• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5361-5365
• /
• 2013

The objective of this study was to evaluate the influence of a genetic variant in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) risk. This case-control study was conducted in a Chinese population of 645 HCC cases and 658 cancer-free controls. The genotype of the c.3751G>A genetic variant in the MDR1 gene was investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Our data demonstrated significantly differences detected in the allelic and genotypic frequencies between HCC cases and those of cancer-free controls. Association analyses indicated that there were statistically increased risk of HCC in the homozygote comparison (AA versus (vs.) GG: OR=2.22, 95% CI 1.51-3.27, ${\chi}^2$=16.90, P<0.001), dominant model (AA/GA vs. GG: OR=1.25, 95% CI 1.00-1.55, ${\chi}^2$=3.98, P=0.046), recessive model (AA vs. GA/GG: OR=2.14, 95% CI 1.47-3.09, ${\chi}^2$=16.68, P<0.001) and allele comparison (A vs. G: OR=1.33, 95% CI 1.13-1.57, ${\chi}^2$=11.66, P=0.001). The allele-A and genotype-AA may contribute to HCC susceptibility. These preliminary findings suggest that the c.3751G>A genetic variant in the MDR1 gene is potentially related to HCC susceptibility in a Chinese Han population, and might be used as a molecular marker for evaluating HCC susceptibility.

• Proceedings of the Korea Society of Environmental Toocicology Conference
• /
• 2002.10a
• /
• pp.156-156
• /
• 2002

The goal of this study is to develop a biomarker used in monitoring abnormal behaviors of Japanese medaka (Oryzias latipes) as a model organism caused by hazardous chemicals that are toxic and persistent in the ecosystem. A widely used insecticide, diazinon (O, O-diethyl O- (2-isopropyl-4-methyl-6-pyrimidinyl) phosphorothioate), is highly neurotoxic to fish, and it is also well known that it causes vertebral malformation and behavioral changes of fish at relatively low concentrations. The fish behaviors were observed on a real time basis using an image processing and automatic data acquisition system. The genes potentially involved in the abnormal behaviors were cloned using suppression subtractive hybridization (SSH) technique. The untreated individuals showed common behavioral characteristics. When the test fish was affected by diazinon at a concentration of 0.1 and 1 ppm, some specific patterns were observed in its behavioral activity and locomotive tracks. The typical patterns were enhanced surfacing activity, opercular movement, erratic movement, tremors and convulsions as reported previously. The number of genes up-regulated tty diazinon treatment were 97 which includes 27 of unknown genes. The number of down-regulated genes were 99 including 60 of unknown genes. These gene expression patterns will be analyzed by the artificial neural networks such as self organization map (SOM) and multilayer perceptron (MLP), revealing the role of genes responsible for the behaviors. These results may provide molecular biological and neurobehavioral bases of a biomonitoring system for diazinon using a model organism such as fish.

• Molecules and Cells
• /
• v.38 no.5
• /
• pp.452-456
• /
• 2015

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals ($BMI{\geq}30kg/m^2$) showed significantly increased hypermethylation for IL6 gene compared to normal weight ($BMI<23kg/m^2$) and overweight sample ($23kg/m^2{\leq}BMI<30kg/m^2$) (P = 0.034 and P = 0.026). However there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

• Molecular & Cellular Toxicology
• /
• v.2 no.3
• /
• pp.193-201
• /
• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• Mass Spectrometry Letters
• /
• v.5 no.1
• /
• pp.16-23
• /
• 2014

