• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1437-1443
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• 2016

Background: We investigated four factors, height, weight gain since age 20, physical activity, and alcohol drinking, for associations with risk of breast cancer (BC) according to menopausal status, using the latest data of the Japan Collaborative Cohort Study (JACC Study). Materials and Methods: We confined the analysis to 24 areas available of cancer incidence information, excluding women with a previous diagnosis of BC. Baseline data were collected from 38,610 (9,367 premenopausal, and 29,243 postmenopausal) women during 1988 and 1990. The study subjects were followed-up at the end of 2009, and 273 (84 premenopausal, and 189 postmenopausal) cases of BC were newly diagnosed in 501,907 person-years. The Cox model was used to estimate a hazards ratio (HR) and its 95% confidence interval (CI) of BC risk. Results: As a result of the multivariate analysis adjusting for age at baseline survey, age at menarche, number of live births, and, age at first delivery, weight gain since age 20 of 6.7 kg-9.9 kg, and ${\geq}10.0kg$ were significantly associated with increased risk for postmenopausal BC (HR=2.48, 95% CI 1.40-4.41, and, HR=2.94, 95% CI 1.84-4.70, respectively). Significantly increased trend of BC risk was also observed in weight gain since age 20 (p for trend, p<0.001). Amount of ethanol intake per day${\geq}15.0g$ was significantly associated with increased risk for postmenopausal BC in the multivariable-adjusted analysis (HR=2.74, 95% CI 1.32-5.70). Conclusions: Higher weight gain in adulthood and larger amounts of ethanol intake were significantly associated with increased risk of BC in Japanese postmenopausal women. None of the investigated factors were significantly associated with BC risk in Japanese premenopausal women.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5721-5727
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• 2014

Objectives: To evaluate the performance of clustering methods used in the prognostic assessment of categorical clinical data for hepatocellular carcinoma (HCC) patients in China, and establish a predictable prognostic nomogram for clinical decisions. Materials and Methods: A total of 332 newly diagnosed HCC patients treated with hepatic resection during 2006-2009 were enrolled. Patients were regularly followed up at outpatient clinics. Clustering methods including the Average linkage, k-modes, fuzzy k-modes, PAM, CLARA, protocluster, and ROCK were compared by Monte Carlo simulation, and the optimal method was applied to investigate the clustering pattern of the indices including platelet count, platelet/lymphocyte ratio (PLR) and serum aspartate aminotransferase activity/platelet count ratio index (APRI). Then the clustering variable, age group, tumor size, number of tumor and vascular invasion were studied in a multivariable Cox regression model. A prognostic nomogram was constructed for clinical decisions. Results: The ROCK was best in both the overlapping and non-overlapping cases performed to assess the prognostic value of platelet-based indices. Patients with categorical platelet-based indices significantly split across two clusters, and those with high values, had a high risk of HCC recurrence (hazard ratio [HR] 1.42, 95% CI 1.09-1.86; p<0.01). Tumor size, number of tumor and blood vessel invasion were also associated with high risk of HCC recurrence (all p< 0.01). The nomogram well predicted HCC patient survival at 3 and 5 years. Conclusions: A cluster of platelet-based indices combined with other clinical covariates could be used for prognosis evaluation in HCC.

• Gut and Liver
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• v.12 no.6
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• pp.682-693
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• 2018

Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.113-120
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• 2022

We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E₂ and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

• Journal of Life Science
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• v.29 no.6
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• pp.724-734
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• 2019

The present study investigated the cytotoxicity of particulate matter (PM) derived from car air filter (outdoor PM) and home cleaner filter (indoor PM) in the various human cell lines. Each outdoor and indoor PM were harvested by ethanol extraction method, subsequently sieved with 10 um filter paper, sterilized with autoclave and added to culture media. The half maximal inhibitory concentration ($IC_{50}$) values was significantly (p<0.05) lower in the outdoor PM, compared with indoor PM, and the significantly (p<0.05) higher $IC_{50}$ values were observed in the cancer cell lines (A-549 lung adenocarcinoma and AGS stomach adenocarcinoma), than those of normal MRC-5 fibroblasts and dental papilla tissue derived-mesenchymal stem cells (DSC). After being exposed to $100{\mu}g/ml$ outdoor PM for 7 days, the population doubling time (PDT) was significantly (p<0.05) increased in especially MRC-5 and DSC cell lines, compared with untreated cell lines. Further, the expression of senescence-associated ${\beta}$-galactosidase activity was up-regulated in all the cells exposed to outdoor PM than those of untreated control. Besides, the expression level of inflammation-associated genes, such as cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) was found to be significantly (p<0.05) increased in the outdoor PM-treated cell lines than those of untreated cell lines. Our results showed that PM induces the cytotoxicity via arrest of cell growth, cell damage and inflammation response.

