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Telmisartan Inhibits TNFα-Induced Leukocyte Adhesion by Blocking ICAM-1 Expression in Astroglial Cells but Not in Endothelial Cells

  • Jang, Changhwan;Kim, Jungjin;Kwon, Youngsun;Jo, Sangmee A.
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.423-430
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    • 2020
  • Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

Effect of in vitro Culture Condition and Lines on Growth Pattern of Lateral Bud from Nodal Cutting of Phalaenopsis Flower Stalk (팔레높시스 기내 화경 배양조건 및 계통이 액아의 발육형태에 미치는 영향)

  • 김미선;은종선;이영란
    • Korean Journal of Plant Tissue Culture
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    • v.28 no.4
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    • pp.189-195
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    • 2001
  • This study was carried out to investigate the effects of in vitro culture condition and among lines on growth pattern of lateral buds from nodal cuttings of Phalaenopsis flower stalks. The ratio of bud growing into shoot from nodal cuttings of flower stalks were 90.9% and 54.4% on MS and hyponex medium, respectively. The number of buds grown vegetatively were increased remarkably on the MS medium containing 5 mg/L BA. The rate of buds grown vegetatively was higher in basal and middle parts than in upper part of flower stalks. The flower stalk sections cultured at 25~28$^{\circ}C$ showed the highest ratio of vegetative growth. Medium contamination was decreased by pretreatment of etiolation to the flower stalk. However, the pretreatment did not show specific effects on shoot development and reduction of phenolic compound. Average shoot number which was formed from flower stalk segments in 27 of 30 accessions were 3.17, while high number of shoots were obtained from Phal. 3020 and Phal. 3039. The growth pattern of lateral buds in F$_1$hybrids was similar to that of their parents.

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Effect of Hydraulic Loading Rate of a Continuous Stirred Tank Reactor(CSTR) on the Removal Efficiency of Pollutants of Pig Slurry (CSTR의 수리학적 부하율이 돈슬러리의 유기물 및 영양염류 저감효율에 미치는 영향)

  • 정우철;최홍림
    • Journal of Animal Environmental Science
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    • v.5 no.3
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    • pp.189-196
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    • 1999
  • Anaerobic digestion is a naturally occuring microbial process involving the decomposition of organic materials such as livestock manure. This study explores the effect of the operating conditions, HRT (Hydraulic Retention Time) and feeding frequency on treatment efficiency for digestion of pig slurry, which has been one of most difficult organic waste for proper treatment in livestock production industry in Korea at the present time. The pilot-scale CSTR of 5 m3 in volume was designed. manufactured, and operated at the temperature of 35$\pm$1$^{\circ}C$. The digester was designed to hydraulically stir for complete mixing and to supply heat from the water bath to maintain mesophilic temperature. The HRT of the digester for Test 1 and Test 2, and Test 3 was set for 17 days and 13 days respectively and pig slurry was fed once a day with 300$\ell$ each for Test 1 and Test 3, while twice with 150$\ell$each for Test 2. Test 2 showed better performance by increase of 4% in VS removal efficiency and 5% in biogas production rate. This is mainly attributed to smaller temperature drop by feeding frequently with half amount, which eventually led to lesser impact on anaerobic mocrobes in the digester. Test 2 maintained optimum pH 7.8 which uplifted the activaton of sulfur-reduction bacteria, alkalinity of around 4,000mg/$\ell$, VA of over 3,000mg/$\ell$ for whole period of experiment. Further research may require to provide the practical operation strategy of anaerobic treatment system for treatment of pig slurry.

