• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.410-418
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• 2021

Helicobacter pylori causes chronic gastritis through cag pathogenicity island (cagPAI), vacuolating cytotoxin A (VacA), lipopolysaccharides (LPS), and flagellin as pathogen-related molecular patterns (PAMPs), which, in combination with the pattern recognition receptors (PRRs) of host cells promotes the expression and secretion of inflammation-causing cytokines and activates innate immune responses such as inflammasomes. To identify useful compounds against H. pylori-associated gastric disorders, the effect of chalcone derivatives to activate the nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was examined in an H. pylori-infected human monocytic THP-1 cell line in this study. Among the five synthetic structurally-related chalcone derivatives examined, 2'-hydroxy-4',6'-dimethoxychalcone (8) and 2'-hydroxy-3,4,5-trimethoxychalcone (12) strongly blocked the NLRP3 inflammasome in H. pylori-infected THP-1 cells. At 10 μM, these compounds inhibited the production of active IL-1β, IL-18, and caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization, but did not affect the expression levels of NLRP3, ASC, and pro-caspase-1. The interruption of NLRP3 inflammasome activation by these compounds was found to be mediated via the inhibition of the interleukin-1 receptor-associated kinase 4 (IRAK4)/IκBα/NF-κB signaling pathway. These compounds also inhibited caspase-4 production associated with non-canonical NLRP3 inflammasome activation. These results show for the first time that certain chalcones could interrupt the activation of the NLRP3 inflammasome in H. pylori-infected THP-1 cells. Therefore, these chalcones may be helpful in alleviating H. pylori-related inflammatory disorders including chronic gastritis.

• Journal of fish pathology
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• v.34 no.1
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• pp.23-29
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• 2021

Interferon regulatory factors (IRFs) are a family of transcription factors essential to the control of antiviral immune response, cell growth, differentiation and apoptosis. IRF10 of zebrafish (Danio rerio) was negative regulation of the interferonΦ1 and 3 response in vitro. In this study, we analyze the induction of in vivo immune response activation from the IRF10 gene of zebrafish and the protective effect against VHSV. As the results, the group inoculated with IRF10 expression vectors, there was no expression of IFNΦ1, suggestion that IRF10 may function as a negative regulator of IRF3, which binds to the IFNΦ1 promoter. And other types of interferon genes (IFNΦ2-4) are thought to have been activated, inducing to the expression of pro-inflammatory cytokine and Mx genes. As the results of challenge test performed at 14 days after inoculation of the expression vectors, the maximum survival rate [50% (1㎍ DNA) and 42.5% (10㎍ DNA)] for IRF10 group were recorded. Meanwhile, the survival rates of pcDNA3.1 and PBS as the control groups were 10% and 15%, respectively. This study suggests that the possibility that activation of IRF10 molecule could be exploited as a VHS control method.

• Journal of Microbiology and Biotechnology
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• v.29 no.7
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• pp.1155-1164
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• 2019

Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 log-fold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-$HDMS^E$) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, $HIF-1{\alpha}$, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including $HIF-1{\alpha}$ signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.

• Journal of Animal Science and Technology
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• v.62 no.6
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• pp.765-776
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• 2020

The retinal degenerative disease, progressive retinal atrophy (PRA) is a major reason of vision impairment in canine population. Canine PRA signifies an inherently dissimilar category of retinal dystrophies which has solid resemblances to human retinis pigmentosa. Even though much is known about the biology of PRA, the knowledge about the intricate connection among genetic loci, genes and pathways associated to this disease in dogs are still remain unknown. Therefore, we have performed a genome wide association study (GWAS) to identify susceptibility single nucleotide polymorphisms (SNPs) of PRA. The GWAS was performed using a case-control based association analysis method on PRA dataset of 129 dogs and 135,553 markers. Further, the gene-set and pathway analysis were conducted in this study. A total of 1,114 markers associations with PRA trait at p < 0.01 were extracted and mapped to 640 unique genes, and then selected significant (p < 0.05) enriched 35 gene ontology (GO) terms and 5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contain these genes. In particular, apoptosis process, homophilic cell adhesion, calcium ion binding, and endoplasmic reticulum GO terms as well as pathways related to focal adhesion, cyclic guanosine monophosphate)-protein kinase G signaling, and axon guidance were more likely associated to the PRA disease in dogs. These data could provide new insight for further research on identification of potential genes and causative pathways for PRA in dogs.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.54 no.2
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• pp.162-169
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• 2021

