• 제목/요약/키워드: $P2Y_{12}$ Inhibitors

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Interactive Effects of UV-B and Pesticides on Photosynthesis and Nitrogen Fixation of Anabaena doliolum

  • Chandrai, Lar;Vandana, Pandey
    • Journal of Microbiology and Biotechnology
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    • 제12권3호
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    • pp.423-430
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    • 2002
  • The effects of UV-B and commercial grade pesticides (butachlor and carbofuran), individually and in combination, were studied on a variety of physiological processes of rice field cyanobacterium Anabaena doliolum. Butachlor was found to be $2-12\%$ more toxic than carbofuran and $4-24\%$ than UV-B on the growth, photosynthesis, lipid peroxidation, membrane permeability, and nitrogenase activity of the test cyanobacterium. Of the three photosynthesis inhibitors, the butachlor-induced inhibition of whole chain was approximately 3 and $21\%$ higher than carbofuran and UV-B, respectively. Although the interaction of the stress factors caused a significant inhibition (P<0.01), it was still less than the additive effect on the parameters investigated, except for PSI.

Stanniocalcin 2 enhances mesenchymal stem cell survival by suppressing oxidative stress

  • Kim, Pyung-Hwan;Na, Sang-Su;Lee, Bomnaerin;Kim, Joo-Hyun;Cho, Je-Yoel
    • BMB Reports
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    • 제48권12호
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    • pp.702-707
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    • 2015
  • To overcome the disadvantages of stem cell-based cell therapy like low cell survival at the disease site, we used stanniocalcin 2 (STC2), a family of secreted glycoprotein hormones that function to inhibit apoptosis and oxidative damage and to induce proliferation. STC2 gene was transfected into two kinds of stem cells to prolong cell survival and protect the cells from the damage by oxidative stress. The stem cells expressing STC2 exhibited increased cell viability and improved cell survival as well as elevated expression of the pluripotency and self-renewal markers (Oct4 and Nanog) under sub-lethal oxidative conditions. Up-regulation of CDK2 and CDK4 and down-regulation of cell cycle inhibitors p16 and p21 were observed after the delivery of STC2. Furthermore, STC2 transduction activated pAKT and pERK 1/2 signal pathways. Taken together, the STC2 can be used to enhance cell survival and maintain long-term stemness in therapeutic use of stem cells.

넙치 (Paralichthys olivaceus) 뇌로부터 phospholipase D 활성 억제 단백질의 정제 및 특성 규명 (Purification and Characterization of Proteins Inhibiting Phospholipase D Activity from Flounder (Paralichthys olivaceus) Brain)

  • 서정수;김은희;황은영;김남득;김동선;이형호;정준기
    • 한국수산과학회지
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    • 제34권4호
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    • pp.370-377
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    • 2001
  • 본 연구에서는 넙치, Pafalichthys olivaceus 뇌 조직에서 인지질가수분해효소 D (phospholipase D, PLD) 활성의 특성 규명 및 이 활성을 억제하는 단백질을 분리 정제하여 그 특성을 규명하였다. 넙치 뇌 조직에서 PLD 활성이 관찰되었으며, 이 활성은 포스파티딜 이노시톨 비스인산염 (phosphatidyl-inositol 4,5-bisphos-phate, $PIP_2$)에 대해서 의존성을 나타내었으나, ADP-rebosylation factor (ARF)에 의해서는 영향을 받지 않았다. PLD 억제물은 넙치 뇌 조직의 세포질 분획물을 사용하여 여러 종류의 칼럼을 통하여 분리 정제하였고, 그 억제물의 분자크기 및 기작의 특성을 규명하였다. 마지막 chromatography을 통하여 여섯 개의 억제를 나타내는 분획물을 얻었으며, 이 중 두 개의 분획물인 IIA IIB는 $PIP_2$-phosphatase activities를 나타내었다. 이 중 IIA 분획물은 면역화학적 분석을 통하여 inositolpolyphosphate 5-phosphatase family로 알려져 있는 신경말단 단백질인 synaptojanin으로 동정되었다. 그리고 IIB fraction은 Superose 12 gel filtration chromatography을 통하여 158-kDa의 크기로 확인되었으며, 이것은 면역화학적 분석을 통하여 synaptojanin과는 별개의 단백질로 판명되었다. 또한, IIB 분획물은 $PIP_2$ phosphatase activity 확인 실험에서 대사산물로서 phosphatidylinositol phosphate (PIP)만을 생성하였다. 이 결과는 IIB 분획물이 $PIP_2$의 4혹은 5 위치의 인산 (phosphate) 중 어느 하나만을 선택적으로 가수분해시킨다는 것을 암시한다. 이상의 연구 결과들을 종합하여 보면, 넙치 뇌 조직에는 다양한 형태의 $PIP_2$-phosphatases가 존재하며, 이들은 $PIP_2$-의존적인 PLD 활성의 억제조절과정에서 중요한 역할을 할 것으로 사료된다.

