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BACKGROUND: Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. RESULTS: We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. CONCLUSIONS: This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.
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Biomarcadores de Tumor , ADN Tumoral Circulante , Neoplasias del Colon , Metilación de ADN , Humanos , Neoplasias del Colon/genética , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/sangre , Metilación de ADN/genética , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Femenino , Masculino , Persona de Mediana Edad , Biopsia Líquida/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Anciano , Detección Precoz del Cáncer/métodos , Epigénesis Genética , Estudios de Casos y Controles , Sensibilidad y Especificidad , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangre , Adulto , PronósticoRESUMEN
This paper introduces the KRISS-Rn4, a high-sensitivity radon monitor with four detection cells, installed within a walk-in type radon calibration chamber at KRISS. The KRISS-Rn4 exhibits enhanced energy resolution through channel-by-channel signal processing and data acquisition. Results reveal that it achieves lower statistical fluctuations and faster response times in monitoring test atmospheres compared to commercial devices.
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Background: Acute myocardial infarction (AMI) is one of the leading causes of death worldwide, and approximately half of AMI-related deaths occur before the affected individual reaches the hospital. The present study aimed to identify and validate genetic variants associated with AMI and their role as prognostic markers. Materials and methods: We conducted a replication study of 29 previously identified novel loci containing 85 genetic variants associated with early-onset AMI using a new independent set of 2,920 Koreans [88 patients with early- and 1,085 patients with late-onset AMI, who underwent percutaneous coronary intervention (PCI), and 1,747 healthy controls]. Results: Of the 85 previously reported early-onset variants, six were confirmed in our genome-wide association study with a false discovery rate of less than 0.05. Notably, rs12639023, a cis-eQTL located in the intergenic region between LINC02005 and CNTN3, significantly increased longitudinal cardiac mortality and recurrent AMI. CNTN3 is known to play a role in altering vascular permeability. Another variant, rs78631167, located upstream of PLAUR and known to function in fibrinolysis, was moderately replicated in this study. By surveying the nearby genomic region around rs78631167, we identified a significant novel locus (rs8109584) located 13â bp downstream of rs78631167. The present study showed that six of the early-onset variants of AMI are applicable to both early- and late-onset cases. Conclusion: Our results confirm markers that can potentially be utilized to predict, screen, prevent, and treat candidate patients with AMI and highlight the potential of rs12639023 as a prognostic marker for cardiac mortality in AMI.
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Early-onset acute myocardial infarction (AMI) may have a higher genetic predisposition than late-onset AMI. The present study aimed to identify and characterize germline variants that affect early-onset AMI using whole-genome sequencing (WGS). We performed a genome-wide association study based on the WGS of 1239 Koreans, including 596 early-onset AMI patients and 643 healthy individuals. Patients with AMI who underwent percutaneous coronary intervention (PCI) caused by atherothrombotic occlusive lesions were included in the study. A total of 29 novel loci were found to be associated with early-onset AMI. These loci are involved in thrombosis, fibrinolysis, inflammation, and lipid metabolism. One of the associated single nucleotide variants (SNVs), rs1614576, located upstream of PRKCB, is known to be associated with thrombus formation. Additionally, the results revealed a novel locus, rs78631167, located upstream of PLAUR which plays a critical role in regulating plasminogen activation and is related to fibrinolysis. The association between early-onset AMI and rs9357455, which is located upstream of PHACTR1 and regulates inflammation in AMI, was found. Moreover, we identified a lipid metabolism related genetic risk locus, rs5072, in the APOA1-AS gene. This study provides new evidence supporting the genetic association between early-onset AMI and thrombosis and fibrinolysis, as well as inflammation and lipid metabolism, by analyzing the whole-genome of 596 patients with early-onset AMI who have been treated with PCI. Our findings highlight potential genetic markers for the prediction and management of AMI, as well as for understanding the etiology of AMI.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Trombosis , Humanos , Infarto del Miocardio/genética , Estudio de Asociación del Genoma Completo , Trombosis/complicaciones , Inflamación , Secuenciación Completa del GenomaRESUMEN
Early detection is critical for minimizing mortality from cancer. Plasma cell-free DNA (cfDNA) contains the signatures of tumor DNA, allowing us to quantify the signature and diagnose early-stage tumors. Here, we report a novel tumor fragment quantification method, TOF (Tumor Originated Fragment) for the diagnosis of lung cancer by quantifying and analyzing both the plasma cfDNA methylation patterns and fragmentomic signatures. TOF utilizes the amount of ctDNA predicted from the methylation density information of each cfDNA read mapped on 6243 lung-tumor-specific CpG markers. The 6243 tumor-specific markers were derived from lung tumor tissues by comparing them with corresponding normal tissues and healthy blood from public methylation data. TOF also utilizes two cfDNA fragmentomic signatures: 1) the short fragment ratio, and 2) the 5' end-motif profile. We used 298 plasma samples to analyze cfDNA signatures using enzymatic methyl-sequencing data from 201 lung cancer patients and 97 healthy controls. The TOF score showed 0.98 of the area under the curve in correctly classifying lung cancer from normal samples. The TOF score resolution was high enough to clearly differentiate even the early-stage non-small cell lung cancer patients from the healthy controls. The same was true for small cell lung cancer patients.
