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Effects of water extract of Paeoniae Radix Alba on a thioacetamide induced acute liver injury rat model (Thioacetamide 유발 급성 간손상 동물모델에 백작약 열수 추출물이 미치는 효능)

  • Lee, Se Hui;Shin, Mi-Rae;Lee, Ji Hye;Roh, Seong-Soo
    • Journal of Nutrition and Health
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    • v.54 no.2
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    • pp.224-237
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    • 2021
  • Purpose: Paeonia Radix Alba is a traditional herbal medicine used to treat the liver and the spleen. Many studies have reported that Paeonia Radix Alba extract (PR) affects liver injury, but there has been no study on liver injuries induced by thioacetamide (TAA). Therefore, we aimed at evaluating the effect of PR on a TAA-induced acute liver injury (ALI) model. Methods: The antioxidant activity of PR was assayed by the content of total polyphenol, total flavonoid, 1,1-diphenyl-2'-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonicacid) (ABTS) radical scavenging activities in vitro test. ALI was induced via-intraperitoneal injection of TAA (200 mg/kg body weight) for three consecutive days. Also, silymarin (100 mg/kg body weight) and PR (100 or 200 mg/kg body weight) were administered at 1 hours 30 minutes prior to TAA treatment. The levels of ammonia, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were analyzed using an assay kit. The expressions of antioxidant proteins including Nrf2, Keap1, HO-1, SOD, catalase, and GPx-1/2 and oxidative stress-related proteins including NOX2, p47phox, and p22phox were evaluated by the western blot analysis. Results: PR showed excellent antioxidant activity in vitro. TAA administration increased the levels of ammonia, GOT, and GPT in the ALI control group compared to the normal group, whereas it was significantly reduced by PR pretreatment. Moreover, NADPH oxidase protein expressions were upregulated after TAA treatment, while the elevated expressions were inhibited by PR pretreatment. The expressions of antioxidant protein were downregulated in the ALI control group, whereas Nrf2 activation in the PR group was accompanied by increased levels of antioxidant enzymes. Conclusion: PR administration increased the antioxidant enzymes via activation of the Keap1/Nrf2 pathway and inhibited the protein levels of NADPH oxidase factors. Taken together, these results showed that PR treatment may be considered to ameliorate acute liver injury induced by TAA.

Numerical Study of SPGD-based Phase Control of Coherent Beam Combining under Various Turbulent Atmospheric Conditions (대기외란에 따른 SPGD 기반 결맞음 빔결합 시스템 위상제어 동작성능 분석)

  • Kim, Hansol;Na, Jeongkyun;Jeong, Yoonchan
    • Korean Journal of Optics and Photonics
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    • v.31 no.6
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    • pp.247-258
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    • 2020
  • In this paper, based on a stochastic parallel gradient descent (SPGD) algorithm we study phase control of a coherent-beam-combining system under turbulent atmospheric conditions. Based on the statistical theory of atmospheric turbulence, we carry out the analysis of the phase and wavefront distortion of a laser beam propagating through a turbulent atmospheric medium. We also conduct numerical simulations of a coherent-beam-combining system with 7- and 19-channel laser beams distorted by atmospheric turbulence. Through numerical simulations, we characterize the phase-control characteristics and efficiency of the coherent-beam-combining system under various degrees of atmospheric turbulence. It is verified that the SPGD algorithm is capable of realizing 7-channel coherent beam combining with a beam-combining efficiency of more than 90%, even under the turbulent atmospheric conditions up to cn2 of 10-13 m-2/3. In the case of 19-channel coherent beam combining, it is shown that the same turbulent atmospheric conditions result in a drastic reduction of the beam-combining efficiency down to 60%, due to the elevated impact of the corresponding refractive-index inhomogeneity. In addition, by putting together the number of iterations of the SPGD algorithm required for phase locking under atmospheric turbulence and the time intervals of atmospheric phenomena, which typically are of the order of ㎲, it is estimated that hundreds of MHz to a few GHz of computing bandwidth of SPGD-based phase control may be required for a coherent-beam-combining system to confront such turbulent atmospheric conditions. We expect the results of this paper to be useful for quantitatively analyzing and predicting the effects of atmospheric turbulence on the SPGD-based phase-control performance of a coherent-beam-combining system.

UHRF1 Induces Methylation of the TXNIP Promoter and Down-Regulates Gene Expression in Cervical Cancer

  • Kim, Min Jun;Lee, Han Ju;Choi, Mee Young;Kang, Sang Soo;Kim, Yoon Sook;Shin, Jeong Kyu;Choi, Wan Sung
    • Molecules and Cells
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    • v.44 no.3
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    • pp.146-159
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    • 2021
  • DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.

