• Genes and Genomics
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• 제40권11호
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• pp.1149-1155
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• 2018

Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.

• International Neurourology Journal
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• 제22권4호
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• pp.268-274
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• 2018

Purpose: To describe a technique for urodynamic diagnosis of detrusor sphincter dyssynergia (DSD) using urethral pressure measurements and examine potential associations between urethral pressure and bladder physiology among patients with DSD. Methods: Multiple sclerosis (MS) and spinal cord injured (SCI) patients with known DSD diagnosed on videourodynamics (via electromyography or voiding cystourethrography) were retrospectively identified. Data from SCI and MS patients with detrusor overactivity (DO) without DSD were abstracted as control group. Urodynamics tracings were reviewed and urethral pressure DSD was defined based on comparison of DSD and control groups. Results: Seventy-two patients with DSD were identified. Sixty-two (86%) had >20 cm $H_2O$ urethral pressure amplitude during detrusor contraction. By comparison, 5 of 23 (22%) of control group had amplitude of >20 cm $H_2O$ during episode of DO. Mean duration of urethral pressure DSD episode was 66 seconds (range, 10-500 seconds) and mean urethral pressure amplitude was 73 cm $H_2O$ (range, 1-256 cm $H_2O$). Longer (>30 seconds) DSD episodes were significantly associated with male sex (81% vs. 50%, P=0.013) and higher bladder capacity (389 mL vs. 219 mL, P=0.0004). Urethral pressure amplitude measurements during DSD were not associated with significant urodynamic variables or neurologic pathology. Conclusions: Urethral pressure amplitude of >20 cm $H_2O$ during detrusor contraction occurred in 86% of patients with known DSD. Longer DSD episodes were associated with larger bladder capacity. Further studies exploring the relationship between urethral pressure measurements and bladder physiology could phenotype DSD as a measurable variable rather than a categorical observation.

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.283-289
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• 2019

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence- associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity. Tenovin-1-treated astrocytes showed increased SA-${\beta}$-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-$1{\beta}$, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.

• 농업과학연구
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• 제45권4호
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• pp.707-713
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• 2018

This study was done to search for positional candidate genes associated with the back fat thickness trait using a Genome-Wide Association Study (GWAS) in purebred Yorkshires (N = 1755). Genotype and phenotype analyses were done for 1,642 samples. As a result of the associations with back fat thickness using the Gemma program (ver. 0.93), when the genome-wide suggestive threshold was determined using the Bonferroni method ($p=1.61{\times}10^{-5}$), the single nucleotide polymorphism (SNP) markers with suggestive significance were identified in 1 SNP marker on chromosome 2 (MARC0053928; $p=3.65{\times}10^{-6}$), 2 SNP markers on chromosome 14 (ALGA0083078; $p=7.85{\times}10^{-6}$, INRA0048453; $p=1.27{\times}10^{-5}$), and 1 SNP marker on chromosome 18 (ALGA0120564; $p=1.44{\times}10^{-5}$). We could select positional candidate genes (KCNQ1, DOCK1, LOC106506151, and LOC110257583), located close to the SNP markers. Among these, we identified a potassium voltage-gated channel subfamily Q member gene (KCNQ1) and the dedicator of cytokinesis 1 (DOCK1) gene associated with obesity and Type-2 diabetes. The SNPs and haplotypes of the KCNQ1 and DOCK1 genes can contribute to understanding the genetic structure of back fat thickness. Additionally, it may provide basic data regarding marker assisted selection for a meat quality trait in pigs.

