yeasts on the serum lipid composition and immune system of human body. All 50 subjects with the age range of $50{\sim}75$ were entered in this clinical trial for 6 months. The effects were determined by the proliferative responses of immune-mediated cells, T-cell, B-cell and NK-cell during daily supplementation with/without germanium-fortified yeast. The results of hematology and blood chemistry didn't show any significant differences during administration periods. Serum lipid compositions also didn't show any significant differences during administration periods except triglyceride (TG) and VLDL-cholesterol. TG and VLDL-cholesterol levels were increased significantly by the consumption of germanium-fortified yeast (p<0.05). Immune mediated T-celt and NK-cell didn't increased in both control and test group supplemented with germanium fortified yeast, while B-cell increased in the germanium fortified yeast group after 8 week (p<0.05). Also $TNF-{\alpha}$ increased in the group of germanium fortified yeast after 8 week (p<0.05) but not in the control group. From the above results, germanium fortified yeast is expected to be useful on the improvement of the cellular immune response and protection of organs from various chronic diseases.

• Molecules and Cells
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• v.45 no.12
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

• Parasites, Hosts and Diseases
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• v.29 no.3
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• pp.279-292
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• 1991

The immune response to sheep red blood cell (sRBC) was monitored in the mice infected with Ascaris strum or Trichinella spiralis. The effects of the infection with T. spiralis or the injection with cyclophosphamide (CY) as an immunosuppression agent prior to challenge infection with the embryonated eggs of A. suum were monitored in mice by means of the level of infection with A. strum and cellular and humoral immune response to sRBC. following the oral administration of 1, 000 eggs of A. suum to mice, delayed-type hypersensitivity (DTH) and rosette-forming rate were gradually decreased and reached to the lowest levels at the 5th week and 6th week postinfection, respectively, and then returned to normal at the loth week. The hemagglutinin (HA) and hemolysin (HE) titers were gradually elevated and reached to peak at the 3rd week postinfection, and then returned to normal level. The appearance ratios of the eosinophils and mast cells were in peak at the 4th week and the 2nd week postinfection, respectively. Meanwhile the harvest ratio of A. suum larvae from the liver and lungs was 21.97% at the 1st week postinfection. Following the oral administration of 300 T. spiralis infective larvae, DTH and rosette-forming rate were gradually decreased with the lapse of time and reached the lowest values in the 30th and 21st day of postinfection, and then slightly increased and transiently decreased in the 70th and 80th day of postinfection, respectively. HA and HE titers were the lowest in the 21st and 90th day, whereas the ratios of eosinophils and mast cells were the highest on the 40th and 14th day posti nfecti on, ruts petit i vela. Following the intraperitoneal injection of CY, the body weight, the spleen weight, DTH, rosette-orming ratio, HA and HE titers, the number of WBC and the ratio of the mast cell were predominantly decreased in the 5th day, and then returned to the same value of the 1st day postinjection. The ratio of eosinophils was gradually decreased following to advance of days. At the 1st, 5th and loth days after intraperitoneal injection of CY of 400 mg/kg, a dose with 1, 000 eggs of A. suum was administered orally to mice, and harvest rate of the larvae at the 7th day postadministration was 7.07% in the 1st day, 14.94% in the 5th day, 10.1% in the loth day, 8.02% in control group. The effect of prior infection with infective larvae of T. spiralis upon immunological sequelae of a challenge infection of mice with embryonated eggs of A. suum in 30 or 70 days interval was checked. On the 37th day of prior infection with T. spiralis, that was the 7th day with A. suum postinfection, DTH and rosette-forming rate were drastically decreased, but the ratio of mast cells was highly increased and the ratio of eosinophils, HA and HE titers were fairly increased. On the other hand, the rate of larvae harvest was 9.3% in experimental group in contrast with 22.18% in control group. Meanwhile the effect of immune response to sRBC was similar to that of the former, but DTH and rosettt-forming rate were greatly decreased in the 77th day after prior infection with the 7th day after challenge infection in compariton with control. At that time, Ascaris larvae were harvested 8.3% in experimental group in comparison with 10.5% in control group.

