• Title/Summary/Keyword: functional effect

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Novel Isoquinolinamine and Isoindoloquinazolinone Compounds Exhibit Antiproliferative Activity in Acute Lymphoblastic Leukemia Cells

  • Roolf, Catrin;Saleweski, Jan-Niklas;Stein, Arno;Richter, Anna;Maletzki, Claudia;Sekora, Anett;Escobar, Hugo Murua;Wu, Xiao-Feng;Beller, Matthias;Junghanss, Christian
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.492-501
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    • 2019
  • Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

Analysis of the Convergence Pulmonary Function in the 20s Men of Mild Intellectual Disabilities with Obesity According to Position Changes (경도 지적장애를 가진 20대 남성 비만인의 자세변화에 따른 융합적인 폐기능에 대한 비교)

  • Park, Seung-Hwan;Kim, Ok-Ki;Seo, Kyo-Chul
    • Journal of the Korea Convergence Society
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    • v.10 no.10
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    • pp.67-74
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    • 2019
  • The purpose of this study was to determine whether changes of position might effect the convergence pulmonary function of the 20s men of mild intellectual disabilities with obesity. Ten subjects of mild intellectual disabilities with obesity(fat group) and ten contrary subjects without obesity(control group) were participated in the experiment. Subjects were assessed for their pulmonary function by using Fit mate according to the position changes(supine position, 45 lean sitting position, 90 sitting position). One-way repeated ANOVA analyzed each region data of pulmonary function of both the fat group and the control group according to their position changes. The result of the experiment showed that the 20s men of mild intellectual disabilities with obesity have lower pulmonary function than the contrary subjects in the each given posture. In comparison with three experimental positions, supine position was the lowest in the pulmonary function. This study showed the 20s men of mild intellectual disabilities with obesity have lower function of pulmonary volume than the control group, and thus, it suggests that the pulmonary functional data of 20s men of mild intellectual disabilities with obesity in this experiment can be used as a basic respiratory one for the various exercise programs in the area of the physical activities.

A Case Report of a Chronic Intracerebral Hemorrhage Patient with Obstinate Gait Disturbance Treated with Korean Medicine and Rehabilitation Exercise (완고한 보행장애를 주소로 하는 만성기 뇌출혈 환자의 한의 치료 및 재활 운동 증례보고 1례 : GAITRite®를 이용하여)

  • Chae, In-cheol;Choi, In-woo;Kim, Chan-young;Park, Mi-so;Park, Sang-soo;Jung, Eun-sun;Cha, Ji-yun;Jo, Hyun-kyung;Kim, Yoon-sik;Seol, In-chan;Yoo, Ho-ryong
    • The Journal of Internal Korean Medicine
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    • v.40 no.4
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    • pp.730-741
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    • 2019
  • Objective: The aim of this study was to report the effectiveness of traditional Korean medicine treatment with rehabilitation exercise on a chronic intracerebral hemorrhage patient with a severe gait disturbance. Method: The patient was treated with Korean herbal medicine (Gami-sibjeondaebo-tang) along with acupuncture, moxibustion, and rehabilitation exercise. The treatment effect was evaluated through the Manual Muscle Test (MMT) and the Korean version of the Modified Barthel Index (K-MBI). The gait of the patient was evaluated by Functional Ambulatory Category (FAC) and the Timed Up and Go (TUG) test. The spatiotemporal parameters were evaluated by a walkway system (GAITRite(R) system) and gait symmetry was evaluated by Symmetry Criterion (SC). Results: After 111 days of traditional Korean medicine treatment, the spatiotemporal parameters and symmetry of the patient's gait improved. Conclusion: This study suggested that traditional Korean medicine treatment with rehabilitation exercise could be effective for gait disturbance in patients with chronic intracerebral hemorrhage.

Influence of Application Method on Shear Bond Strength and Microleakage of Newly Developed 8th Generation Adhesive in Primary Teeth (새로 개발된 8세대 접착제의 적용 방법에 따른 유치에서의 전단결합강도와 미세누출)