• 식품보건융합연구
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• 제5권3호
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• pp.1-5
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• 2019

The field experiment was conducted in vegetable area, Institute of Horticultural Sciences in University of Agriculture, Faisalabad in order to recognize morphological and fruit growth pattern and yield of Tinda (Praecitrullus fistulosus) gourd germplasm lines. Sixteen germplasm lines in which one line is used as check are included were sown and grown on flat beds in field. The field experiment was arranged as randomized complete block design (RCBD) with three replications. Data on days to maturity, fruit per vine, fruit weight in grams, fruit diameter and total yield obtained were recorded. The fruit texture is marked as phenotype parameter. All parameters were collected and then analyzed statistically. All lines and replications showed different results among each other according to parameter. The maximum DTM (days to maturity), F/P (fruit per plant), FW (fruit weight), FD (fruit diameter) and Yield were recorded was $L_0$ (68.66), $L_3$ (1.66), $L_{10}$ (248.33), $L_{13}$ (8.50) and $L_0$ (599.33) and the minimum were recorded was $L_1$ (56), $L_{11}$ (0.33), $L_0$ (198), $L_9$ (7) and $L_4$ (421) grams respectively. All lines showed smooth texture of fruits with no hairs when mature at harvesting stage.

• Journal of Sleep Medicine
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• 제15권2호
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• pp.48-54
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• 2018

Objectives: The aim of this study was to develop a predicting model for the optimal continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) patient with obesity by using a machine learning. Methods: We retrospectively investigated the medical records of 162 OSA patients who had obesity [body mass index (BMI) ≥ 25] and undertaken successful CPAP titration study. We divided the data to a training set (90%) and a test set (10%), randomly. We made a random forest model and a least absolute shrinkage and selection operator (lasso) regression model to predict the optimal pressure by using the training set, and then applied our models and previous reported equations to the test set. To compare the fitness of each models, we used a correlation coefficient (CC) and a mean absolute error (MAE). Results: The random forest model showed the best performance {CC 0.78 [95% confidence interval (CI) 0.43-0.93], MAE 1.20}. The lasso regression model also showed the improved result [CC 0.78 (95% CI 0.42-0.93), MAE 1.26] compared to the Hoffstein equation [CC 0.68 (95% CI 0.23-0.89), MAE 1.34] and the Choi's equation [CC 0.72 (95% CI 0.30-0.90), MAE 1.40]. Conclusions: Our random forest model and lasso model ($26.213+0.084{\times}BMI+0.004{\times}$apnea-hypopnea index+$0.004{\times}oxygen$ desaturation index-$0.215{\times}mean$ oxygen saturation) showed the improved performance compared to the previous reported equations. The further study for other subgroup or phenotype of OSA is required.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.139-146
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• 2021

Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) produces NADPH, which is known to inhibit mitochondrial oxidative stress. Ureteral obstruction induces kidney inflammation and fibrosis via oxidative stress. Here, we investigated the role and underlying mechanism of IDH2 in unilateral ureteral obstruction (UUO)-induced kidney inflammation using IDH2 gene deleted mice (IDH2-/-). Eight- to 10-week-old female IDH2-/- mice and wild type (IDH2+/+) littermates were subjected to UUO and kidneys were harvested 5 days after UUO. IDH2 was not detected in the kidneys of IDH2-/- mice, while UUO decreased IDH2 in IDH2+/+ mice. UUO increased the expressions of markers of oxidative stress in both IDH2+/+ and IDH2-/- mice, and these changes were greater in IDH2-/- mice compared to IDH2+/+ mice. Bone marrow-derived macrophages of IDH2-/- mice showed a more migrating phenotype with greater ruffle formation and Rac1 distribution than that of IDH2+/+ mice. Correspondently, UUO-induced infiltration of monocytes/macrophages was greater in IDH2-/- mice compared to IDH2+/+ mice. Taken together, these data demonstrate that IDH2 plays a protective role against UUO-induced inflammation through inhibition of oxidative stress and macrophage infiltration.