• Biomedical Science Letters
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• v.19 no.2
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• pp.118-123
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• 2013

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a proinflammatory cytokine that mediates the inflammatory response and immune functions, and modulates the proliferation, differentiation and cell death of cancer cells. The differential functions of TNF-${\alpha}$ in various human cells due to the formation of different stimulating pathway upon the binding of TNF-${\alpha}$ to its receptors. In the present study, we examined the different effects of TNF-${\alpha}$ on the survival and apoptosis between normal granulocytes and human myeloid leukemia HL-60 cells. Although TNF-${\alpha}$ did not affect on the constitutive apoptosis of granulocytes, TNF-${\alpha}$ strongly induced the apoptosis of HL-60 cells in a dose- and a time-dependent manner. TNF-${\alpha}$-induced apoptosis was occurred via the activation of caspase 8, caspase 9 and caspase 3/7 and the induction of ROS production in HL-60 cells. Also, BAY-11-7085, a NF-${\kappa}B$ inhibitor, blocked the TNF-${\alpha}$-induced apoptosis in HL-60 cells. NF-${\kappa}B$ may be involved in TNF-${\alpha}$-induced apoptotic signaling pathway in HL-60 cells. These results suggest that TNF-${\alpha}$ activates apoptotic pathways and its process depends on cell type and many cellular factors. A better understanding of the differential effect of TNF-${\alpha}$ on cell apoptosis and survival may provide important information that can be used to elucidate the specific inhibitory effect of TNF-${\alpha}$ on the cancer dis.

• IMMUNE NETWORK
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• v.2 no.3
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• pp.133-136
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• 2002

Background: The costimulatory molecule 4-1BB, a member of nerve growth factor receptor/tumor necrosis factor (NGFR/TNFR) super family, is involved in cell survival and death. Methods: In this study, female C57BL/6 ($H-2^b$) mice were used as a recipient, and DBA/2 ($H-2^d$) as a donor to assess a mixed lymphocyte reaction (MLR) and CTL response in vitro, and skin graft survival. IL-2, IFN level was measured by ELISA. Results: Mixed lymphocyte reaction (MLR) analysis showed that 4-1BB-deficient responder cells showed enhanced cellular proliferation over littermate controls. In contrast, IL-2 production was diminished only in 4-1BB knockout cultures. The IFN expression, on the other hand, was comparable between the groups. When female C57BL/6 ($H-2^b$) mice were grafted with the trunk skin of DBA/2 ($H-2^d$) mice, the in vivo tissue destruction of 4-1BB-deficient mice was not distinct from the normal littermates. Conclusion: These data suggest that 4-1BB is critical for the induction of alloreactive responses in vitro but 4-1BB alone could not change the course of skin rejection in vivo.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.136-144
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• 2018

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Bacillus Calmette-$Gu\acute{e}rin$ (BCG) vaccine is the only TB vaccine currently available, but it is not sufficiently effective in preventing active pulmonary TB or adult infection. With the purpose of developing an improved vaccine against TB that can overcome the limitations of the current BCG vaccine, we investigated whether adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS) are capable of enhancing the immunogenicity and protective efficacy of TB subunit vaccines. The results revealed that the dLOS/dimethyl dioctadecyl ammonium bromide (DDA) adjuvant formulation significantly increased both humoral and Th1-type cellular responses to TB subunit vaccine that are composed of three antigens, Ag85A, ESAT-6, and HspX. The adjuvanted TB vaccine also effectively induced the Th1-type response in a BCG-primed mouse model, suggesting a potential as a booster vaccine. Finally, the dLOS/DDA-adjuvanted TB vaccine showed protective efficacy against M. tuberculosis infection in vitro and in vivo. These data indicate that the dLOS/DDA adjuvant enhances the Th1-type immunity and protective efficacy of the TB subunit vaccine, suggesting that it would be a promising adjuvant candidate for the development of a booster vaccine.