Caulerpa okamurae ethanol extract improves the glucose metabolism and insulin sensitivity in vitro and in vivo (옥덩굴 에탄올 추출물의 당 대사 및 인슐린 민감성 개선효과)

  • Park, Chul-Min;Thakuri, Laxmi Sen;Rhyu, Dong-Young
    • Journal of Applied Biological Chemistry
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    • v.64 no.1
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    • pp.89-96
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    • 2021
  • The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.

Evaluation of shrimp protein hydrolysate and krill meal supplementation in low fish meal diet for red seabream (Pagrus major)

  • Gunathilaka, Buddhi E.;Khosravi, Sanaz;Shin, Jaebeom;Shin, Jaehyeong;Herault, Mikael;Fournier, Vincent;Lee, Kyeong-Jun
    • Fisheries and Aquatic Sciences
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    • v.24 no.3
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    • pp.109-120
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    • 2021
  • Protein hydrolysates and krill meal (KM) are used as protein sources in aquafeeds. The study was conducted to examine the supplemental effects of shrimp protein hydrolysates (SH) or KM in a high-plant-protein diet for red seabream (Pagrus major). A fish meal (FM)-based diet (40%) was considered as the high-FM diet (HFM) and a diet containing 25% FM and soy protein concentrate, in the expense of FM protein from HFM diet, was considered as the low fish meal (LFM) diet. Two other experimental diets (SH and KM) were prepared by including SH and KM into LFM diet at 5% inclusion levels in exchange of 5% FM from the LFM diet. A feeding trial was conducted for fifteen weeks using triplicate group of fish (Initial mean body weight, 8.47 ± 0.05 g) for a diet. Growth performance and feed efficiency of fish were significantly enhanced by HFM, KM and SH supplemented diets over those of fish fed LFM diet. Interestingly, these parameters of fish fed SH diet showed better performance than KM and HFM groups. Liver IGF-I expression of fish fed SH diet was comparable to HFM group and higher than KM and LFM diets. Protein digestibility of SH diet was significantly higher than KM, HFM, and LFM diets. Dry matter digestibility of SH diet was comparable to HFM diet and significantly higher than KM and LFM diets. Nitro blue tetrazolium and superoxide dismutase activities of HFM, SH and KM groups were significantly elevated than the LFM group and SH diet increased catalase and glutathione peroxidase activities of fish compared to KM and LFM groups. Hemoglobin level and hematocrit of fish fed SH and KM diets were significantly higher than LFM group. A diet containing 20% FM with KM is comparable to a HFM diet which contains 40% FM for red seabream. SH can be used to replace FM from red seabream diet down to 20% and fish performance can be improved better than a diet containing 40% FM. Overall, it seems that SH is more effective ingredient in red seabream diet compared to KM.

Comparison of Blood Gas, Biochemical Factors, and Hormone Concentrations, and Muscle Stress Response Factors of Chickens in General Farms and Animal Welfare Farms (일반농장과 동물복지농장 닭의 혈액 내 gas, 생화학인자, 호르몬 농도 및 근육 내 스트레스 반응인자 비교)

  • Kim, Hee-Eun;Park, Jin-Ryong;Lee, Jeong-Eun;Kang, Da-Rae;Jang, Ae-Ra;Choe, Ho-Sung;Shim, Kwan-Seob
    • Korean Journal of Organic Agriculture
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    • v.29 no.3
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    • pp.415-427
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    • 2021
  • It is generally recognized that high stocking density can increase the risk of immune dysfunction and reduction in productivity cause of elevated stress in broiler farm. The domestic livestock industry is implementing a certification system for animal welfare and livestock farms to reduce the problem of dense breeding. This study compared broiler from the general farm and animal welfare farm to confirm the effectiveness of animal welfare farms against stress. Gas concentrations in a farm of general and animal welfare farms were analyzed, blood (n=10) of the 28-day-old broiler was collected, the partial pressure of the gas in the blood was analyzed using whole blood, and biochemical factors and hormones were analyzed using the serum. Glycogen and L-lactate are analyzed using ELISA kit on finely pulverized muscles (n=10). CO2 and NH3 levels in the farm were significantly higher in general farm. Partial carbon dioxide tension (PCO2) in blood was significantly higher and partial oxygen tension (PO2) was significantly lower in the general farm. Creatinine (CREA), glucose (GLU), aspartateaminotransferase (AST), and creatinekinase (CK) in the blood were significantly higher in the general farm, and total protein (TP) and globulin (GLOB) were significantly higher in animal welfare farm. Blood corticosterone and norepinephrine were significantly higher in general farm and epinephrine was significantly higher in animal welfare farm. These results imply that animal welfare farm provides a stress-reduced breeding environment.