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Carcinoma de Pulmón de Células no Pequeñas , Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Epigenoma , Detección Precoz del Cáncer , ADN de Neoplasias/genética , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/genética , Metilación de ADN/genéticaRESUMEN
1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.
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BACKGROUND: The polygenic risk score (PRS) developed for coronary artery disease (CAD) is known to be effective for classifying patients with CAD and predicting subsequent events. However, the PRS was developed mainly based on the analysis of Caucasian genomes and has not been validated for East Asians. We aimed to evaluate the PRS in the genomes of Korean early-onset AMI patients (n = 265, age ≤50 years) following PCI and controls (n = 636) to examine whether the PRS improves risk prediction beyond conventional risk factors. RESULTS: The odds ratio of the PRS was 1.83 (95% confidence interval [CI]: 1.69-1.99) for early-onset AMI patients compared with the controls. For the classification of patients, the area under the curve (AUC) for the combined model with the six conventional risk factors (diabetes mellitus, family history of CAD, hypertension, body mass index, hypercholesterolemia, and current smoking) and PRS was 0.92 (95% CI: 0.90-0.94) while that for the six conventional risk factors was 0.91 (95% CI: 0.85-0.93). Although the AUC for PRS alone was 0.65 (95% CI: 0.61-0.69), adding the PRS to the six conventional risk factors significantly improved the accuracy of the prediction model (P = 0.015). Patients with the upper 50% of PRS showed a higher frequency of repeat revascularization (hazard ratio = 2.19, 95% CI: 1.47-3.26) than the others. CONCLUSIONS: The PRS using 265 early-onset AMI genomes showed improvement in the identification of patients in the Korean population and showed potential for genomic screening in early life to complement conventional risk prediction.
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Genoma Humano/genética , Infarto del Miocardio/genética , Infarto del Miocardio/terapia , Adulto , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Modelos de Riesgos Proporcionales , República de Corea , Factores de RiesgoRESUMEN
In this study, we developed a semi-active method to run a graphite calorimeter in the quasi-isothermal mode under high-energy x-ray beams. The rate of energy imparted by the beam during irradiation was compensated mainly by removing the electrical heating power based on the pre-calculation and in part by an active automated algorithm, as well, while the temperature of the calorimeter core was kept constant. Irradiations were performed under the linear electron accelerator x-ray beams at 6, 8, 10, 15, and 18 MV. A simple model was applied to analyze the results. The energy imparted to the core was determined with an uncertainty level of 0.2%-0.3%, and the results were reaffirmed by comparing it with that obtained by the quasi-adiabatic mode. The normalized root-mean-square deviation to the mean from the quasi-adiabatic mode was 0.11%, and the associated uncertainty was 0.16% taking into account the correlation of the uncertainty components. This level of agreement showed that the present method is practical for the high-energy x-ray dosimetry.
