• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.73-81
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• 2023

Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3973-3980
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• 2014

Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX. In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostate adenocarcinoma in the Pakistani population (p=0.000).

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3555-3559
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• 2013

Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factors for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variation and the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infected with HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249S mutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP) in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basal core promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group. R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was not significantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations was independently associated with the risk of HCC in Thai patients.

• Journal of The Korean Society of Agricultural Engineers
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• v.53 no.6
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• pp.111-119
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• 2011

The main objective of this study was to evaluate the effects of control-release fertilizer (CRF) on pollutant loadings from a small watershed. The Baran watershed, 386 ha in size, was selected as the study site, and the AGNPS (Agricultural Non-point Source Pollution) model was used to evaluate the effects of fertilizer types. Digital maps of digital elevation (DEM), slope distribution, channel, flow direction, landuse, soil, and curve number were extracted from the study watershed. Model parameters related to hydrology and water quality were calibrated and validated by comparing model predictions with the observed data collected for 2 years (1999 to 2000). Calibration and validation resulted in $R^2$ values of 0.75-0.91 for all the water quality parameters. All the paddy fields (21.2 %) of the study watershed were sprayed by either CRF or NPK (standard fertilizer). In CRF application, total nitrogen (TN) load was 4.9% less than NPK application, however total phosphorus (TP) load was 0.7 % more than NPK application. In CRF application, considering only paddy fields in the study area, TN load was 38.7 % less than NPK application. Using CRF in paddy fields could be one of the ways to reduce pollutant loadings from agricultural watersheds, however, in order to confirm it, more researches about effects of using CRF are necessary.

• Journal of Animal Science and Technology
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• v.53 no.6
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• pp.549-561
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• 2011

Livestock wastewater is being discharged without treatment from Hasen's pig farm cluster in WangGoong (WG) area into the Iksan Stream, eventually flowing into the ManGyung (MG) at the upstream junction. Although it is well known that before discharge, wastewater must satisfy the pig slurry discharge standards; because of ongoing remodeling, proper treatment is not being performed. According to public records, wastewater from the WG pig farm cluster is responsible for 3.6% of MG River pollution and 2.0% of the SaeManGuem (SMG) Reservoir pollution. As a result, upstream water treatment quality has become primary concern for development of the SMG project. All physicochemical constituents and pathogenic microbes, such as chemical oxygen demand ($COD_{Cr}$), biochemical oxygen demand ($BOD_5$), total suspended solids (TSS), total nitrogen (TN), total phosphorous (TP), fecal coliforms, Escherichia coli and Salmonella at the effluent of WG Plant (S-1) exceed the effluent standards. This is mainly due to insufficient wastewater treatment: the WG Plant is under renovation to increase water purification efficiency. By comparing the water quality at the S-7 junction, where the the Iksan Stream (pig farms) and the Wanggoong Stream (no pig farms) merge, it is clear that farming facilities and improper treatment can critically affect surrounding water quality. While it is clear throughout this study that the level of all physicochemical parameters and pathogenic microbes along the Stream decreased due to sedimentation, biodegradation and/or dilution. An alarming problem was discovered: the existence of pathogenic microbe count(E coli, Salmonella) in the lagoon wastewater and the stream water. Not only were high concentrations of these pathogens themselves found, but the potential existence of more serious pathogens could rise to more dangerous conditions.

• Journal of The Korean Society of Agricultural Engineers
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• v.57 no.5
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• pp.129-137
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• 2015

The objective of this study was to test the non-point source pollution (NPS) control by the vegetated ridge and silt fence through field monitoring. The experiment plots were established with three sizes which are 5 m width by 22 m length with 8 %, 3 % slope and 15m width by 15 m length with 6 % slope. Flumes with the floating type stage gages were installed at the outlet of each plot to monitor the runoff. For a rainfall monitoring, tipping bucket rain gage was installed within the experiment site. Water quality samples were monitored during the heavy rainfall occurred. The amount of rainfall from 4 monitored events ranged from 27.6 mm to 130 mm. The runoff reduction rate could vary depending on slope, soil, crop growth condition, rainfall amount, rainfall intensity, antecedent moisture condition, and many other factors. The runoff from vegetated ridge and silt fence treatment plots was 24.05 % and -8.28 % lower than that from control plot, respectively. The monitoring results showed that the average pollution loads reduced by vegetated ridge compared to control were BOD 36.62~53.60 %, SS 40.41~73.71 %, COD 39.34~56.41 %, DOC 49.08~53.67 %, TN 26.74~67.23 %, and TP 52.72~91.80 %; by silt fence compared to control were SS 41.73 %, COD 1.93 %, and TN 2.38 %. The paired t-test result indicated that the vegetated ridge and silt fence were statistically significant effect in SS load reduction, with a 5 % significant level. Monitored results indicated that vegetated ridge and silt fence were both effective to reduce the pollutant from the field surface runoff.