Dietary zinc supplementation in high-fat diet-induced obese mice: Effects on the skeletal muscle ZIP7 expression and blood glucose regulation (고지방식이 유도 비만 마우스에서 아연 보충이 골격 근육의 아연 수송체 ZIP7 수준과 혈당 조절에 미치는 영향)

  • Zhu, Qianjing;Chung, Jayong
    • Journal of Nutrition and Health
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    • v.54 no.6
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    • pp.594-602
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    • 2021
  • Purpose: The zinc transporter ZIP7 is known to regulate glucose metabolism in skeletal muscles, and skeletal muscles are known to play a critical role in glycemic control. The present study examines the effects of dietary zinc supplementation on the blood glucose concentration and expression of ZIP7 in skeletal muscle obtained from obese mice fed a high-fat diet (HF). Methods: C57BL/6J male mice were divided into three groups and were administered either a HF (60% of total calories from fat), HF supplemented with zinc (HF+Zn, 60% calories from fat + 300 mg zinc/kg diet), or low-fat diet (CON, 10% calories from fat), for 15 weeks. Results: Compared to CON group mice, the final body weights and adipose tissue weights were significantly increased, while the skeletal muscle weights were significantly decreased in mice belonging to the HF and HF+Zn groups. The HF+Zn group had significantly lower levels of fasting blood glucose concentrations than the HF group. Similarly, zinc supplementation significantly decreased the HF-elevated area under the curve values obtained from the oral glucose tolerance test. Skeletal muscle protein levels of ZIP7 in samples obtained from the HF group were significantly decreased as compared to the CON group. Conversely, the skeletal ZIP7 protein levels in the HF+Zn group were significantly increased as compared to the HF group. Moreover, the protein levels of phosphorylated-AKT and glucose transporter 4 in the skeletal muscle were significantly increased subsequent to zinc supplementation. Conclusion: Our data demonstrates that zinc supplementation up-regulates the skeletal muscle ZIP7 expression, which is associated with improved glucose tolerance in the obesity.

Risk-Scoring System for Prediction of Non-Curative Endoscopic Submucosal Dissection Requiring Additional Gastrectomy in Patients with Early Gastric Cancer

  • Kim, Tae-Se;Min, Byung-Hoon;Kim, Kyoung-Mee;Yoo, Heejin;Kim, Kyunga;Min, Yang Won;Lee, Hyuk;Rhee, Poong-Lyul;Kim, Jae J.;Lee, Jun Haeng
    • Journal of Gastric Cancer
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    • v.21 no.4
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    • pp.368-378
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    • 2021
  • Purpose: When patients with early gastric cancer (EGC) undergo non-curative endoscopic submucosal dissection requiring gastrectomy (NC-ESD-RG), additional medical resources and expenses are required for surgery. To reduce this burden, predictive model for NC-ESD-RG is required. Materials and Methods: Data from 2,997 patients undergoing ESD for 3,127 forceps biopsy-proven differentiated-type EGCs (2,345 and 782 in training and validation sets, respectively) were reviewed. Using the training set, the logistic stepwise regression analysis determined the independent predictors of NC-ESD-RG (NC-ESD other than cases with lateral resection margin involvement or piecemeal resection as the only non-curative factor). Using these predictors, a risk-scoring system for predicting NC-ESD-RG was developed. Performance of the predictive model was examined internally with the validation set. Results: Rate of NC-ESD-RG was 17.3%. Independent pre-ESD predictors for NC-ESD-RG included moderately differentiated or papillary EGC, large tumor size, proximal tumor location, lesion at greater curvature, elevated or depressed morphology, and presence of ulcers. A risk-score was assigned to each predictor of NC-ESD-RG. The area under the receiver operating characteristic curve for predicting NC-ESD-RG was 0.672 in both training and validation sets. A risk-score of 5 points was the optimal cut-off value for predicting NC-ESD-RG, and the overall accuracy was 72.7%. As the total risk score increased, the predicted risk for NC-ESD-RG increased from 3.8% to 72.6%. Conclusions: We developed and validated a risk-scoring system for predicting NC-ESD-RG based on pre-ESD variables. Our risk-scoring system can facilitate informed consent and decision-making for preoperative treatment selection between ESD and surgery in patients with EGC.

