• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.451-460
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• 2015

Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7049-7052
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• 2015

Background: Helicobacter pylori plays an important role in gastric cancer, which has a relatively low inciduence in Thailand. MDM2 is a major negative regulator of p53, the key tumor suppressor involved in tumorigenesis of the majority of human cancers. Whether its expression might explain the relative lack of gastric cancer in Thailand was assessed here. Materials and Methods: This single-center study was conducted in the northeast region of Thailand. Gastric mucosa from 100 patients with Helicobacter pylori associated gastritis was analyzed for MDM2 SNP309 using real-time PCR hybridization (light-cycler) probes. Results: In the total 100 Helicobacter pylori associated gastritis cases the incidence of SNP 309 T/T homozygous was 78 % with SNP309 G/T heterozygous found in 19% and SNP309 G/G homozygous in 3%. The result show SNP 309 T/T and SNP 309 G/T to be rather common in the Thai population. Conclusions: Our study indicates that the MDM2 SNP309 G/G homozygous genotype might be a risk factor for gastric cancer in Thailand and the fact that it is infrequent could explain to some extent the low incidence of gastric cancer in the Thai population.

• Tuberculosis and Respiratory Diseases
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• 제62권3호
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• pp.211-216
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• 2007

저자들은 평소 건강하게 지내던62세 남자 환자에게서 발생한 우하지 심부정맥혈전증과 폐색전증의 원인으로 과호모시스테인혈증이 독립적인 위험인자로 작용한 것으로 생각되는 1예를 경험하였기에 문헌고찰과 함께 보고한다.

• 생태와환경
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• 제52권4호
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• pp.394-402
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• 2019

The Agrobacterium tumefaciens mediated gene transfer is widely used to generate genetic transformation of plants and transient assay of temporal exogenous gene expression. Syringe infiltration system into tobacco (Nicotiana benthamiana) leaves is a powerful tool for transient expression of target protein to study protein localization, protein-protein binding and protein production. However, the protocol and technical information of transient gene expression, especially double strand RNA (dsRNA), in tobacco using Agrobacterium is not well known. Recently, dsRNA is crucial for insecticidal effect on destructive agronomic pest such as Corn rootworm. In this study, we investigated the factor influencing the dsRNA expression efficiency of syringe agro-infiltration in tobacco. To search the best combination for dsRNA transient expression in tobacco, applied two Agrobacterium cell lines and three plant vector systems. The efficiency of dsRNA expression has estimated by real-time PCR and digital PCR. As a result, pHellsgate12 vector constructs showed the most effective accumulation of dsRNA in the cell. These results indicated that the efficiency of dsRNA expression was depending on the kind of vector rather than Agrobacterium cells. In summary, the optimized combination of transient dsRNA expression system in tobacco might be useful to in vivo dsRNA expression for functional study and risk assessment of dsRNA.

• Nutrition Research and Practice
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• 제5권3호
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• pp.253-259
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• 2011

The rapid rise in the incidence of obesity has emerged as one of the most pressing global public health issues in recent years. The underlying etiological causes of obesity, whether behavioral, environmental, genetic, or a combination of several of them, have not been completely elucidated. The obesity epidemic has been attributed to the ready availability, abundance, and overconsumption of high-energy content food. We determined here by Pearson's correlation the relationship between food type consumption and rising obesity using the loss-adjusted food availability data from the United States Department of Agriculture (USDA) Economic Research Services (ERS) as well as the obesity prevalence data from the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health and Nutrition Examination Survey (NHANES) at the Centers for Disease Control and Prevention (CDC). Our analysis showed that total calorie intake and consumption of high fructose com syrup (HFCS) did not correlate with rising obesity trends. Intake of other major food types, including chicken, dairy fats, salad and cooking oils, and cheese also did not correlate with obesity trends. However, our results surprisingly revealed that consumption of com products correlated with rising obesity and was independent of gender and race/ethnicity among population dynamics in the U.S. Therefore, we were able to demonstrate a novel link between the consumption of com products and rising obesity trends that has not been previously attributed to the obesity epidemic. This correlation coincides with the introduction of bioengineered corns into the human food chain, thus raising a new hypothesis that should be tested in molecular and animal models of obesity.

• Tuberculosis and Respiratory Diseases
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• 제47권2호
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• pp.239-246
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• 1999

저자등은 우하지 동통 및 객혈을 주소로 내원하여 우하지 심부정맥혈전증, 폐색전증 및 뇌정맥혈전증으로 환자에서 과호모시틴혈증이 다발성 혈전증의 원인이었던 1예를 경험 하였기에 문헌고찰과 함께 보고하는 바이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7149-7152
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• 2014

A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or $Spi^-$ mutant frequencies between STD- and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations.

• 대한정형도수물리치료학회지
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• 제11권1호
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• pp.65-73
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• 2005

Osteoarthritis has been considered a disease of the elderly because it is uncommon before the age of 40 years and is seen in approximately 80% of United States citizens older than 65 years. general population on kuri city in korea revealed that prevalence of knee osteoarthritis is 10.2%, increasing with age. High level of physical activity in men and age, post-menopause and obesity in women can be risk factor. Osteoarthritis is no evidence that a acquired process initiated much earlier in life through mechanical, metabolic, genetic, or other origins. A high tibial osteotomy alters static lower extremity alignment thereby decreasing medial compartment loading. As well, conservative treatment strategies, such as knee braces and valgus heel wedges, affect lover limb mechanics and attempt to reduce medial compartment loading. It was hypothesized that valgus heel wedges and modified orthoses would shift the center of pressure laterally on the foot during level walking, reducing the moment arm of the adduction moment in the frontal plane, thereby resulting in a decrease in the knee adduction moment. In the 1980s, the effect of wearing a laterally wedged insole on osteoarthritic patients with a varus deformity of the knee was firsted, and since then, kinematic and kinetic analyses concerning this condition have mainly focused on a static standing position. Since the early 1990s, the beneficial effect of wearing a laterally wedged insole to treat osteoarthritis of the knee has also been reported in dynamic conditions, but these studies did not answer the question of the kinematic and kinetic mechanisms that resulted in the reduced symptoms in patents with knee osteoarthritis. therefore, the effect of wearing laterally wedged insole has not been sufficiently studied.

• Molecules and Cells
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• 제46권7호
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

• Genomics & Informatics
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• 제9권2호
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• pp.52-58
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• 2011

Osteoporotic fracture (OF), along with bone mineral density (BMD), is an important diagnostic parameter and a clinical predictive risk factor in the assessment of osteoporosis in the elderly population. However, a genome-wide association study (GWAS) on OF has not yet been clarified sufficiently. To identify OF-associated genetic variants and candidate genes, we conducted a GWAS in a population-based cohort (Korean Association Resource [KARE], n=1,427 [case: 288 and control: 1139]) and performed a de novo replication study in hospital-based individuals (Asan and Catholic Medical Center [ACMC], n=1,082 [case: 272 and control: 810]). In a combined meta-analysis, a newly identified genetic locus in an intergenic region at 10p11.2 (near genes FZD8 and ANKRD30A ) showed the most significant association (odd ratio [OR] = 2.00, 95% confidence interval [CI] = 1.47~2.74, p=$1.27{\times}10^{-6}$) in the same direction. We provide the first evidence for a common genetic variant influencing OF and genetic information for further investigation in bone metabolism.