Global warming has affected the distribution of organisms for decades and has displayed rapid ascent recently. Research into the effects on tropical organisms are vital. Padina boryana is a resourceful marine microalgae in the Maldives Sea in the Laccadive region. A 70% ethanol extraction (PBE) of this seaweed was used to investigate its antioxidant potential. Both in vitro and in vivo models were implemented. PBE exhibited protective potential against H₂O₂ induced apoptosis. ROS levels were suppressed due to PBE. PBE expressed a cytoprotective nature. In vivo experiments involving the zebra fish model conformed its validity. The antioxidant efficacy of PBE was dose dependent. Study outcomes suggest PBE has potential as a novel and valuable marine resource to aid the functional food and cosmeceutical industries.

• International Journal of Oral Biology
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• v.47 no.1
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• pp.1-8
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• 2022

Inflammation is a protective mechanism against pathogens, but if maintained continuously, it destroys tissue structures. Aggregatibacter actinomycetemcomitans is a gram-negative, facultative anaerobic bacterium often found in severe periodontitis. A. actinomycetemcomitans invades epithelial cells and triggers inflammatory response in the immune cells. In this study, we investigated the effect of water-soluble rosehip extract on A. actinomycetemcomitans-induced inflammatory responses. A human monocytic cell line (THP-1) was differentiated to macrophages by phorbol 12-mystristate 13-acetate treatment. The cytotoxic effect of extract was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of extract on bacterial growth were examined by measuring the optical densities using a spectrophotometer. THP-1-derived macrophages were infected A. actinomycetemcomitans after extract treatment, and culture supernatants were analyzed for cytokine production using enzyme-linked immunosorbent assay. Protein expression was measured by western blotting. Extract was not toxic to THP-1-derived macrophages. A. actinomycetemcomitans growth was inhibited by 1% extract. The extract suppressed A. actinomycetemcomitans-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-8 production. It also decreased mitogen-activated protein kinase (MAP kinase) and nuclear factor-κB (NF-κB) phosphorylation. Moreover, the extract inhibited the expression of inflammasome components, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3, Absent in Melanoma 2, and apoptosis associated speck-like protein containing a CARD. And cysteine-aspartic proteases-1 and IL-1β expression were decreased by the extract. In summary, extract suppressed A. actinomycetemcomitans growth and decreased inflammatory cytokine production by inhibiting activation of MAP kinase, NF-κB, and inflammasome signaling. Rosehip extract could be effective in the treatment of periodontal inflammation induced by A. actinomycetemcomitans infection.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.3
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• pp.175-184
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• 2022

Objective: The aim of this study was to evaluate the impacts of platelet-rich plasma (PRP) and conditioned medium (CM) derived from endometrial stromal cells on mouse preantral follicle culture in a two-dimensional system to produce competent mature oocytes for fertilization. Methods: In total, 240 preantral follicles were isolated from female mouse ovarian tissue and divided into four groups. The preantral follicles were isolated three times for each group and then cultured, respectively, in the presence of alpha minimum essential medium (control), PRP, CM, and PRP+CM. The in vitro growth, in vitro maturation, and cleavage percentage of the preantral follicles were investigated. Immunocytochemistry (IHC) was also conducted to monitor the meiotic progression of the oocytes. Additionally, the mRNA expression levels of the two folliculogenesis-related genes (Gdf9 and Bmp15) and two apoptosis-related genes (Bcl2 and Bax) were investigated using real-time polymerase chain reaction. Results: In the PRP, CM, and PRP+CM groups, the preantral follicle maturation (evaluated by identifying polar bodies) were greater than the control group. The cleavage rate in the CM, and PRP+CM groups were also greater than the control group. IHC analysis demonstrated that in each treatment group, meiotic spindle was normal. In the PRP+CM group, the gene expression levels of Bmp15, Gdf9, and Bcl2 were greater than in the other groups. The Bax gene was more strongly expressed in the PRP and control groups than in the other groups. Conclusion: Overall, the present study suggests that the combination of CM and PRP can effectively increase the growth and cleavage rate of mouse preantral follicles in vitro.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.331-341
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• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.23-28
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• 2012