  • Ryu, Wonjeong;Park, Howon;Lee, Juhyun;Seo, Hyunwoo
    • Journal of the korean academy of Pediatric Dentistry
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    • v.46 no.2
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    • pp.165-172
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    • 2019
  • The purpose of this study was to evaluate the effect of application time and phosphoric acid etching of 8th generation adhesives containing functional monomer on adhesive performance in primary teeth. 80 extracted non-carious human primary teeth were selected and divided into 8 groups based on 3 factors: (1) adhesive: G-Premio bond and Single bond universal; (2) application time: shortened time and manufacture's instruction; (3) acid etching mode: self-etching and total-etching. Shear bond strength was measured using a universal testing machine, and fractured surface were observed under scanning electron microscope. Microleakage was evaluated by dye penetration depth. G-Premio bond were not significant different in shear bond strength and microleakage depending on application time of adhesive and acid etching mode. In Single bond universal, shear bond strength of short application time was significantly lower than that of long adhesive application time (p = 0.014). Clinically applicable shear bond strength values (> 17 MPa) were identified in all groups. These results suggested that G-Premio bond be used clinically for a short application time without phosphoric acid etching.

Superhongmi bran extract improves lipid profile and menopause symptoms: a randomized, placebo-controlled clinical trial (슈퍼홍미 미강 추출물의 폐경 후 여성의 혈중 지질 농도 및 대사성 질환 개선 효과)

  • Chung, Soo Im;Nam, Su Jin;Liang, Jie;Ma, Jing Wen;Kang, Mi Young
    • Korean Journal of Food Science and Technology
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    • v.51 no.2
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    • pp.182-187
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    • 2019
  • Women who undergo natural menopause transition have increased numbers of risk factors relating to metabolic syndrome due to estrogen deficiency. This study was conducted to investigate the effect of Superhongmi bran extract on metabolic syndrome improvement in menopausal women. Thirty women, who participated in a randomized, double-blind, placebo-controlled trial, were assigned to placebo-control (n=15) or Superhongmi bran extract (n=15) groups and were asked to consume two tablets (350 mg per extract per tablet) per day. After 12 weeks, weight, body mass index (BMI), plasma triglyceride (TG) levels, and total cholesterol (TC) levels were significantly decreased, whereas HDL-cholesterol (HDL-C), apolipoprotein A1 (ApoA1), adiponectin, superoxide dismutase 1 (SOD1), and GSH (glutathione) concentrations were significantly increased in the Superhongmi bran extract group. Moreover, $17{\beta}-estradiol$, and progesterone levels in the Superhongmi group were significantly higher than those in the placebo-control group. These results suggest that Superhongmi bran extract alleviates metabolic symptom in menopausal women.

Triangular Resection of the Upper Lateral Cartilage for Middle Vault Deviation

  • Ryu, Gwanghui;Seo, Min Young;Lee, Kyung Eun;Hong, Sang Duk;Chung, Seung-Kyu;Dhong, Hun-Jong;Kim, Hyo Yeol
    • Clinical and Experimental Otorhinolaryngology
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    • v.11 no.4
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    • pp.275-280
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    • 2018
  • Objectives. Middle vault deviation has a significant effect on the aesthetic and functional aspects of the nose, and its management continues to be a challenge. Spreader graft and its modification techniques have been focused, but there has been scarce consideration for removing surplus portion and balancing the upper lateral cartilage (ULC). This study aimed to report the newly invented triangular-shaped resection technique ("triangular resection") of the ULC and to evaluate its efficacy for correcting middle vault deviation. Methods. A retrospective study included 17 consecutive patients who presented with middle vault deviation and underwent septorhinoplasty by using triangular resection at a tertiary academic hospital from February 2014 and March 2016. Their outcomes were evaluated pre- and postoperatively including medical photographs, acoustic rhinometry and subjective nasal obstruction using a 7-point Likert scale. Results. The immediate outcomes were evaluated around 1 month after surgery, and long-term outcomes were available in 12 patients; the mean follow-up period was 9.1 months. Nasal tip deviation angle was reduced from $5.66^{\circ}$ to $2.37^{\circ}$ immediately (P<0.001). Middle vault deviation also improved from $169.50^{\circ}$ to $177.24^{\circ}$ (P<0.001). Long-term results were $2.49^{\circ}$ (P=0.015) for nasal tip deviation and $178.68^{\circ}$ (P=0.002) for middle vault deviation. The aesthetic outcome involved a complete correction in eight patients (47.1%), a minimally visible deviation in seven patients (41.2%) and a remaining residual deviation in two patients (11.8%). Pre- and postoperative minimal cross-sectional areas (summation of the right and left sides) were 0.86 and 1.07, respectively (P=0.021). Fifteen patients answered about their nasal obstruction symptoms and the median symptom score had alleviated from 6.0 to 3.0 (P=0.004). Conclusion. Triangular resection of the ULC is a simple and effective method for correcting middle vault deviation and balancing the ULCs without complications as internal nasal valve narrowing.