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Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies

  • Qi, Wei-Xiang;Fu, Shen;Zhang, Qing;Guo, Xiao-Mao
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권19호
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    • pp.8177-8182
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    • 2014
  • Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

The Role of the Hydrophobic Group on Ring A of Chalcones in the Inhibition of Interleukin-5

  • Yang, Hyun-Mo;Shin, Hye-Rim;Cho, Soo-Hyun;Song, Gyu-Yong;Lee, In-Jeong;Kim, Mi-Kyeong;Lee, Seung-Ho;Ryu, Jae-Chun;Kim, Young-Soo;Jung, Sang-Hun
    • Archives of Pharmacal Research
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    • 제29권11호
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    • pp.969-976
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    • 2006
  • Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at $50\;{\mu}M,\;IC_{50}=25.3\;{\mu}M$) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c ($IC_{50}=12.6\;{\mu}M$), 2d ($IC_{50}=12.2\;{\mu}M$), and 2i ($IC_{50}=12.3\;{\mu}M$) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.

Expression of Acetohydroxyacid Synthase from Bacillus anthracis and Its Potent Inhibitors

  • Choi, Kyoung-Jae;Pham, Chien Ngoc;Jung, Hoe-Il;Han, Sung-Hwan;Choi, Jung-Do;Kim, Jin-Heung;Yoon, Moon-Young
    • Bulletin of the Korean Chemical Society
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    • 제28권7호
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    • pp.1109-1113
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    • 2007
  • Acetohydroxyacid synthase (AHAS, EC 2. 2. 1. 6) is the enzyme that catalyses the first step in the common pathway of the biosynthesis of the branched chain amino acids, valine, leucine and isoleucine. For the first time, the AHAS gene from Bacillus anthracis was cloned into the expression vector pET28a(+), and was expressed in the E. coli strain BL21(DE3). The purified enzyme was checked on 12% SDS-PAGE to be a single band with molecular weight of 65 kDa. The optimum pH and temperature for B. anthracis AHAS was at pH 7.5 and 37 oC, respectively. Kinetic parameters of B. anthracis were as follows: Km for pyruvate, K0.5 for ThDP and Mg2+ was 4.8, 0.28 and 1.16 mM respectively. AHAS from B. anthracis showed strong resistance to three classes of herbicides, Londax (a sulfonylurea), Cadre (an imidazolinone), and TP (a triazolopyrimidine). These results indicated that these herbicides could be used in the search for new anti-bacterial drugs.

Phorbol Ester-induced Contraction Through p38 Mitogen-activated Protein Kinase is Diminished in Aortas from DOCA-Salt Hypertensive Rats

  • Lee, Chang-Kwon;Kim, Jung-Kwan;Won, Kyung-Jong;Lee, Hwan-Myung;Kim, Hyo-Jin;Roh, Hui-Yul;Park, Hyo-Jun;Shin, Hwa-Sup;Park, Tae-Kyu;Kim, Bo-Kyung;Lee, Sang-Mok
    • Archives of Pharmacal Research
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    • 제29권11호
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    • pp.1024-1031
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    • 2006
  • The role of mitogen-activated protein kinase (MAPK) in the decreased contractile response to phorbol ester in aortic smooth muscle strips from deoxycorticosterone acetate (DOCA)-salt hypertensive rats was examined. Norepinephrine (NE) evoked greater contractility in aortic strips from DOCA rats than in those of sham-operated rats. 12-Deoxyphorbol 13-isobutyrate (DPB) induced contraction in $Ca^{2+}-free$ medium, which was diminished in strips from DOCA rats compared to sham-operated rats. Vasoconstrictions induced by these stimulants were inhibited by SB203580 and PD098059, inhibitors of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2, respectively, in both strips. The phosphorylation of p38 MAPK and ERK1/2 induced by NE was greater in strips from DOCA rats compared to those from sham-operated rats, and this phosphorylation was inhibited by the kinase inhibitors. DPB increased the phosphorylation of p38 MAPK and ERK1/2 in strips from both animals, and the increment of p38 MAPK phosphorylation by the stimulant was diminished in strips from DOCA rats compared to sham-operated rats. These findings suggest that the $Ca^{2+}-independent$ contraction evoked by DPB results from the activation of MAPKs in rat aortic smooth muscle and that the attenuated contractility by DPB in DOCA rat appears to be associated with diminished p38 MAPK activity.