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Algoritmos , Calorimetría/instrumentación , Calorimetría/métodos , Grafito/química , Aceleradores de Partículas/instrumentación , Temperatura , Incertidumbre , Rayos XRESUMEN
We present the initial phase of the Korean Genome Project (Korea1K), including 1094 whole genomes (sequenced at an average depth of 31×), along with data of 79 quantitative clinical traits. We identified 39 million single-nucleotide variants and indels of which half were singleton or doubleton and detected Korean-specific patterns based on several types of genomic variations. A genome-wide association study illustrated the power of whole-genome sequences for analyzing clinical traits, identifying nine more significant candidate alleles than previously reported from the same linkage disequilibrium blocks. Also, Korea1K, as a reference, showed better imputation accuracy for Koreans than the 1KGP panel. As proof of utility, germline variants in cancer samples could be filtered out more effectively when the Korea1K variome was used as a panel of normals compared to non-Korean variome sets. Overall, this study shows that Korea1K can be a useful genotypic and phenotypic resource for clinical and ethnogenetic studies.
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Genoma Humano , Estudio de Asociación del Genoma Completo , Pueblo Asiatico , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , República de CoreaRESUMEN
PURPOSE: The complex beam delivery techniques for patient treatment using a clinical linear accelerator (linac) may result in variations in the photon spectra, which can lead to dosimetric differences in patients that cannot be accounted for by current treatment planning systems (TPSs). Therefore, precise knowledge of the fluence and energy spectrum (ES) of the therapeutic beam is very important. However, owing to the high energy and flux of the beam, the ES cannot be measured directly, and validation of the spectrum modeled in the TPS is difficult. The aim of this study is to develop an efficient beam transmission measurement procedure for accurately reconstructing the ES of a therapeutic x-ray beam generated by a clinical linac. METHODS: The attenuation of a 6 MV photon beam from an Elekta Synergy Platform clinical linac through different thicknesses of graphite and lead was measured using an ion chamber. The response of the ion chamber as a function of photon energy was obtained using the Monte Carlo (MC) method in the Geant4 simulation code. Using the curves obtained in the photon beam transmission measurements and the ion chamber energy response, the ES was reconstructed using an iterative algorithm based on a mathematical model of the spectrum. To evaluate the accuracy of the spectrum reconstruction method, the reconstructed ES (ESrecon ) was compared to that determined by the MC simulation (ESMC ). RESULTS: The ion chamber model in the Geant4 simulation was well validated by comparing the ion chamber perturbation factors determined by the TRS-398 calibration protocol and EGSnrc; the differences were within 0.57%. The number of transmission measurements was optimized to 10 for efficient spectrum reconstruction according to the rate of increase in the spectrum reconstruction accuracy. The distribution of ESrecon obtained using the measured transmission curves was clearly similar to the reference, ESMC , and the dose distributions in water calculated using ESrecon and ESMC were similar within a 2% local difference. However, in a heterogeneous medium, the dose discrepancy between them was >5% when a complex beam delivery technique composed of 171 control points was used. CONCLUSIONS: The proposed measurement procedure required a total time of approximately 1 h to obtain and analyze 20 transmission measurements. In addition, it was confirmed that the transmission curve of high-Z materials influences the accuracy of spectrum reconstruction more than that of low-Z materials. A well-designed transmission measurement protocol suitable for clinical environments could be an essential tool for better dosimetric accuracy in patient treatment and for periodic verification of the beam quality.
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Aceleradores de Partículas , Fotones , Fenómenos Físicos , Algoritmos , Modelos Teóricos , RadiometríaRESUMEN
Metabolic labeling is one of the most powerful methods to label the live cell for in vitro and in vivo tracking. However, the cellular mechanisms by modified glycosylation due to metabolic agents are not fully understood. Therefore, metabolic labeling has not yet been widely used in EPC tracking and labeling. In this study, cell functional properties such as proliferation, migration and permeability and gene expression patterns of metabolic labeling agent-treated hUCB-EPCs were analyzed to demonstrate cellular effects of metabolic labeling agents. As the results, 10 µM Ac4ManNAz treatment had no effects on cellular function or gene regulations, however, higher concentration of Ac4ManNAz (>20 µM) led to the inhibition of functional properties (proliferation rate, viability and rate of endocytosis) and down-regulation of genes related to cell adhesion, PI3K/AKT, FGF and EGFR signaling pathways. Interestingly, the new blood vessel formation and angiogenic potential of hUCB-EPCs were not affected by Ac4ManNAz concentration. Based on our results, we suggest 10 µM as the optimal concentration of Ac4ManNAz for in vivo hUCB-EPC labeling and tracking. Additionally, we expect that our approach can be used for understanding the efficacy and safety of stem cell-based therapy in vivo.
