• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6145-6150
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• 2014

Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2979-2986
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• 2014

Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

• Journal of Haehwa Medicine
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• v.21 no.1
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• pp.11-21
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• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• BMB Reports
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• v.44 no.2
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• pp.135-139
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• 2011

Chronic alcohol consumption contributes to numerous diseases, including cancers, cardiovascular diseases, and liver cirrhosis. Epidemiological studies have shown that excessive alcohol consumption is a risk factor for dementia. Along this line, Alzheimer's disease (AD) is the most common form of dementia and is caused by the accumulation of amyloid-$\beta$ ($A{\beta}$ plaques in neurons. In this study, we hypothesized that chronic ethanol consumption is associated with pathological processing of APP in AD. To investigate the relationship between chronic alcohol consumption and $A{\beta}$ production, brain samples from rats fed an alcohol liquid diet for 5 weeks were analyzed. We show that the expression levels of APP, BACE1, and immature nicastrin were increased in the cerebellum, hippocampus, and striatum of the alcohol-fed group compared to the control group. Total nicastrin and PS1 levels were induced in the hippocampus of alcohol-fed rats. These data suggest that the altered expression of APP and $A{\beta}$-producing enzymes possibly contributes to the chronic alcohol consumption-mediated pathogenesis of AD.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.109-116
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• 2020

BACKGROUND/OBJECTIVES: Excessive intake of simple sugars induces obesity and increases the risk of inflammation. Thus, interest in alternative sweeteners as a sugar substitute is increasing. The purpose of this study was to determine the effect of saccharin on inflammation in 3T3-L1 adipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes. The adipocytes were treated with saccharin (0, 50, 100, and 200 ㎍/mL) for 24 h. Inflammation was induced by exposure of treated adipocytes to lipopolysaccharide (LPS) for 18 h and cell proliferation was measured. The concentration of nitric oxide (NO) was measured by using Griess reagent. Protein expressions of nuclear factor kappa B (NF-κB) and inhibitor κB (IκB) were determined by western blot analysis. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were determined by real-time PCR. RESULTS: Compared with the control group, the amount of NO and the mRNA expression of iNOS in the LPS-treated group were increased by about 17.6% and 46.9%, respectively, (P < 0.05), and those parameter levels were significantly decreased by saccharin treatment (P < 0.05). Protein expression of NF-κB was decreased and that of IκB was increased by saccharin treatment (P < 0.05). Saccharin decreased the mRNA expression of COX-2 and the inflammation cytokines (IL-1β, IL-6, MCP-1, and TNF-α) (P < 0.05). CONCLUSIONS: The results of this study suggest that saccharin can inhibit LPS-induced inflammatory responses in 3T3-L1 adipocytes via the NF-κB pathway.

• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1304-1309
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• 2005

The production of therapeutic proteins for human diseases in plants results in many economic benefits, including reduced risk of animal virus contamination, high yields, and reduced production and storage costs. Human cytokines, interleukin-11 (hlL-11) and granulocyte-macrophage colony-stimulating factor (hGM-CSF), cDNAs were introduced into rice or tobacco, using either the maize ubiquitin promoter or the 35S promoter. The primary hIL-11 transgenic rice plants exhibited stunted growth and a sterile phenotype, whereas the hIL-11 transgenic tobacco plants did not. This suggests that hIL-11 expression in rice disrupts the normal growth and development of the plant. The regeneration efficiency of rice calli transformed with hGM-CSF was found to be approximately a quarter of that seen with the hIL-11, suggesting that hGM-CSF expression is more deleterious to the regeneration of rice calli than is hIL-11. However, the surviving hGM-CSF transgenic rice plants exhibited a normal phenotype of growth. Therefore, it appears that only those transgenic rice lines that expressed the human cytokines in small quantities were able to survive the selection process.

