• Molecules and Cells
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• v.45 no.7
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• pp.502-511
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• 2022

Bacterial volatile compounds (BVCs) exert beneficial effects on plant protection both directly and indirectly. Although BVCs have been detected in vitro, their detection in situ remains challenging. The purpose of this study was to investigate the possibility of BVCs detection under in situ condition and estimate the potentials of in situ BVC to plants at below detection limit. We developed a method for detecting BVCs released by the soil bacteria Bacillus velezensis strain GB03 and Streptomyces griseus strain S4-7 in situ using solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). Additionally, we evaluated the BVC detection limit in the rhizosphere and induction of systemic immune response in tomato plants grown in the greenhouse. Two signature BVCs, 2-nonanone and caryolan-1-ol, of GB03 and S4-7 respectively were successfully detected using the soil-vial system. However, these BVCs could not be detected in the rhizosphere pretreated with strains GB03 and S4-7. The detection limit of 2-nonanone in the tomato rhizosphere was 1 µM. Unexpectedly, drench application of 2-nonanone at 10 nM concentration, which is below its detection limit, protected tomato seedlings against Pseudomonas syringae pv. tomato. Our finding highlights that BVCs, including 2-nonanone, released by a soil bacterium are functional even when present at a concentration below the detection limit of SPME-GC-MS.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.337-347
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• 2022

Coronavirus disease 2019 (COVID-19) is currently a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 are directly associated with hyper-activation of innate immune response that excessively produce pro-inflammatory cytokines and induce cytokine storm, leading to multi-organ-failure and significant morbidity/mortality. Currently, several antiviral drugs such as Paxlovid (nirmatrelvir and ritonavir) and molnupiravir are authorized to treat mild to moderate COVID-19, however, there are still no drugs that can specifically fight against challenges of SARS-CoV-2 variants. Panax ginseng, a medicinal plant widely used for treating various conditions, might be appropriate for this need due to its anti-inflammatory/cytokine/viral activities, fewer side effects, and cost efficiency. To review Panax ginseng and its pharmacologically active-ingredients as potential phytopharmaceuticals for treating cytokine storm of COVID-19, articles that reporting its positive effects on the cytokine production were searched from academic databases. Experimental/clinical evidences for the effectiveness of Panax ginseng and its active-ingredients in preventing or mitigating cytokine storm, especially for the cascade of cytokine storm, suggest that they might be beneficial as an adjunct treatment for cytokine storm of COVID-19. This review may provide a new approach to discover specific medications using Panax ginseng to control cytokine storm of COVID-19.

• Genomics & Informatics
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• v.21 no.2
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• pp.23.1-23.9
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• 2023

The mammalian sirtuin family, consisting of SIRT1-SIRT7, plays a vital role in various biological processes, including cancer, diabetes, neurodegeneration, cardiovascular disease, cellular metabolism, and cellular homeostasis maintenance. Due to their involvement in these biological processes, modulating sirtuin activity seems promising to impact immuneand aging-related diseases, as well as cancer pathways. However, more understanding is required regarding the safety and efficacy of sirtuin-targeted therapies due to the complex regulatory mechanisms that govern their activity, particularly in the context of multiple targets. In this study, the interaction landscape of the sirtuin family was analyzed using a systems biology approach. A sirtuin protein-protein interaction network was built using the Cytoscape platform and analyzed using the NetworkAnalyzer and stringApp plugins. The result revealed the sirtuin family's association with numerous proteins that play diverse roles, suggesting a complex interplay between sirtuins and other proteins. Based on network topological and functional analysis, SIRT1 was identified as the most prominent among sirtuin family members, demonstrating that 25 of its protein partners are involved in cancer, 22 in innate immune response, and 29 in aging, with some being linked to a combination of two or more pathways. This study lays the foundation for the development of novel therapies that can target sirtuins with precision and efficacy. By illustrating the various interactions among the proteins in the sirtuin family, we have revealed the multifaceted roles of SIRT1 and provided a framework for their possible roles to be precisely understood, manipulated, and translated into therapeutics in the future.

• Parasites, Hosts and Diseases
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• v.62 no.1
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• pp.30-41
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• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

• Molecules and Cells
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• v.41 no.4
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• pp.271-281
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• 2018

IFIT1 (also known as ISG56) is a member of the interferon-inducible protein with tetratricopeptide repeats (IFITs) family. IFITs are strongly induced by type I interferon (IFN), double-stranded RNA and virus infection. Here, we investigated IFIT1 expression in human umbilical vein endothelial cells (HUVECs) and in human bronchus epithelial cells (BEAS-2Bs) induced by the H9N2 virus and inactivated viral particle at different time points. We also investigated the effect of H9N2 virus and viral particle infection on $IFN-{\alpha}/{\beta}$ production, and assessed whether hemagglutinin or neuraminidase protein induced IFIT1 expression. Results showed that both H9N2 virus infection and viral particle inoculation induced the expression of IFIT1 at mRNA and protein levels in the two cell lines. Hemagglutinin or neuraminidase protein binding alone is not sufficient to induce IFIT1 expression. Surprisingly, the expression patterns of IFIT1 in response to H9N2 virus and viral particles in the two cell lines were opposite, and production kinetics of $IFN-{\alpha}/{\beta}$ also differed. An additional finding was that induction of IFIT1 in response to H9N2 virus infection or viral particle inoculation was more sensitive in HUVECs than in BEAS-2Bs. Our data offers new insight into the innate immune response of endothelial cells to H9N2 virus infection.

