• BMB Reports
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• 제56권3호
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• pp.196-201
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• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• 전자공학회논문지CI
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• 제46권6호
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• pp.7-17
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• 2009

효과적인 재활 시스템을 구상하는데 있어서 훈련 데이터의 정교한 분석은 다음 단계 훈련을 위한 피드백 자료로서 매우 중요하다. 현재 다양한 생체 역학적 실험을 통해 인간의 운동 능력을 평가하고 이로부터 생성된 데이터의 분석을 위한 객관적이고 신뢰성 있는 연구결과들이 발표되고 있다. 그러나 대부분의 기존 연구들은 기초 통계적인 방법에 근거한 정량분석만을 수행함으로써, 획득된 정보를 임상에 적용 하는데 있어서는 충분한 신뢰성을 보장할 수 없다. 데이터마이닝은 대용량 데이터에 들어있는 숨겨진 규칙과 패턴을 탐사함으로써 임상 데이터에 숨어있는 의미 있는 정보추출에 성공적으로 사용되고 있으며, 특히 임상 연구 분야에서는 훌륭한 의사 결정 지원 시스템으로서 점점 그 사용이 증가되고 있다. 본 연구에서는 신뢰성 있는 자세 제어 능력(Postural control ability) 평가를 위해서 측정된 훈련 데이터에 가중연관규칙 탐사를 적용하여 자세 훈련 유형에 따른 근육 활성 패턴과의 연관성을 분석, 효율적인 재활 훈련 규칙을 탐사하였다. 탐사된 규칙은 재활 및 임상 전문가의 의사결정에 더욱 정성적이고 유용한 선험적 지식으로 사용 될 수 있으며, 이를 근거로 환자 맞춤형 최적의 재활 훈련 모델을 구상하기 위한 지표로서 사용될 수 있다.

• Molecules and Cells
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• 제38권12호
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• pp.1037-1043
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• 2015

The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

• BMB Reports
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• 제57권2호
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• pp.116-121
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• 2024

We investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell-conditioned medium (BMSC-CM) on immortalized renal proximal tubule epithelial cells (RPTEC/TERT1) in a fibrotic environment. To replicate the increased stiffness characteristic of kidneys in chronic kidney disease, we utilized polyacrylamide gel platforms. A stiff matrix was shown to increase α-smooth muscle actin (α-SMA) levels, indicating fibrogenic activation in RPTEC/TERT1 cells. Interestingly, treatment with BMSC-CM resulted in significant reductions in the levels of fibrotic markers (α-SMA and vimentin) and increases in the levels of the epithelial marker E-cadherin and aquaporin 7, particularly under stiff conditions. Furthermore, BMSC-CM modified microRNA (miRNA) expression and reduced oxidative stress levels in these cells. Our findings suggest that BMSC-CM can modulate cellular morphology, miRNA expression, and oxidative stress in RPTEC/TERT1 cells, highlighting its therapeutic potential in fibrotic kidney disease.

• 한국운동역학회지
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• 제32권1호
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• pp.17-23
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• 2022

Objective: The aim of this study was to investigate the effect Tiger-step walking on the movement of the lower extremities during walking. Method: Twenty healthy male adults who had no experience of musculoskeletal injuries on lower extremities in the last six months (age: 26.85 ± 3.28 yrs, height: 174.6 ± 3.72 cm, weight: 73.65 ± 7.48 kg) participated in this study. In this study, 7-segments whole-body model (pelvis, both side of thigh, shank and foot) was used and 29 reflective markers and cluster were attached to the body to identify the segments during the gait. A 3-dimensional motion analysis with 8 infrared cameras and 7 channeled EMG was performed to find the effect of tigerstep on uphill walking. To verify the tigerstep effect, a one-way ANOVA with a repeated measure was used and the statistical significance level was set at α=.05. Results: Firstly, Both Tiger-steps showed a significant increase in stance time and stride length compared with normal walking (p<.05), while both Tiger-steps shown significantly reduced cadence compared to normal walking (p<.05). Secondly, both Tiger-steps revealed significantly increased in hip and ankle joint range of motion compared with normal walking at all planes (p<.05). On the other hand, both Tiger-steps showed significantly increased knee joint range of motion compared with normal walking at the frontal and transverse planes (p<.05). Lastly, Gluteus maximus, biceps femoris, medial gastrocnemius, tibialis anterior of both tiger-step revealed significantly increased muscle activation compared with normal walking in gait cycle and stance phase (p<.05). On the other hand, in swing phase, the muscle activity of the vastus medialis, biceps femoris, tibialis anterior of both tiger-step significantly increased compared with those of normal walking (p <.05). Conclusion: As a result of this study, Tiger step revealed increased in 3d range of motion of lower extremity joints as well as the muscle activities associated with range of motion. These findings were evaluated as an increase in stride length, which is essential for efficient walking. Therefore, the finding of this study prove the effectiveness of the tiger step when walking uphill, and it is thought that it will help develop a more efficient tiger step in the future, which has not been scientifically proven.