Effects of Fly Maggot Extracts on the Liver and Plasma Lipid in Rat Fed High-Fat Diets (고지방식이 유도된 흰쥐의 혈액지질 및 간에 관한 파리유충 추출물의 효과)

  • Park, Byung-Sung
    • Journal of the Korean Applied Science and Technology
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    • v.27 no.3
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    • pp.290-299
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    • 2010
  • The bioactive effects of ethanol extracts from fly maggot (ME) on reduction of plasma lipids levels in rats fed high-fat diets (Expt. Ⅰ), and on liver function recovery of hepatotoxicity rats by intraperitoneal injection of carbon tetrachloride ($CCl_4$) or by orally administration of alcohol (Expt. II) were investigated. In expt. I, twenty seven, male rat SDS(sprague dawley strain) were randomly assigned to three treated groups, including normal control group, HF (group with high fat diets which have no extracts) and HFE (HF plus orally administered doses of ME extract at 5.0 mg/100g of body weight). In expt. II, forty five, male rats (SDS) were randomly assigned to each of the five groups: T1 (control), T2 (intraperitoneal injection of $CCl_4$), T3 (intraperitoneal injection of $CCl_4$ after orally administered with ME), T4 (orally administered with combination of ME and alcohol), T5 (orally administration of ME after orally administered with alcohol). There were significant decreases in plasma (TAG), (TC), (LDL-C) in the HFE group with orally administered doses of ME at 5.0 mg/100g of body weight, respectively, however, the (HDL-C) were significantly increased in HFE group as compared to HF group with high fat diets which have no extracts (p<0.05). The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ${\gamma}$-glutamyl transferse(${\gamma}$-GTP) and bilirubin were highest in T2 or T3, and high in order T4 or T5, and lowest in T1 except for bilirubin which has same with T4, T5 (p<0.05). The high recovery of liver damage by $CCl_4$ from the light microscopic appearance was observed in rats (T3) with extracts, and also high in T4 than T5 by orally administrated with alcohol. In conclusion, the ethanol extracts from fly maggot may have a bioactive effects to prevent for human lipids disorder and alcoholic disease.

The Beneficial and Adverse Effects of Raloxifene in Menopausal Women: A Mini Review

  • Khorsand, Imaneh;Kashef, Reyhaneh;Ghazanfarpour, Masumeh;Mansouri, Elaheh;Dashti, Sareh;Khadivzadeh, Talat
    • Journal of Menopausal Medicine
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    • v.24 no.3
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    • pp.183-187
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    • 2018
  • Objectives: The present mini review aimed to summarize the existing knowledge regarding the beneficial and adverse effects of raloxifene in menopausal women. Methods: This study is a review of relevant publications about the effects of raloxifene on sleep disorder, depression, venous thromboembolism, the plasma concentration of lipoprotein, breast cancer, and cognitive function among menopausal women. Results: Raloxifene showed no significant effect on depression and sleep disorder. Verbal memory improved with administration of 60 mg/day of raloxifene while a mild cognitive impairment risk reduction by 33% was observed with administration of 120 mg/day of raloxifene. Raloxifene was associated with a 50% decrease in the need for prolapse surgery. The result of a meta-analysis showed a significant decline in the plasma concentration of lipoprotein in the raloxifene group compared to placebo (standardized mean difference, -0.43; 10 trials). A network meta-analysis showed that raloxifene significantly decreased the risk of breast cancer (relative risk, 0.572; 95% confidence interval, 0.327-0.881; P = 0.01). In terms of adverse effects of raloxifene, the odds ratio (OR) was observed to be 1.54 (P = 0.006), indicating 54% increase in the risk of deep vein thrombosis (DVT) while the OR for pulmonary embolism (PE) was 1.05, suggesting a 91% increase in the risk of PE alone (P = 0.03). Conclusions: Raloxifene had no significant effect on depression and sleep disorder but decreased the concentration of lipoprotein. Raloxifene administration was associated with an increased risk of DVT and PE and a decreased risk of breast cancer and pelvic organ prolapse in postmenopausal women.