Liquid chromatography based mass spectrometry (LC-MS) is a key technology for analyzing highly complex and dynamic proteome samples. With highly accurate and sensitive LC-MS analysis of complex proteome samples, efficient data processing is another critical issue to obtain more information from LC-MS data. A typical proteomic data processing starts with protein database search engine which assigns peptide sequences to MS/MS spectra and finds proteins. Although several search engines, such as SEQUEST and MASCOT, have been widely used, there is no unique standard way to interpret MS/MS spectra of peptides. Each search engine has pros and cons depending on types of mass spectrometers and physicochemical properties of peptides. In this study, we describe a novel data process pipeline which identifies more peptides and proteins by correcting precursor ion mass numbers and unifying multi search engines results. The pipeline utilizes two open-source software, iPE-MMR for mass number correction, and iProphet to combine several search results. The integrated pipeline identified 25% more proteins in mouse epididymal adipose tissue compared with the conventional method. Also the pipeline was validated using control and colitis induced colon tissue. The results of the present study shows that the integrated pipeline can efficiently identify increased number of proteins compared to the conventional method which can be a breakthrough in identification of a potential biomarker candidate.

• Journal of Gastric Cancer
• /
• v.23 no.2
• /
• pp.340-354
• /
• 2023

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

• Journal of Ginseng Research
• /
• v.48 no.2
• /
• pp.211-219
• /
• 2024

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0-2 × 10⁹ particles/mL), and followed by UVB irradiation or H₂O₂ exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C-O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.6
• /
• pp.1214-1221
• /
• 2024

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. β-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

• Tuberculosis and Respiratory Diseases
• /
• v.87 no.3
• /
• pp.398-408
• /
• 2024

Background: Lung cancer is one of the most dangerous cancers and tuberculosis is one of the deadliest infectious diseases in the world. Many studies have confirmed the connection between lung cancer and tuberculosis, and also the microRNAs (miRNAs) that play a major role in the development of these two diseases. This study aims to use different databases to find effective miRNAs and their role in different genes in lung and tuberculosis diseases. It also aims to determine the role of miR-34a and miR-182 in lung cancer and tuberculosis. Methods: Using the Gene Expression Omnibus (GEO) database, the influential miRNA databases were studied in the two diseases. Finally, considering bioinformatics results and literature studies, two miR-34a and miR-182 were selected. The role of these miRNAs and their target genes was carefully evaluated using bioinformatics. The expression of miRNAs in the plasma of patients with lung cancer and tuberculosis and healthy individuals was investigated. Results: According to the GEO database, miR-34a and miR-182 are miRNAs that affect tuberculosis and lung cancer. By checking the miRBase, miRcode, DIANA, miRDB, galaxy, Kyoto Encyclopedia of Genes and Genomes databases, the role of these miRNAs on genes and different molecular pathways and their effect on these miRNAs were mentioned. The results of the present study showed that the expression of miR-34a and miR-182 was lower than that of healthy people. The p-value for miR-182 was <0.0001 and for miR-34a was 0.3380. Conclusion: Reducing the expression pattern of these miRNAs indicates their role in lung cancer and tuberculosis occurrence. Therefore, these miRNAs can be used as a biomarker for prognosis, diagnosis, and treatment methods.

• Proceedings of the Korean Aquaculture Society Conference
• /
• 2003.10a
• /
• pp.43-43
• /
• 2003

EST analysis was performed to identify stress-responsive and immune-related genes from rock bream (Oplegnathus fasciatus). cDNA libraries were constructed with liver and randomly chosen 624 clones were subjected to automated sequence analysis. Of 624 clones sequenced in total, approximately 15% of ESTs was novel sequences (no match to GenBank) or sequences with high homology to hypothetical/unknown genes. The bioinforamtic sequence analysis including functional clustering, homology grouping, contig assembly with electronic northern and organism matches were carried out. Several potential stress-responsive biomarker and/or immune-related genes were identified in all the tissues examined. It included lectins, ferritins, CP450, proteinase, proteinase inhibitors, anti-oxidant enzymes, various heat-shock proteins, warm temperature acclimation protein, complements, methyltransferase, zinc finger proteins, lysozymes, macrophage maturation associated protein, and others. This information will offer new possibilities as fundamental baseline data for understanding and addressing their molecular mechanism involved in host defense and immune systems of this species.