Zinc Deficiency Elevates Fecal Protein, But Not Electrolyte and Short-Chain Fatty Acid, Levels in Enterotoxigenic Escherichia coli-Induced Diarrhea in Rats

  • David, Ebuka E.;Yameen, Muhammad A.;Igwenyi, Ikechuku O.;David, Chidinma N.;Nwobodo, Valentine;Ismail, Akindele K.
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.1
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    • pp.79-86
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    • 2022
  • Purpose: To determine the effect of zinc deficiency on fecal protein, electrolyte, and short-chain fatty acid levels in both heat-stable (ST) and heat-labile (LT) enterotoxigenic Escherichia coli (ETEC)-induced diarrhea in rats. Methods: Albino rats, weighing 100 to 150 g, were divided into 2 groups, with 15 animals each: non-zinc and zinc-deficient. These two groups were sub-divided into three sub-groups with five rats each: control (saline); LT-ETEC; and ST-ETEC. Sodium phytate (30 mmol/L) was added to the animals' water to induce zinc deficiency, while diarrhea was induced using 5×109 ETEC cells/mL. Fecal protein levels were estimated using the Bradford method, while sodium and potassium levels were determined using atomic absorption spectrophotometry. Short-chain fatty acids were measured using gas chromatography-mass spectrometry. Results: Among the non-zinc and zinc-deficient groups, there were significant increases (p=0.04), (p=0.03) in fecal protein concentrations (mg/mL) in the LT-ETEC- (4.50±0.33), (6.50±0.26) and ST-ETEC- (3.85±0.19), (5.98±0.32) induced groups compared to the control groups (2.60±0.52), (3.50±0.11) respectively. Fecal sodium and potassium levels (mg/L) were significantly (p=0.029) increased in non-zinc-deficient rats induced with LT-ETEC (9.35±0.95, 1.05±0.48), and ST-ETEC (9.96±1.02, 1.21±0.45) compared with the control group (8.07±0.44, 0.47±0.17) but the increase were not statistically significant (p=0.059) in the zinc deficient rat groups. Fecal acetate and propionate levels (mg/g) significantly (p=0.032) increased when induced with LT-ETEC and ST-ETEC in non-zinc and zinc-deficient groups compared with the control groups. Conclusion: Zinc deficiency among rats with ETEC-induced diarrhea elevated fecal protein loss but may not have an effect on fecal sodium, potassium and short-chain fatty acid levels.

Comprehensive investigations of key mitochondrial metabolic changes in senescent human fibroblasts

  • Ghneim, Hazem K.;Alfhili, Mohammad A.;Alharbi, Sami O.;Alhusayni, Shady M.;Abudawood, Manal;Aljaser, Feda S.;Al-Sheikh, Yazeed A.
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.4
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    • pp.263-275
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    • 2022
  • There is a paucity of detailed data related to the effect of senescence on the mitochondrial antioxidant capacity and redox state of senescent human cells. Activities of TCA cycle enzymes, respiratory chain complexes, hydrogen peroxide (H2O2), superoxide anions (SA), lipid peroxides (LPO), protein carbonyl content (PCC), thioredoxin reductase 2 (TrxR2), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPx1), glutathione reductase (GR), reduced glutathione (GSH), and oxidized glutathione (GSSG), along with levels of nicotinamide cofactors and ATP content were measured in young and senescent human foreskin fibroblasts. Primary and senescent cultures were biochemically identified by monitoring the augmented cellular activities of key glycolytic enzymes including phosphofructokinase, lactate dehydrogenase, and glycogen phosphorylase, and accumulation of H2O2, SA, LPO, PCC, and GSSG. Citrate synthase, aconitase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, and complex I-III, II-III, and IV activities were significantly diminished in P25 and P35 cells compared to P5 cells. This was accompanied by significant accumulation of mitochondrial H2O2, SA, LPO, and PCC, along with increased transcriptional and enzymatic activities of TrxR2, SOD2, GPx1, and GR. Notably, the GSH/GSSG ratio was significantly reduced whereas NAD+/NADH and NADP+/NADPH ratios were significantly elevated. Metabolic exhaustion was also evident in senescent cells underscored by the severely diminished ATP/ADP ratio. Profound oxidative stress may contribute, at least in part, to senescence pointing at a potential protective role of antioxidants in aging-associated disease.