• IMMUNE NETWORK
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• v.13 no.5
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• pp.213-217
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• 2013

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

• Journal of Periodontal and Implant Science
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• v.30 no.3
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• pp.675-687
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• 2000

Multiple periodontal pathogens sequentially colonize the subgingival niche during the conversion from gingivitis to destructive periodontal disease. An animal model of sequential immunization with key periodontal pathogens has been developed to determine whether T and B lymppocyte effector functions are skewed and fail to protect the host from pathogenic challenge. The present study was performed to evaluate immunomodulatory effect of exposure to Fusobacterium nucleatum(F. nucleatum) prior to Porphyromonas gingivalis(P. gingi - valis). Group 1(control) mice were immunized with phosphate-buffered saline, Group 2 were immunized with F. nucleatum prior to P. gingivalis, while Group 3 were immunized P. gingivalis alone. All the T cell clones derived from Group 2 demonstrated type 2 helper T cell clone(Th2 subsets), while those from Group 3 mice demonstrated Th1 subsets. Exposure of mice to F . nucleatum prior to P. gingivalis interfered with opsonophagocytosis function of sera against P. gingivalis. In adoptive T cell transfer experiments, in vivo protective capacity type 2 helper T cell clones(Th2) from Group 2 was significantly lower than type 1 helper T cell clones(Th1) from Group 3 against the lethal dose infection of P. gingivalis. Western blot analysis indicated the different pattern of recognition of P .gingivalis fimbrial proteins between sera from Group 2 and Group 3. In conclusion, these study suggest that colonization of the subgingival niche by F .nucleatum prior to the periodontal pathogen, P. gingivalis, modulates the host immune responses to P. gingivalis at humoral, cellular and molecular levels.

• Journal of Oriental Neuropsychiatry
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• v.19 no.3
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• pp.55-68
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• 2008

Background: Microglia produces a barrage of factors (IL-l, TNF-$\alpha$, NO, superoxide) that are toxic to neurons and playa major role in the cellular immune response associated with the pathology of Alzheimer's disease(AD). OJaJiHwangEumJa(OJJHEJ) has been usually used for the treatment of senile disorders. For enhancing efficacy and convenience, the change of the drug delivery device of oriental herbal medicine is required. Objective: This experiment was designed to investigate the effect of the OJJHEJ hot water extract & ultra-fine powder on proinflammatory cytokine of microglia and memory deficit model. Method: The effects of the OJJHEJ hot water extract on production of IL-1$\beta$, IL-6, TNF-$\alpha$, in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. The effects of the OJJHEJ hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine and AChE in serum of the memory deficit mice induced by scopolamine were investigated. Results: 1. The OJJHEJ hot water extract suppressed the production of IL-1$\beta$, IL-6, TNF-$\alpha$ in BV2 microglial cell line and the production of IL-6 was suppressed significantly. 2. The OJJHEJ hot water extract & ultra-fine powder decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 3. The OJJHEJ hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. Conclusions: This experiment shows that the OJJHEJ hot water extract & ultra-fine powder might be effective for the prevention and treatment of memory impairment diseases. Investigation into the clinical use of the OJJHEJ hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4217-4224
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• 2014

Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA remain elusive. The present study was designed to investigate whether peripheral blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We indentified informative PBLs gene expression profiles that could reliably distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117 genes were up regulated and 60 were down regulated. The molecular and cellular functions predicted for these CCA specific genes according to the Gene Ontology database indicated differential PBL expression of host immune response and tumor progression genes (EREG, TGF ${\beta}1$, CXCL2, CXCL3, IL-8, and VEGFA). The expression levels of 9 differentially expressed genes were verified in 36 CCA vs 20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and SERPINB2) computed as "prognostic index" was found to be an independent and statistically significant predictor for CCA patient survival. The present study shows that CCA PBLs may serve as disease predictive clinically accessible surrogates for indentifying expressed genes reflective of CCA disease severity.