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Azidas/metabolismo , Rastreo Celular/métodos , Células Progenitoras Endoteliales/efectos de los fármacos , Células Progenitoras Endoteliales/metabolismo , Hexosaminas/metabolismo , Coloración y Etiquetado/métodos , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Endocitosis/efectos de los fármacos , Humanos , Transcriptoma/efectos de los fármacosRESUMEN
We explored whether a mechanically-assisted squat exercise improved muscle mass, muscle function, and pulmonary function in elderly women with or without sarcopenia. In total, 76 community-dwelling elderly subjects (>60 years of age) were screened. We ultimately included 30 subjects who completed more than 80% of the six-week course of mechanically-assisted squat exercises (three days per week, 30 min per day). We measured body composition, lung function, knee extensor strength, hand grip strength, and the 3-min walk distance (3MWD) before and after the exercise program. Subjects with sarcopenia had poor hand grip strength and knee extensor strength, and a slow walking speed. Their lung function parameters, including forced vital capacity (FVC), was lower than those of the controls. After six weeks of squat exercises, the hand grip strength, knee extensor strength, and 3MWD increased significantly in both groups. Appendicular skeletal muscle mass and leg lean mass were increased in subjects without sarcopenia. The FVC (L) increased significantly only in the sarcopenia group (p = 0.019). The mechanically-assisted squat exercise program increased muscle function and lung function, including FVC, in patients with sarcopenia. Muscle mass increased in subjects without sarcopenia.
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BACKGROUND: Asians have among the highest incidence of type 2 diabetes (T2DM) in the world, partly due to low ß-cell function, causing them to rapidly develop T2DM when insulin resistant. This study tested the hypothesis that genetic polymorphisms are responsible for the low ß-cell function and that dietary factors interact with the genes to exacerbate their risk of T2DM. METHODS: We selected 10 genetic variants of 5 genes involved in insulin secretion (CDKAL1, KCNQ1, IDE, HHEX, and ABCA1) from the genome-wide association studies to calculate the genetic risk scores (GRSs) in 8842 Korean adults in the Ansan/Ansung cohort in the Korean Genome Epidemiology Study. The genetic risk score were divided into low, medium, and high groups, and the association between T2DM and the genetic risk score was measured using logistic regression. We also analysed the interaction between the genetic risk score and the nutrition intakes. RESULTS: The individual genetic variants were positively associated with T2DM even when adjusted for covariates. Individuals with medium and high genetic risk score had higher T2DM risk by 1.68 and 2.17 folds compared to those with the low genetic risk score after adjusting for covariates. The increased risk was mainly associated with lower HOMA-B, an indicator of insulin secretion capacity, but not HOMA-IR, an indicator of insulin resistance. Subjects with high carbohydrate intakes and a medium genetic risk score did not have a higher risk of T2DM, and the risk was partially mitigated in the high genetic risk score group. CONCLUSION: Seventy-two percent of the Korean population had either medium or high genetic risk scores for impaired insulin secretion, which approximately doubled their risk of type 2 diabetes, and the risk was exacerbated by consuming a low carbohydrate Western-style diets.
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Pueblo Asiatico/genética , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Dieta/efectos adversos , Predisposición Genética a la Enfermedad , Insulina/metabolismo , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Biomarcadores/análisis , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Incidencia , Resistencia a la Insulina , Secreción de Insulina , Masculino , Persona de Mediana Edad , Pronóstico , República de Corea/epidemiología , Factores de RiesgoRESUMEN
This study was undertaken to develop and cross-validate reference and individual predictive models for estimating functional thigh muscle cross-sectional area (TCSA) by 2-point Dixon magnetic resonance imaging (MRI). TCSAs of dominant sides at the mid-thigh level were measured by 2-point Dixon MRI (MRITCSA). Functional MRITCSA were compared with the predictive models in a sample of 92 younger (20-40 years; 28.55±4.87; n=50) and older (>65years; 71.22±4.82; n=42) Koreans. Lean body masses were measured by dual energy X-ray absorptiometry (DXALBM), and thigh isokinetic muscle strengths, extension peak torque at 60°/sec, were measured using a Biodex® dynamometer (BiodexEPT). Multiple regression analysis generated the reference model (R2=0.75 and SEE=1472.63mm2 (8%)) as follows: The reference model: functional TCSA(mm2)=-1230.49+62.81*height+3061.78*gender -2692.57*age+58.91*weight. The individual model (R2=0.80, SEE=1158.34mm2 (7%)) was as follows: The individual model: functional TCSA(mm2)=1631.62+1.76* DXALBM+9.51*BiodexEPT where height is in centimeters; weight is in kilograms; for gender, female=0 and male=1; and for age, age under 40=1 and age over 65=2. PRESS statistics of R2 and SEE were 0.78 and 1382.98mm2 for the reference model, and 0.88 and 979.02mm2 for the individual model. The 2-point Dixon MRI appears to be valid for measuring functional muscle size. Our results suggest that the reference and individual models provide acceptable estimates of functional thigh muscle CSA in healthy Korean adults. Therefore, the models developed in the study could be useful as a research tool to establish indexes for functional muscle composition in healthy Koreans.