Suppression of Lipopolysaccharide-Induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid in RAW 264.7 Macrophages and Zebrafish Larvae

  • Ji, Seon Yeong;Cha, Hee-Jae;Molagoda, Ilandarage Menu Neelaka;Kim, Min Yeong;Kim, So Young;Hwangbo, Hyun;Lee, Hyesook;Kim, Gi-Young;Kim, Do-Hyung;Hyun, Jin Won;Kim, Heui-Soo;Kim, Suhkmann;Jin, Cheng-Yun;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • v.29 no.6
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    • pp.685-696
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    • 2021
  • In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

Immuno-enhancing and Anti-obesity Effect of Abelmoschus manihot Root Extracts (금화규(Abelmoschus manihot) 뿌리 추출물의 면역증진 및 항비만효과)

  • Yu, Ju Hyeong;Geum, Na Gyeong;Ye, Joo Ho;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.34 no.5
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    • pp.411-419
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    • 2021
  • In this study, we investigated in vitro immune-enhancing and anti-obesity activity of Abelmoschus manihot roots (AMR) in mouse macrophage RAW264.7 cells and mouse adipocytes 3T3-L1 cells. AMR increased the production of immunostimulatory factors such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in RAW264.7 cells. The inhibition of toll like receptor (TLR) 2 and 4 blocked AMR-mediated production of immunostimulatory factors in RAW264.7 cells. In addition, the inhibition of mitogen-activated protein kinases (MAPKs) signaling pathway reduced AMR-mediated production of immunostimulatory factors. From these results, AMR is considered to have immune-enhancing activity through TLR2/4-mediated activation of MAPKs signaling pathway. In addition, AMR inhibited lipid accumulation and reduced the protein level such as CCAAT enhancer-binding protein alpha (CEBPα), peroxisome proliferator-activated receptor gamma (PPARγ), perilipin-1, adiponectin and fatty acid binding protein 4 (FABP4) associated with lipid accumulation in 3T3-L1 cells, indicating that AMR may have anti-obesity activity. Based on these results, AMR is expected to be used as a potential functional agent for immune enhancement and anti-obesity.

Dronedarone hydrochloride enhances the bioactivity of endothelial progenitor cells via regulation of the AKT signaling pathway

  • Zhang, Jian;Le, Thi Hong Van;Rethineswaran, Vinoth Kumar;Kim, Yeon-Ju;Jang, Woong Bi;Ji, Seung Taek;Ly, Thanh Truong Giang;Ha, Jong Seong;Yun, Jisoo;Cheong, Jae Hun;Jung, Jinsup;Kwon, Sang-Mo
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.5
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    • pp.459-466
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    • 2021
  • Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

Antioxidant and Anti-Inflammatory Activities of Ethanol Extract of Clematis trichotoma Nakai (할미밀망 에탄올 추출물의 항산화 및 항염증 활성 평가)

  • Jung, Jaemee;Shin, Mijoon;Jeong, Naeun;Hwang, Dahyun
    • Korean Journal of Clinical Laboratory Science
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    • v.53 no.2
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    • pp.165-173
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    • 2021
  • Clematis trichotoma Nakai (CTN) is a broad-leaved vine plant belonging to the family Ranunculus, native to Korea. Young leaves are used as food, and the stem and roots are used as medicinal materials. Antioxidant studies have been reported on the stems of CTN, but no studies have been conducted on the leaves. In this study, a 70% ethanol extract of CTN was prepared and its antioxidant and anti-inflammatory activities were investigated. For measuring the antioxidant activity, five assays (polyphenol and flavonoid content, reducing power, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity) were performed and CTN showed a concentration-dependent effect in all assays. To investigate the anti-inflammatory activity, we used RAW 264.7 cells. The concentrations (from 31.25 to 250 ㎍/mL) of CTN did not show cytotoxicity. CTN (250 ㎍/mL) inhibited dendritic transformation (34.4%) and also inhibited inflammation as seen by reduced levels of NO (77.4%), IL-6 (85.5%) and TNF-α (41.2%) compared to lipopolysaccharide (LPS). CTN (250 ㎍/mL) also suppressed the expression of the following genes: COX-2 (79.8%), iNOS2 (93.9%), IL-6 (87.6%), and TNF-α (77.3%) compared to LPS. These results demonstrated that CTN has excellent antioxidant and anti-inflammatory activities and can therefore be used as a natural biological resource.