• Journal of Microbiology and Biotechnology
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• v.30 no.10
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• pp.1458-1466
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• 2020

Oligomeric proanthocyanidins (OPCs), classified as condensed tannins, have significant antioxidation, anti-inflammation and anti-cancer effects. This study was performed to investigate the anti-inflammatory effects of OPCs and the mechanism underlying these effects in lipopolysaccharide (LPS)-stimulated bovine mammary epithelial cells (MAC-T). Real-time PCR and ELISA assays indicated that OPC treatment at 1, 3 and 5 ㎍/ml significantly reduced the mRNA and protein, respectively, of oxidant indicators cyclooxygenase-2 (COX-2) (p < 0.05) and inducible nitric oxide synthase (iNOS) (p < 0.01) as well as inflammation cytokines interleukin (IL)-6 (p < 0.01), IL-1β (p < 0.01) and tumor necrosis factor-α (TNF-α) (p < 0.05) in LPS-induced MAC-T cells. Moreover, OPCs downregulated LPS-induced phosphorylation of p65 and inhibitor of nuclear factor kappa B (NF-κB) (IκB) in the NF-κB signaling pathway (p < 0.01), and they inhibited p65 translocation from the cytoplasm to the nucleus as revealed by immunofluorescence test and western blot. Additionally, OPCs decreased phosphorylation of p38, extracellular signal regulated kinase and c-jun NH₂-terminal kinase in the MAPK signaling pathway (p < 0.01). In conclusion, the anti-inflammatory and antioxidant activities of OPCs involve NF-κB and MAPK signaling pathways, thus inhibiting expression of pro-inflammatory factors and oxidation indicators. These findings provide novel experimental evidence for the further practical application of OPCs in prevention and treatment of bovine mastitis.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.213-220
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• 2023

The most common skin disease, acne, often occurs in adolescence, but it is also detected/observed in adults due to air pollution and drug abuse. One of the causative agents of acne, Cutibacterium acnes (C. acnes) plays a role in the development of skin acne by inducing inflammatory mediators. Torreya nucifera (TN) is an evergreen tree of the family Taxaceae, having well reported antioxidant, anti-proliferative, liver protection, and nerve protection properties. Improvement of these bioactive properties of natural products is one of the purposes of natural product chemistry and pharmaceuticals. We believe biorenovation could be one improvement strategy that utilizes microbial metabolism to produce unique derivatives having enhanced bioactivity. Therefore, in this study, the C. acnes-induced RAW264.7 inflammation model was used to evaluate the anti-inflammatory activity of the biorenovated Torreya nucifera product (TNB). The results showed improved viability of TNB-treated cells compared to TN-treated cells in the concentration range of 50, 100, and 200 ㎍/mL. At non-toxic concentrations, TNB inhibited the production of nitric oxide and prostaglandin E2 by suppression of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. TNB also attenuated the expression of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α induced by C. acnes. Furthermore, TNB inhibited the nuclear factor-κB signaling pathway, a transcription factor known to regulate inflammatory mediators. Based on these results, this study suggests the potential of using TNB as natural material for the treatment of acnes and thus, supporting our postulation of biorenovation as an bioactivity improvement strategy.

• Journal of Life Science
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• v.29 no.11
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• pp.1218-1226
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• 2019

The white-spotted flower chafer Protaetia brevitarsis seulensis is a medicinally beneficial and important edible insect species. We previously performed an in silico analysis of the Protaetia brevitarsis seulensis transcriptome to identify putative antimicrobial peptides and then tested their antimicrobial and hemolytic activities. These peptides had potent antimicrobial activities against bacteria and yeast without inducing hemolysis. In the present study, the cationic antimicrobial peptide, protaetiamycine 2, was selected for further assessment of its anti-inflammatory properties in mouse macrophage Raw264.7 cells. Protaetiamycine 2 treatment of Raw264.7 cells suppressed LPS-induced nitric oxide production and reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2, as determined by real-time PCR and western blotting. The expression of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) was also attenuated through the MAPKs and $NF-{\kappa}B$ signaling. We also confirmed that protaetiamycine 2 bound to bacterial cell membranes by a specific interaction with LPS. Collectively, these data obtained from LPS-induced Raw264.7 cells indicated that protaetiamycine 2 could have both antimicrobial and anti-inflammatory properties.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.659-670
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• 2017

Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS ($1{\mu}g/kg$) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, and $IL-1{\alpha}$ expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.1
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• pp.63-71
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• 2004

The human skin is constantly exposed to environmental irritants such as ultraviolet, smoke, chemicals. Free radicals and reactive oxygen species (ROS) caused by these environmental facts play critical roles in cellular damage. These irritants are in themselves damaging to the skin structure but they also participate the immensely complex inflammatory reaction. The purpose of this study was to investigate the skin cell protective effect of Juniperus chinensis xylem extract on the UV and SLS-induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. We found that Juniperus chinensis xylem extracts had potent radical scavenging effect by 98％ at 100 $\mu\textrm{g}$/mL. Fluorometric assays of the proteolytic activities of matrix metalloproteinase-l(MMP-1, collagenase) were performed using fluorescent collagen substrates. UV A induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97％ at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79％ at 25 $\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. In this test Juniperus chinensis decreased expression of interleukin 6 about 30％. Expression of prostaglandin E$_2$, (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay (EIA) using PGE$_2$ monoclonal antibody. At the concentrations of 5-50 $\mu\textrm{g}$/mL of the extracts, the production of PGE$_2$ by HaCaT keratinocytes (24 hours after 10 mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p〈0.05). The viability of cultured HaCaT keratinocytes was significantly reduced at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB irradiation, but the presence of these extracts improved cell viability comparing to control after UVB irradiation. We also investigated the protective effect of this extract in sodium lauryl sulfate (SLS)-induced irritant skin reactions from 24 hour exposure. Twice a day application of the extract for reducing local inflammation in human skin was done. Irritant reactions were assessed by various aspects of skin condition, that is, erythema (skin color reflectance) and transepidermal water loss (TEWL). After 5 days the extract was found to reduce SLS-induced skin erythema and improve barrier regeneration when compared to untreated symmetrical test site. In conclusion, our results suggest that Juniperus chinensis can be effectively used for the prevention of UV and SLS-induced adverse skin reactions such as radical production, inflammation and skin cell damage.