Induction of Oral Tolerance to Japanese Cedar Pollen

  • Kim, Joung-Hoon;Mun, Yeun-Ja;Ahn, Seong-Hun;Park, Joung-Suk;Woo, Won-Hong
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.557-563
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    • 2001
  • Oral tolerance is thought to play a role in preventing allergic responses and immune-mediated diseases. An improved mouse model of the oral tolerance to Japanese cedar pollen (JCP) as antigen was developed in order to detect induction of the tolerance, and the immunological characteristics of this model were also elucidated. Oral tolerance was induced by C3H/ HeN mice given an oral administration of 10 mg JCP 7 days before immunization with an i.p. injection of 0.1 mg JCP in complete Freunds adjuvant (CFA). The effects of oral JCP on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected on day 7 or 14 after immunization. Oral tolerance to JCP was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. The tolerance was primarily concerned with the decreased serum levels of antigen-specific IgG. In these mice, oral administration of JCP also suppressed various immune responses to the antigen including delayed-type hypersensitivity (DTH), total Igl level and anti-JCP IgGl level. The suppression of these immune responses by the oral antigen was associated with a significant reduction in interleukin-4 (IL-4) production. These findings therefore indicate that this C3H/HeN mice model has potential use in detecting the induction of oral tolerance by JCP and suggest that this tolerance model may be effective in the treatment and prevention of allergic responses caused by the antigen.

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Expressional Modulation of Aquaporin 1 and 9 in the Rat Epididymis by an Anabolic-Androgenic Steroid, Nandrolone Decanoate

  • Lee, Ki-Ho
    • Development and Reproduction
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    • v.25 no.4
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    • pp.245-255
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    • 2021
  • The spermatozoa become mature in the epididymis which is divided into initial segment and caput, corpus, and cauda epididymis. The water movement across the epididymal epithelium is important for creating luminal microenvironment for sperm maturation. Aquaporins (Aqps) are water channel proteins, and expression of Aqps is regulated by androgens. The current research was focused to examine expressional regulation of Aqp1 and Aqp9 by an androgenic-anabolic steroid, nandrolone decanoate (ND). The ND at the low dose (2 mg/kg body weight/week) or high dose (10 mg) was subcutaneously administrated into male rats for 2 or 12 weeks. Transcript levels of Aqp1 and Aqp9 were determined by quantitative real-time polymerase chain reaction (PCR) analyses. In the initial segment, level of Aqp1 was decreased with 12 week-treatment, while Aqp9 level was decreased by the high dose treatment for 12 weeks. In the caput epididymis, Aqp9 expression was decreased by the low dose treatment. The 2 week-treatment resulted in an increase of Aqp1 level but a decrease of Aqp9 expression in the corpus epididymis. In the corpus epididymis, the 12 week-treatment at the low dose caused the reduction of Aqp1 and Aqp9 levels, but the high dose treatment resulted in an increase of Aqp1 expression and a decrease of Aqp9 level. In the cauda epididymis, Aqp1 expression was decreased by 2 and 12 week-treatments, while increases of Aqp9 levels was detected with the high dose treatment for 2 weeks and with 12 week-treatment. These findings indicate differential regulation of Aqp1 and Aqp9 expression among epididymal segments by ND.

Comparative effects of dietary functional nutrients on growth performance, meat quality, immune responses, and stress biomarkers in broiler chickens raised under heat stress conditions