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Imagen por Resonancia Magnética/métodos , Músculo Cuádriceps/anatomía & histología , Adulto , Anciano , Peso Corporal , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Tamaño de los Órganos , Valor Predictivo de las Pruebas , Músculo Cuádriceps/fisiología , República de Corea , Adulto JovenRESUMEN
Many studies of the toxic effects of zinc oxide nanoparticles (ZnO NPs) in aquatic organisms have been performed because of increasing ZnO NP use. However, the toxicological pathways are not understood. In this study, ZnO NPs were found to be more toxic than ZnSO4 to zebrafish larvae, but ZnO NP toxicity did not involve transcript alterations. Biological processes affected by ZnO NPs and ZnSO4 were investigated by performing ingenuity pathway analysis on differently expressed genes in larvae exposed to sub-lethal ZnO NP and ZnSO4 concentrations. We identified upregulated and downregulated differently expressed genes in fish exposed to ZnO NPs and ZnSO4, and found that ZnO NPs slightly induced cell differentiation and pathways associated with the immune system and activated several key genes involved in cancer cell signaling. The results may be key to predicting and elucidating the mechanisms involved in ZnO NP and ZnSO4 toxicity in zebrafish larvae.
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Nanopartículas/toxicidad , Pez Cebra/genética , Óxido de Zinc/toxicidad , Sulfato de Zinc/toxicidad , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Exposición a Riesgos Ambientales , Regulación de la Expresión Génica/efectos de los fármacos , Larva/efectos de los fármacos , Larva/genética , Transducción de Señal/efectos de los fármacosRESUMEN
DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next-generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short-term calorie restriction (CR) on the methylome of aged rat kidney. Whole-genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4-week, short-term CR) rats was analyzed by methylated DNA immunoprecipitation and next-generation sequencing (MeDIP-Seq). CpG islands and repetitive regions were hypomethylated, but 5'-UTR, exon, and 3'-UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short-term CR could partially ameliorate age-related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease-related genes during aging may indicate increases in susceptibility to age-related diseases. Therefore, the CR-induced epigenetic changes that ameliorate age-dependent aberrant methylation may be important to CR's health- and life-prolonging effects.
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Current evidence indicates that there is a relationship between microRNA (miRNA)-mediated gene silencing and low-dose irradiation (LDIR) responses. Here, alterations of miRNA expression in response to LDIR exposure in male BALB/c mice and three different types of hepatocytes were investigated. The miRNome of the LDIR-exposed mouse spleens (0.01 Gy, 6.5 mGy/h) was analyzed, and the expression of miRNA and mRNA was validated by qRT-PCR. Western blotting, chromatin immunoprecipitation (ChIP), and luciferase assays were also performed to evaluate the interaction between miRNAs and their target genes and to gain insight into the regulation of miRNA expression. The expression of miRNA-193b-3p was down-regulated in the mouse spleen and liver and in various hepatocytes (NCTC, Hepa, and HepG2 cell lines) in response to LDIR. The down-regulation of miR-193b-3p expression was caused by histone deacetylation on the miR-193b-3p promoter in the HepG2 cells irradiated with 0.01 Gy. However, the alteration of histone deacetylation and miR-193b-3p and Rad51 expression in response to LDIR was restored by pretreatment with N-acetyl-cyctein. In conclusion, we provide evidence that miRNA responses to LDIR include the modulation of cellular stress responses and repair mechanisms.