• 전기전자학회논문지
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• 제26권3호
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• pp.494-499
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• 2022

본 논문에서는 인간의 피부섬유모세포(Human dermal fibroblasts)로부터 확보한 전사체 정보를 활용하여 나이를 예측하는 방법을 소개한다. 제안 방법에서는 훈련을 통해 확보한 분류기 및 회귀 모델을 이용하여 샘플이 속한 적합한 연령 그룹을 선택한 후, 선택된 연령 그룹에 속하는 훈련 데이터의 관측값을 활용하여 구체적인 연령을 예측한다. 연령을 예측하려는 샘플이 입력되면 복수 개의 판별 규칙이 순서대로 실행되는데, 개별 판별 규칙에서는 분류기와 회귀 모델을 동시에 실행하여 해당 판별 규칙에 대한 선택조건이 만족되는지 여부를 확인한다. 선택 조건이 만족될 경우 판별 규칙의 타겟 연령 그룹에 속하는 데이터를 이용하여 훈련된 회귀 모델로 연령을 예측하며, 선택 조건이 만족되지 않으면 후속 판별 규칙을 실행한다. 공개 데이터에 대하여 실험한 결과 기존 연구에서 달성한 7.7년의 평균 예측 오차보다 우수한 5.7년이라는 평균 예측 오차를 달성함을 확인하였다.

• Journal of Microbiology and Biotechnology
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• 제31권8호
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• pp.1098-1108
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• 2021

The literature indicates that LINC00174 promotes the growth of colorectal cancer (CRC) cells, but its research needs to be enriched. We tried to explore the function and mechanism of LINC00174 in CRC cell proliferation and migration. Bioinformatics analysis predicted the binding relationship and expressions of lncRNA, miRNA and mRNA. Clinical study analyzes the relationship between LINC00174 and clinical data characteristics of CRC patients. The expressions of LINC00174, miR-3127-5p and E2F7 were verified by RT-qPCR, and the combination of the two was verified by dual luciferase analysis and RNA immunoprecipitation as needed. Western blot was used to detect the expression of EMT-related protein and E2F7 protein. Functional experiments were used to evaluate the function of the target gene on CRC cells. LINC00174 was up-regulated in CRC clinical samples and cells and was related to the clinical characteristics of CRC patients. High-expression of LINC00174, contrary to the effect of siLINC00174, promoted cell viability, proliferation, migration and invasion, up-regulated the expressions of N-Cadherin, Vimentin, E2F7, and inhibited the expression of E-Cadherin. MiR-3127-5p was one of the targeted miRNAs of LINC00174 and was down-regulated in CRC samples. In addition, miR-3127-5p mimic partially reversed the malignant phenotype of CRC cells induced by LINC00174. Besides, E2F7 was a target gene of miR-3127-5p, and LINC00174 repressed miR-3127-5p to regulate E2F7. Our research reveals that LINC00174 affected the biological characteristics of CRC cells through regulated miR-3127-5p/ E2F7 axis.

• Journal of Nutrition and Health
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• 제55권6호
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• pp.601-616
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• 2022

In the era of the fourth industrial revolution technology, the inclusion of personalized nutrition for healthcare (PNH), when establishing a healthcare platform to prevent chronic diseases such as obesity, diabetes, cerebrovascular and cardiovascular disease, pulmonary disease, and inflammatory diseases, enhances the national competitiveness of global healthcare markets. Furthermore, since the government experienced COVID-19 and the population dead cross in 2020, as well as numerous health problems due to an increasing super-aged Korean society, there is an urgent need to secure, develop, and utilize PNH-related technologies. Three conditions are essential for the development of PNH technologies. These include the establishment of causality between obesity genome (genotype) and prevalence (phenotype) in Koreans, validation of clinical intervention research, and securing PNH-utilization technology (i.e., algorithm development, artificial intelligence-based platform, direct-to-customer [DTC]-based PNH, etc.). Therefore, a national control tower is required to establish appropriate PNH infrastructure (basic and clinical research, cultivation of PNH-related experts, etc.). The post-corona era will be aggressive in sharing data knowledge and developing related technologies, and Korea needs to actively participate in the large-scale global healthcare markets. This review provides the importance of scientific evidence based on a huge dataset, which is the primary prerequisite for the DTC obesity gene-based PNH technologies to be competitive in the healthcare market. Furthermore, based on comparing domestic and internationally approved DTC obese genes and the current status of Korean obesity genome-based PNH research, we intend to provide a direction to PNH planners (individuals and industries) for establishing scientific PNH guidelines for the prevention of obesity.