  • Kim, Deok Yun;Kim, Jong Hyuk;Choi, Won Jun;Han, Gi Ppeum;Kil, Dong Yong
    • Animal Bioscience
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    • v.34 no.11
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    • pp.1839-1848
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    • 2021
  • Objective: The objective of the present study was to investigate the comparative effects of dietary functional nutrients including glutamine (Gln), chromium picolinate (Cr picolinate), vitamin C (Vit C), betaine (Bet), and taurine (Tau) on growth performance, meat quality, immune responses, and stress biomarkers in broiler chickens raised under heat stress conditions. Methods: A total of 420 21-d-old Ross 308 male broiler chickens (initial body weight = 866±61.9 g) were randomly allotted to 1 of 7 treatment groups with 6 replicates. One group was kept under thermoneutral conditions and was fed a basal diet (PC, positive control). Other 6 groups were exposed to a cyclic heat stress condition. One of the 6 groups was fed the basal diet (NC, negative control), whereas 5 other groups were fed the basal diet supplemented with 0.5% Gln, 500 ppb Cr picolinate, 250 mg/kg Vit C, 0.2% Bet, or 1.0% Tau. The diets and water were provided ad libitum for 21 d. Results: Broiler chickens in NC group had decreased (p<0.05) growth performance and immune responses measured based on cutaneous basophil hypersensitivity (CBH), but increased (p<0.05) stress responses measured based on feather corticosterone concentrations and blood heterophil:lymphocyte than those in PC group. However, none of dietary functional nutrients had a positive effect on growth performance of broiler chickens. Dietary supplementation of 250 mg/kg Vit C improved (p<0.05) CBH responses of broiler chickens, but other functional nutrients had no such an improvement in CBH responses. All functional nutrients decreased (p<0.05) stress responses of broiler chickens. Conclusion: Functional nutrients including Gln, Cr picolinate, Vit C, Bet, and Tau at the supplemental levels used in this study decrease stress responses of broiler chickens to a relatively similar extent. However, this reduction in stress responses could not fully ameliorate decreased productive performance of broiler chickens raised under the current heat stress conditions.

Ozone-produced Oxidants Improve Water Quality Parameters and Microbial Colony Counts in the Semi-Recirculating Aquaculture System for Olive Flounder Paralichthys olivaceus (반순환여과양식시스템에서 오존 유래 잔류산화물이 넙치(Paralichthys olivaceus) 사육수의 수질과 미생물에 미치는 영향)

  • Jung, Sangmyung;Park, Woogeun;Park, Seongdeok;Park, Jeonghwan;Kim, Jae-Won;Kim, Pyong-kih
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.54 no.5
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    • pp.751-760
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    • 2021
  • This study investigated the changes in water quality parameters and microbial colonies when ozone was applied to a semi-recirculating aquaculture system (semi-RAS) for the olive flounder Paralichthys olivaceus (500 g in average weight). Concentrations of ozone-produced oxidants (OPO) in rearing tanks were maintained at 0, 0.014, 0.025 mg/L as Cl2 for 26 days. Except total ammonia nitrogen, nitrite nitrogen, nitrate nitrogen, phosphate phosphorus, chemical oxygen demand, and total suspended solids decreased significantly with increasing OPO concentration in daily and weekly monitoring (P<0.05). Colony forming unit (CFU) counts of heterotrophic marine bacteria decreased in an OPO concentration-dependent manner. Overall reduction rates of microbial colonies in the treatments were 80% higher than those of the control (P<0.05). During the experiment, the OPO concentration-driven ozonation was reliably practiced without any adverse effects on the animals cultured in semi-RAS. Considering the biohazard, operating cost, and stability of ozonation, an OPO concentration of 0.014 mg/L would be sufficient to control water quality parameters and microbial colonies in a semi-RAS.

Anti-inflammatory Effect of Skate Collagen Peptide through Attenuation of Oxidative Stress (홍어 콜라겐 펩타이드의 산화적 스트레스 완화를 통한 항염증효과)

  • Jeong, Kap Seop;Noh, Jeong Sook
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.4
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    • pp.1369-1378
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    • 2018
  • The purpose of this study was to investigate the effect of skate skin collagen peptide (SCP) according to its molecular weight (<1,000 Da or >1,000 Da) which was divided using the ultrafilatration method. The 200 mg/kg collagen peptide was administrated to obesity-induced db/db mice for 8 weeks. As the results, in collagen peptide-treated groups, body weight gain was decreased, the plasma and hepatic concentration of reactive oxygen species decreased and oxidative stress was alleviated. In addition, SCP-treated group showed the significant reduction of the protein expressions of nuclear transcription factors($NF-{\kappa}B$), enzymes(COX2, iNOS), and inflammatory cytokine(IL-6) in hepatic tissue, compared with those of the obese control group. There was a slight difference depending on the molecular weight of collagen peptide, but overall it was not significant. Therefore, SCP effectively inhibited the obesity-induced inflammatory response through attenuation of oxidative stress in the liver.