• 농업과학연구
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• 제47권4호
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• pp.1109-1122
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• 2020

The aim of this study was to develop a marbling classification and prediction model using small parts of sirloin images based on a deep learning algorithm, namely, a convolutional neural network (CNN). Samples were purchased from a commercial slaughterhouse in Korea, images for each grade were acquired, and the total images (n = 500) were assigned according to their grade number: 1++, 1+, 1, and both 2 & 3. The image acquisition system consists of a DSLR camera with a polarization filter to remove diffusive reflectance and two light sources (55 W). To correct the distorted original images, a radial correction algorithm was implemented. Color images of sirloins of Hanwoo (mixed with feeder cattle, steer, and calf) were divided and sub-images with image sizes of 161 × 161 were made to train the marbling prediction model. In this study, the convolutional neural network (CNN) has four convolution layers and yields prediction results in accordance with marbling grades (1++, 1+, 1, and 2&3). Every single layer uses a rectified linear unit (ReLU) function as an activation function and max-pooling is used for extracting the edge between fat and muscle and reducing the variance of the data. Prediction accuracy was measured using an accuracy and kappa coefficient from a confusion matrix. We summed the prediction of sub-images and determined the total average prediction accuracy. Training accuracy was 100% and the test accuracy was 86%, indicating comparably good performance using the CNN. This study provides classification potential for predicting the marbling grade using color images and a convolutional neural network algorithm.

• 대한본초학회지
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• 제30권2호
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• pp.11-18
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• 2015

Objectives : Polygoni Multiflori Radix (Jeokhasuo in Korean) is a Oriental traditional herbs widely used in East Asian countries. Overconsumption of fructose results in hypertension, dyslipidemia, obesity and impaired glucose tolerance which have documented as a risk of cardiovascular diseases. This experimental study was designed to investigate the beneficial effects of an ethanol extract from Polygoni Multiflori Radix (PMR) in high-fructose (HF) diet-induced metabolic syndrome rat model. Methods : Sprague-Dawley (SD) rats were divided into three groups; Control group, receiving regular diet and tap water, HF group, and HF + PMR group both receiving supplemented with 65% fructose (n=10), respectively. The HF + PMR group initially received HF diet with PMR (100 mg/kg/day) for 8 weeks. Results : PMR significantly prevented the metabolic disturbances such as hyperlipidemia, hypertension and impaired glucose tolerance. Chronic treatment with PMR significantly decreased body weight, fat weight and adipocyte size, suggesting a role of anti-obesity effect. PMR led to improve the hyperlipidemia through the increase in HDL cholesterol level as well as the decrease in triglyceride and LDL cholesterol level. In addition, PMR suppressed adhesion molecules and endothelin-1 (ET-1) expression in aorta resulting in the decrease of hypertension. In muscle tissue, PMR significantly recovered the HF-induced insulin resistance through increase of insulin receptor substrate-1 (IRS-1), p-$AMPK{\alpha}1/2$, and p-Akt expression. PMR improved HF-induced metabolic disorders and its action was caused by energy metabolism-mediated insulin signaling activation. Conclusions : These results demonstrate that PMR may be a beneficial therapeutic for metabolic syndrome through the improvement of hyperlipidemia, obesity, insulin resistance and hypertension.

• Biomolecules & Therapeutics
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• 제32권4호
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• pp.432-441
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• 2024

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

• 대한의생명과학회지
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• 제18권3호
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• pp.227-236
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• 2012

Previous study showed that swimming improved obesity but was not through $PPAR{\alpha}$ activation in liver and skeletal muscle in high fat diet-fed female mice with functioning ovaries as an animal model of obese premenopausal women. Thus, this study was aimed at investigation of the effects of swimming on the promotion of health and its molecular mechanism in adipose tissue of high fat diet-fed female mice. Eight-week-old female C57BL/6J mice were randomly divided into two groups (a non-swim control group and a swim group, n=8/group). Mice in the swim group swam for 2 h daily for 6 weeks in water bath with temperature of $35{\pm}1^{\circ}C$. All the animals received high fat diet (45% kcal fat) for 6 weeks. Reverse transcription-polymerase chain reaction was used to elucidate the molecular mechanism. Female mice subjected to swimming had significantly decreased body weight gain and white adipose tissue mass compared with the female control mice. Histological studies illustrated that swimming decreases the hepatic lipid accumulation. As expected, swimming did not affect the expression of mRNA levels of peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation, such as carnitine palmitoyltransgerase-1 and medium chain acyl-CoA dehydrogenase in the white adipose tissue. However, mice that underwent 6-weeks of swimming exercise had decreased the mRNA expression of lipogenic genes, such as sterol regulatory element-binding proteins-1C and fatty acid synthase in comparison to sedentary control mice, with decreased $PPAR{\gamma}$ target genes involved in adipocyte-specific marker genes, such as adipocyte fatty acid binding protein and leptin in the white adipose tissue. These results suggest that swimming can effectively prevent obesity induced by high fat diet-fed, in part through down-regulation of adipogenesis and lipogenesis in white adipose tissue of female obese mice. Moreover, these results suggest that swimming maybe contributing the promotion of health through regulation of adipogenesis and lipogenesis in overweight premenopausal women.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.467-472
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• 2015

Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I ($AT_1R$) inhibitor, valsartan ($10{\mu}M$), but not by the $AT_2R$ inhibitor, PD123319. TSA ($1{\sim}10{\mu}M$) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing $AT_1R$. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through $AT_1R$.