• Journal of The Korean Society of Agricultural Engineers
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• v.53 no.4
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• pp.29-37
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• 2011

Effect of rice straw mat and wood shaves on the reduction of runoff and nonpoint source (NPS) pollution loads from field plots were experimentally studied. Three runoff plots of $5{\times}22$ m in size and 3 % in slope were prepared on a loamy sand field. Each plot was equipped with a flume to measure runoff and collect water samples. Experimental treatments of surface cover were bare, wood shaves (1,000 kg/ha) and rice straw mat cover (3,000 kg/ha). Under radish was cultivation. During the growing season of the radish, three rainfall-runoff events were monitored. Effect of wood shaves and straw mat cover on runoff reduction was 4~30 % and 33~75 % respectively compared to control. The effect on NPS pollution reduction was 36.8 and 64.3 % in BOD, 41.1 and 80.8 % in SS, 34.0 and 56.1 % in TP and 28.0 and 56.6 % in TN respectively. It was analyzed that the reduction of runoff and NPS pollution were mainly contributed by the decrease of rainfall energy impact and flow velocity and the increase of infiltration due to the surface cover materials. Rice straw mat showed very stable soil cover while large portion of wood shaves were lost during heavy storm events. It was concluded that straw mat was an efficient cover material to reduce NPS pollution from upland fields.

• Journal of the Institute of Electronics and Information Engineers
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• v.53 no.2
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• pp.47-52
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• 2016

The used digital images in the smart device and small displayer has been a downscaled image. In this paper, the detection of the downscaling image forgery is proposed using the feature vector according to the pixel value's gradients. In the proposed algorithm, AR (Autoregressive) coefficients are computed from pixel value's gradients of the image. These coefficients as the feature vectors are used in the learning of a SVM (Support Vector Machine) classification for the downscaling image forgery detector. On the performance of the proposed algorithm, it is excellent at the downscaling 90% image forgery compare to MFR (Median Filter Residual) scheme that had the same 10-Dim. feature vectors and 686-Dim. SPAM (Subtractive Pixel Adjacency Matrix) scheme. In averaging filtering ($3{\times}3$) and median filtering ($3{\times}3$) images, it has a higher detection ratio. Especially, the measured performances of all items in averaging and median filtering ($3{\times}3$), AUC (Area Under Curve) by the sensitivity and 1-specificity is approached to 1. Thus, it is confirmed that the grade evaluation of the proposed algorithm is 'Excellent (A)'.

• Journal of Cancer Prevention
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• v.22 no.4
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• pp.234-240
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• 2017

Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs. Bioinformatic analysis was performed using various tools. Results: Alterations in several genes were implicated in lung cancer resulting from exposure to radon indoors, namely those in epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), NK2 homeobox 1 (NKX2.1), phosphatase and tensin homolog (PTEN), chromodomain helicase DNA binding protein 7 (CHD7), discoidin domain receptor tyrosine kinase 2 (DDR2), lysine methyltransferase 2C (MLL3), chromodomain helicase DNA binding protein 5 (CHD5), FAT atypical cadherin 1 (FAT1), and dual specificity phosphatase 27 (putative) (DUSP27). Conclusions: While these genes might regulate the carcinogenic pathways of radioactivity, further analysis is needed to determine whether the genes are indeed completely responsible for causing lung cancer in never smokers exposed to residential radon.

• BMB Reports
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• v.46 no.5
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• pp.270-275
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• 2013

It is essential to analyze rare mutations in many fields of biomedical research. However, the detection of rare mutations is usually failed due to the interference of predominant wild-type DNA surrounded. Herein we describe a sensitive and facile method of detecting rare point mutation on the basis of allele-specific amplification in emulsion PCR. The identification and selective amplification of rare mutation are accomplished in one-pot reaction. The allele-specific primers coupled on magnetic beads allow the exclusive amplification and enrichment of the mutant amplicons. The productive beads bearing mutant amplicons are subsequently stained with the fluorescent dyes. Thus, the rare point mutations with a percentage as low as 0.1%, can be detected by fluorescent analysis. The relative percentages of mutation among different samples can be roughly accessed by counting the fraction of fluorescent positive beads through flow cytometry.