• 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.

• Journal of Microbiology and Biotechnology
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• v.23 no.8
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• pp.1159-1166
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• 2013

Orientia tsutsugamushi, a gram-negative bacterium, causes severe acute febrile illness in humans. Despite this danger, the route of infection, infectivity, and protective mechanisms of the host's immune response to O. tsutsugamushi are unclear. Dendritic cells (DCs) are one of the most important cell types in bridging the innate and adaptive immune responses. In this study, we observed that O. tsutsugamushi infects and replicates in monocyte-derived DCs (MODCs). During infection and replication, the expressions of the cytokines IL-12 and TNF-${\alpha}$, as well as the co-stimulatory molecules CD80, CD83, CD86, and CD40, were increased in MODCs. When O. tsutsugamushi-treated MODCs were co-cultured with autologous $CD4^+$ T cells, they enhanced production of IFN-${\gamma}$, a major Th1 cytokine. Collectively, our results show that O. tsutsugamushi can replicate in MODCs and can simultaneously induce MODC maturation and increase proinflammatory cytokine levels in MODCs that subsequently activate $CD4^+$ T cells.

• Journal of Life Science
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• v.19 no.2
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• pp.284-288
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• 2009

The innate immune system is important for the first line of host defence against infectious agents, which have penetrated the mechanical barriers. Mannose-binding lectin (MBL or mannan-binding protein, MBP) is a serum protein that is synthesized in the liver as a part of the acute phase response. MBL binds to carbohydrate structures presented by a wide range of pathogenic bacteria, viruses, fungi, and parasites. MBL is synthesized as a monomer that has a carboxy-terminal carbohydrate recognition domain, a neck region and a collagen region. Low MBL level was reported to be the most frequent immuno-deficiency syndrome. Although extensive studies have yielded detailed information on the structure of MBL, functions of the MBL complex are not fully understood yet. We, here, present cloning process of MBL cDNA from the rat liver and production of truncated recombinant MBL protein using a bacterial expression system in order to produce anti-MBL polyclonal antibody. Anti-MBL polyclonal antibody was raised in a New Zealand rabbit and its affinity was tested against recombinant protein using western blot technique. MBL cDNA, recombinant protein and anti-MBL antibody could be used as great arsenals to dissect cellular biochemistry of MBL.

• Journal of Life Science
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• v.32 no.1
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• pp.36-43
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• 2022

Mucosal immunity is a well-designed defense system that builds precise and dynamic relationships against pathogens, and the gastrointestinal tract is the most important organ with this system, acting as a guardian at the forefront of its activity. Salmonella spp. cause food poisoning, entering the body orally and mainly invading the Peyer's patches of the small intestine. Although Salmonella strains share similar mechanisms for inducing innate immunity, different serotypes may have different effects on the intestinal mucosa due to host specificities and pathogenicity. In this study, we evaluated the effects of Salmonella enteritidis infections in mouse intestine and observed significantly reduced dose-dependent survival rates in a challenge test. Flow cytometry data showed no significant differences in intestinal immune cell populations, although histology indicated increased mucin production and decreased goblet cell counts in the Salmonella-treated groups. Furthermore, Claudin expression was significantly decreased in the samples with Salmonella. To investigate the relationship between S. enteritidis infection and inflammatory response, dextran sodium sulfate (DSS) was administered after infection and the results indicate lower survival rate after DSS treatment. In conclusion, we were able to identify the optimal concentration of S. enteritidis to modulate the intestinal mucosal immunity of mice and inflammatory response.

• Journal of Animal Science and Technology
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• v.49 no.2
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• pp.225-238
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• 2007

In this study, the effects of dietary krill meal levels on cellular immunity in LPS-injected broiler chicks was evaluated. One day-old male broiler chicks(Ross) were fed on the experimental basal meal(0.0% krill meal), or diets containing 0.5%, 1.0% and 2.0% krill for 3 weeks, and the acute phase response was activated by intraperitoneally injection of Salmonella typhimurium lipopolysaccharide(LPS) 3 times at 9, 11, and 13 days of age. 1. Acute phase response induced a significant reduction in(p<0.05) daily weight gain and feed intake, and increases in liver and spleen weight. However, it was not affected by dietary krill meal levels. 2. The krill meal diets reduced TNF-α activity as compared to the basal diet after 24 hours (acute phase response) and 1 week(recovery from the acute phase response) following LPS injection (p<0.05). The acute phase response induced a significant increase(p<0.05) in TNF-α activity relative to the control in chicks fed on a basal diet, but this was also unaffected by dietary krill meal levels. 3. Acute phase response-mediated ovotransferrin levels(relative to what was measured in the control bird) were increased in birds fed on the basal, 1.0% and 2.0% krill diets, and were reduced in birds fed on the 0.5 % krill diet. 4. In LPS-injected chicks, 1.0% and 2.0% krill meal diets induced a significant reduction in(p<0.05) the Con A-induced proliferation of PBMC and splenocytes relative to what was observed in the chicks fed on a 0.5% krill diet, whereas the splenocytes proliferated in a linear fashion with the krill levels in the diets of the control birds. The results showed that the dietary levels of krill meal reduced TNF-α activity in the blood and also influenced blood ovotransferrin levels and the proliferation of PBMC and splenocytes, and krill meal is considered to be associated with both innate and cellular immunity in broiler chicks.