• Nutrition Research and Practice
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• v.14 no.3
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• pp.188-202
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• 2020

BACKGROUND/OBJECTIVES: Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging. MATERIALS/METHODS: The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS: Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS: To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.

• Tuberculosis and Respiratory Diseases
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• v.70 no.6
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• pp.462-473
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• 2011

Background: Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains obscure. There is evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. This study was to determine whether the administration of small interfering RNA (siRNA) targeting PAI-1 or PAI-1 inhibitor to the cigarette smoking extract (CSE)-exposed rat alveolar type II epithelial cells (ATII cells) limits the epithelial-mesenchymal transition (EMT). Methods: ATII cells were isolated from lung of SD-rat using percoll gradient method and cultured with 5% CSE. The EMT was determined from the ATII cells by measuring the real-time RT PCR and western blotting after the PAI-1 siRNA transfection to the cells and after administration of tiplaxtinin, an inhibitor of PAI-1. The effect of PAI-1 inhibitor was also evaluated in the bleomycin-induced rats. Results: PAI-1 was overexpressed in the smoking exposed ATII cells and was directly associated with EMT. The EMT from the ATII cells was suppressed by PAI-1 siRNA transfection or administration of tiplaxtinin. Signaling pathways for EMT by smoking extract were through the phosphorylation of SMAD2 and ERK1/2, and finally Snail expression. Tiplaxtinin also suppressed the pulmonary fibrosis and PAI-1 expression in the bleomycin-induced rats. Conclusion: Our data shows that CSE induces rat ATII cells to undergo EMT by PAI-1 via SMAD2-ERK1/2-Snail activation. This suppression of EMT by PAI-1 siRNA transfection or PAI-1 inhibitor in primary type II alveolar epithelial cells might be involved in the attenuation of bleomycin-induced pulmonary fibrosis in rats.

• Toxicological Research
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• v.30 no.2
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• pp.83-90
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• 2014

An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel aerosolization process, and the mice were exposed to the aerosol for 4 hours. We found that CBNP inhalation exacerbated lung inflammation, as evidenced by histopathology analysis and by the expression levels of interleukin-6 protein, fibronectin, and interferon-${\gamma}$ mRNAs in lung tissues. Notably, fibronectin mRNA expression showed a statistically significant increase in expression after CBNP exposure. These data suggest that the concentration of CBNPs delivered (calculated to be $12.5{\mu}g/m^3$) can aggravate lung inflammation in mice. Our results also suggest that the inhalation of ultrafine particles like PM 2.5 is an impactful environmental risk factor for humans, particularly in susceptible populations with predisposing lung conditions.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.114-119
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• 2006

Benzo[a]pyrene is a representative ecotoxicant in marine environment and a model compound of polycyclic aromatic hydrocarbons, which has an ability to bioaccumulate in aquatic organisms. This study aimed to identify molecular biomarkers suitable for assessing environmental pollution using a microarray technique. We examined the effects of benzo[a]pyrene on gene expressions in the rockfish, Sebastes schlegeli. We constructed the subtractive cDNA library with hepatic RNA from benzo[a]pyrene-exposed and non-exposed control fish. From the library 10,000 candidate clones were selected randomly and cDNA microarray was constructed. We determined benzo[a]pyrene-responsive genes using a high-density microarray. Statistical analysis showed that approximately 400 genes are significantly induced or reduced by benzo[a]pyrene treatment ($2\;{\mu}m$). Especially gene expression changes of 4 candidate clones among the up- or down-regulated genes were investigated in 6, 12 and 24 hr BaP-exposed fish groups. Many methods have been developed to monitor marine environmental status, which depend on quantifying the levels of the toxic components in polluted seawater or on ecological accessing, such as species diversity or richness. However, those methods could not provide information on physiological or genetic changes induced by such environmental stresses. Comparing with the conventional methods, these data will propose that benzo[a]pyrene-responsive genes can be useful for biological risk assessment of polycyclic aromatic hydrocarbons on marine organism at molecular level.