Efficacy of proton pump inhibitors and H2 blocker in the treatment of symptomatic gastroesophageal reflux disease in infants

  • Azizollahi, Hamid Reza;Rafeey, Mandana
    • Clinical and Experimental Pediatrics
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    • 제59권5호
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    • pp.226-230
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    • 2016
  • Purpose: Gastroesophageal reflux disease (GERD) occurs in pediatric patients when reflux of gastric contents presents with troublesome symptoms. The present study compared the effects of omeprazole and ranitidine for the treatment of symptomatic GERD in infants of 2-12 months. Methods: This study was a clinical randomized double-blind trial and parallel-group comparison of omeprazole and ranitidine performed at Children Training Hospital in Tabriz, Iran. Patients received a standard treatment for 2 weeks. After 2 weeks, the patients with persistent symptoms were enrolled in this randomized study. Results: We enrolled 76 patients in the present study and excluded 16 patients. Thirty patients each were included in group A (ranitidine) and in group B (omeprazole). GERD symptom score for groups A and B was $47.17{\pm}5.62$ and $51.93{\pm}5.42$, respectively, with a P value of 0.54, before the treatment and $2.47{\pm}0.58$ and $2.43{\pm}1.15$, respectively, after the treatment (P=0.98). No statistically significant differences were found between ranitidine and omeprazole in their efficacy for the treatment of GERD. Conclusion: The safety and efficacy of ranitidine and omeprazole have been demonstrated in infants. Both groups of infants showed a statistically significant decrease in the score of clinical variables after the treatment.

카바메이트 중독 후 발생한 급성췌장염 (Acute Pancreatitis after Carbamate Poisoning)

  • 박요섭;김용원;오세현;차용성;차경철;김오현;이강현;황성오;김현
    • 대한임상독성학회지
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    • 제12권2호
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    • pp.77-84
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    • 2014
  • Purpose: Carbamate insecticides are potent cholinesterase inhibitors capable of causing severe cholinergic toxicity. Use of carbamate rather than organophosphate insecticides has been increasing. Compared with organophosphate poisoning, relatively few studies have investigated carbamate-associated acute pancreatitis. We investigated general characteristics and pancreatitis of carbamate poisoning and the predictors, among those readily assessed in the emergency department. Methods: We performed a retrospective review of consecutive patients, aged over 18 years, who were admitted between January 2008 and April 2012 to an emergency department (ED) of an academic tertiary care center for treatment of carbamate poisoning. Patients who exhibited poisoning by any other material, except alcohol, were excluded. After application of exclusion criteria, patients were divided according to carbamate-induced pancreatitis and non-pancreatitis groups. Results: A total of 41 patients were included in this study. Among these 41 patients, the prevalence of acute pancreatitis was 36.6% (15 patients). Initial blood chemistry tests showed a statistically higher glucose level in the pancreatitis group, compared with the non-pancreatitis group (222, IQR 189-284 vs. 137, IQR 122-175 mg/dL, P<0.05). Regarding clinical courses and outcomes, a significantly higher proportion of patients developed pneumonia [10 (66.7%) vs. 6 (23.1%), P<0.05] and had a longer hospital stay (7 days, IQR 6-12 vs. 5 days, IQR 2-11, P<0.05), but no difference in mortality, in the pancreatitis group vs. the non-pancreatitis group. In multivariate analysis, the initial glucose was showing significant association with the presentation of carbamate-induced acute pancreatitis (odds ratio 1.018, 95% confidence interval 1.001-1.035, P<0.05). Conclusion: Carbamate-induced acute pancreatitis is common, but not fatal. Initial serum glucose level is associated with acute pancreatitis.

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IL-12 and IL-23 Production in Toxoplasma gondii- or LPS-Treated Jurkat T Cells via PI3K and MAPK Signaling Pathways

  • Ismail, Hassan Ahmed Hassan Ahmed;Kang, Byung-Hun;Kim, Jae-Su;Lee, Jae-Hyung;Choi, In-Wook;Cha, Guang-Ho;Yuk, Jae-Min;Lee, Young-Ha
    • Parasites, Hosts and Diseases
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    • 제55권6호
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    • pp.613-622
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    • 2017
  • IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.