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Regulación hacia Abajo/efectos de la radiación , Regulación de la Expresión Génica/efectos de la radiación , Hepatocitos/efectos de la radiación , MicroARNs/genética , Recombinasa Rad51/genética , Animales , Línea Celular , Línea Celular Tumoral , Daño del ADN , Relación Dosis-Respuesta en la Radiación , Perfilación de la Expresión Génica/métodos , Células HCT116 , Células Hep G2 , Hepatocitos/metabolismo , Humanos , Masculino , Ratones Endogámicos BALB C , Recombinasa Rad51/metabolismoRESUMEN
Age-related dysregulated inflammation plays an essential role as a major risk factor underlying the pathophysiological aging process. To better understand how inflammatory processes are related to aging at the molecular level, we sequenced the transcriptome of young and aged rat kidney using RNA-Seq to detect known genes, novel genes, and alternative splicing events that are differentially expressed. By comparing young (6 months of age) and old (25 months of age) rats, we detected 722 up-regulated genes and 111 down-regulated genes. In the aged rats, we found 32 novel genes and 107 alternatively spliced genes. Notably, 6.6% of the up-regulated genes were related to inflammation (P < 2.2 × 10-16, Fisher exact t-test); 15.6% were novel genes with functional protein domains (P = 1.4 × 10-5); and 6.5% were genes showing alternative splicing events (P = 3.3 × 10-4). Based on the results of pathway analysis, we detected the involvement of inflammation-related pathways such as cytokines (P = 4.4 × 10-16), which were found up-regulated in the aged rats. Furthermore, an up-regulated inflammatory gene analysis identified the involvement of transcription factors, such as STAT4, EGR1, and FOSL1, which regulate cancer as well as inflammation in aging processes. Thus, RNA changes in these pathways support their involvement in the pro-inflammatory status during aging. We propose that whole RNA-Seq is a useful tool to identify novel genes and alternative splicing events by documenting broadly implicated inflammation-related genes involved in aging processes.
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Envejecimiento/metabolismo , Empalme Alternativo , Inflamación/metabolismo , Transducción de Señal/genética , Envejecimiento/genética , Envejecimiento/patología , Animales , Biomarcadores/metabolismo , Regulación hacia Abajo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Estudios de Factibilidad , Perfilación de la Expresión Génica , Inflamación/genética , Riñón/metabolismo , Riñón/patología , Masculino , Proteínas Proto-Oncogénicas c-fos/metabolismo , ARN/genética , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT4/metabolismo , Análisis de Secuencia de ARN , Organismos Libres de Patógenos Específicos , Transcriptoma , Regulación hacia ArribaRESUMEN
This study investigated the degree to which instrumental measurements explain the variation in pork loin tenderness as assessed by the sensory evaluation of trained panelists. Warner-Bratzler shear force (WBS) had a significant relationship with the sensory tenderness variables, such as softness, initial tenderness, chewiness, and rate of breakdown. In a regression analysis, WBS could account variations in these sensory variables, though only to a limited proportion of variation. On the other hand, three parameters from texture profile analysis (TPA)-hardness, gumminess, and chewiness-were significantly correlated with all sensory evaluation variables. In particular, from the result of stepwise regression analysis, TPA hardness alone explained over 15% of variation in all sensory evaluation variables, with the exception of perceptible residue. Based on these results, TPA analysis was found to be better than WBS measurement, with the TPA parameter hardness likely to prove particularly useful, in terms of predicting pork loin tenderness as rated by trained panelists. However, sensory evaluation should be conducted to investigate practical pork tenderness perceived by consumer, because both instrumental measurements could explain only a small portion (less than 20%) of the variability in sensory evaluation.
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A quartz crystal microbalance (QCM) was utilized to measure the water content in ethanol. For the improvement of measurement sensitivity, the QCM was modified by applying zeolite particles on the surface with poly(methyl methacrylate) (PMMA) binder. The measurement performance was examined with ethanol of 1% to 5% water content in circulation. The experimental results showed that the frequency drop of the QCM was related with the water content though there was some deviation. The sensitivity of the zeolite-coated QCM was sufficient to be implemented in water content determination, and a higher ratio of silicon to aluminum in the molecular structure of the zeolite gave better performance. The coated surface was inspected by microscopy to show the distribution of zeolite particles and PMMA spread.