Objectives : Samhwangsashim-tang(SHSST), a mixture of Rhei radix et rhizoma, Scutellariae radix, and Coptidis rhizoma, has been regarded as being able to treat bleeding, gastric discomfort, dry mouth, insomnia and purpura due to Blood Heat. Currently, this herbal formula is applied to gastritis, gastric ulcer, hypertension, atherosclerosis or other types of vascular inflammatory disorders. Methods : We extracted this herbal mixture with 30% ethanol and examined for its effects on systemic inflammatory responses and in vitro macrophage activity. Mice were orally given to SHSST for 7 days and then lipopolysaccharide(LPS) was intraperitoneally injected. Tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) levels in serum were measured 1 h after LPS challenge. Peritoneal macrophages were isolated from thioglycollate-injected mice and used for in vitro cellular activity. Cell death was measured using the MTT method and annexin V/propidium iodide staining. LPS-stimulated signaling molecules necessary for TNF-${\alpha}$ expression were determined by Western blotting. Results : Oral administration of SHSST for 7 days resulted in a significant reduction in LPS-stimulated TNF-${\alpha}$ release into serum. In vitro treatment of SHSST was cytotoxic in a concentration-dependent manner. However, SHSST caused a concentration-dependent reduction in necrosis and increase in apoptosis in mouse peritoneal macrophages. SHSST inhibited the activation of NF-${\kappa}B$, p38 and JNK signaling molecules in response to LPS. Conclusion : Taken together, our results demonstrated that SHSST was effective in lowering LPS-stimulated TNF-${\alpha}$ serum levels, possibly through its modulation of NF-${\kappa}B$, p38 and JNK in macrophages.

• The Korea Journal of Herbology
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• v.30 no.2
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• pp.1-9
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• 2015

Objectives : The present study was conducted to examine whether Toosendan Fructus has an ameliorative effect on diabetes-induced alterations such as oxidative stress and inflammation in the pancreas of non-obese diabetic (NOD) mice, a model of human type I diabetes. Methods : Extracts of Toosendan Fructus (ETF) were administered to NOD mice at three doses (50 mg/kg, 100 mg/kg and 200 mg/kg). Mice at 18 weeks of age were measured glucose tolerance using intraperitoneal glucose tolerance test. After 28 weeks of ETF treatment, glucose, total cholesterol (TC), triglyceride (TG), and proinflammatory cytokines in serum, western blot analyses and a histopathological examination in pancreas tissue, and on the onset of diabetes were investigated. Results : The results showed that levels of glucose, glucose tolerance, TC, TG, interferon-${\gamma}$, interleukin (IL)-1 ${\beta}$, IL-6, and IL-12 in serum were down-regulated, while IL-4, IL-10, SOD, and catalase significantly increased. In addition, ETF improved protein expression of proinflammatory mediaters (such as cyclooxygenase-2, and inducible nitric oxide synthase) and a proapoptotic protein (caspase-3) in the pancreatic tissue. Also, in the groups treated with ETF (100 mg/kg or 200 mg/kg), insulitis and infiltration of granulocytes were alleviated. Conclusions : Based on these results, the anti-diabetic effect of ETF may be due to its anti-inflammatory and antioxidant effect. Our findings support the therapeutic evidence for Toosendan Fructus ameliorating the development of diabetic pancreatic damage via regulating inflammation and apoptosis. Our future studies will be focused on the search for active compounds in these extracts.