• 제목/요약/키워드: mechanisms and effects of drugs

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Activation of SAPK and Increase in Bak Levels during Ceramide and Indomethacin-Induced Apoptosis in HT29 Cells

  • Kim, Ju-Ho;Oh, Sae-Ock;Jun, Sung-Sook;Jung, Jin-Sup;Woo, Jae-Suk;Kim, Yong-Keun;Lee, Sang-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • 제3권1호
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    • pp.75-82
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    • 1999
  • It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time- dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, $Bcl-X_L,$ Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.

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국내 노인의 가정 내 비의도적 손상예방을 위한 중재의 역할: 주제범위 문헌고찰 (Role of Interventions in Preventing Unintentional Home Injuries of Older Adults in Korea: A Scoping Review)

  • 조옥희;황경혜;김혜경
    • 가정∙방문간호학회지
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    • 제31권1호
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    • pp.16-29
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    • 2024
  • Purpose: This scoping review aimed to synthesize the characteristics and effects of interventions designed to prevent unintentional home injuries in older adults in Korea. Methods: The review was conducted following the Joanna Briggs Institute protocol. A literature search was performed for studies published between 2001 and 2022 in the DBPia, RISS, KMBase, and NDSL databases. A total of 1,620 studies were identified, and 27 studies were included in the final analysis. Data were analyzed for characteristics of the literature, intervention-related unintentional injury mechanisms, and safety areas. Results: Most selected studies utilized a quasi-experimental design and targeted elderly women. In terms of injury mechanisms, 21 of 27 studies focused on falls, 2 on fire/disaster, 3 on drugs, and 1 on food. The most common preventive intervention for falls was exercise, and its effectiveness was verified using physical safety variables. Interventions in the fire/disaster, drug, and food domains were all educational, and changes in knowledge, behavior, and attitude were verified. Conclusion: This study confirmed the effectiveness of interventions for preventing unintentional injuries in the homes of community-dwelling older adults. These findings can serve as a foundation for developing and implementing unintentional injury prevention interventions at home for community-dwelling older adults. Multidisciplinary research is needed to address multifaceted safety issues by considering the home environment and injury risk factors.

Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced inflammatory responses through modulation of NF-${\kappa}B$/AP-1/PI3K-Akt signaling cascades in RAW 264.7 cells

  • Park, Chung Mu;Song, Young-Sun
    • Nutrition Research and Practice
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    • 제7권6호
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    • pp.423-429
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    • 2013
  • Luteolin is a flavonoid found in abundance in celery, green pepper, and dandelions. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-inflammatory capacity of luteolin and one of its glycosidic forms, luteolin-7-O-glucoside, were compared and their molecular mechanisms of action were analyzed. In lipopolysaccharide (LPS)-activated RAW 264.7 cells, luteolin more potently inhibited the production of nitric oxide (NO) and prostaglandin E2 as well as the expression of their corresponding enzymes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) than luteolin-7-O-glucoside. The molecular mechanisms underlying these effects were investigated to determine whether the inflammatory response was related to the transcription factors, nuclear factor (NF)-${\kappa}B$ and activator protein (AP)-1, or their upstream signaling molecules, mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K). Luteolin attenuated the activation of both transcription factors, NF-${\kappa}B$ and AP-1, while luteolin-7-O-glucoside only impeded NF-${\kappa}B$ activation. However, both flavonoids inhibited Akt phosphorylation in a dose-dependent manner. Consequently, luteolin more potently ameliorated LPS-induced inflammation than luteolin-7-O-glucoside, which might be attributed to the differentially activated NF-${\kappa}B$/AP-1/PI3K-Akt pathway in RAW 264.7 cells.

Paris polyphylla Smith Extract Induces Apoptosis and Activates Cancer Suppressor Gene Connexin26 Expression

  • Li, Fu-Rong;Jiao, Peng;Yao, Shu-Tong;Sang, Hui;Qin, Shu-Cun;Zhang, Wei;Zhang, Ya-Bin;Gao, Lin-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권1호
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    • pp.205-209
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    • 2012
  • Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.

생식 · 발생독성시험의 방법적 고찰과 최신 연구 동향 (The Recommended Approaches and Recent Trends in Reproductive and Developmental Toxicology)

  • 곽승준;조대현
    • Toxicological Research
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    • 제21권4호
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    • pp.271-278
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    • 2005
  • Reproductive and developmental toxicology is concerned with various physical or chemical agents interfering with fertility in both gender or normal growth of offsprings. Reproductive and developmental toxicology is rather a complex science, with many fields, i.e., various endpoints are involved and many different mechanisms of action. For that reason, diverse aspects must be considered when attempting to assess possible adverse health effects in the area of reproductive and developmental toxicology. The thalidomide tragedy made it clear to regulatory authorities around the world that systematic, comprehensive evaluation of the reproductive cycle was needed to adequately evaluate the potential of medicinal drugs to impair the process of reproduction or the development of embryos, fetuses, and children. International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) and U.S. Food and Drug Administration (FDA) developed a guideline to assess the reproductive and developmental toxicity. Also these guidelines have since been applied to the detection and regulation of environmental toxicants, food additives, and so on. Although it was hoped that testing procedures of guideline would be updated constantly to reflect the current state of the science in reproductive and developmental toxicology, it was not until this decade that regulatory guidelines and testing methods have been altered in a significant way. In this paper, we would like to present the recommended approaches and recent trends for improvement of testing guidelines or experimental methods in reproductive and developmental toxicology.

BALB/C Mice에서 노루궁뎅이버섯 균사체 보충이 LPS로 인한 산화적 스트레스와 염증 반응에 미치는 효과 및 기전 (Effect of Hericium erinaceus Mycelia Supplementation on the Oxidative Stress and Inflammation Processes Stimulated by LPS and Their Mechanisms in BALB/C Mice)

  • 장지현;노경희;최지나;진경숙;신진혁;온준호;조정원;정우식;김묘정;송영선
    • 한국식품영양과학회지
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    • 제39권2호
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    • pp.227-236
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    • 2010
  • 본 연구는 in vivo에서의 6주령의 BALB/C 생쥐(평균체중 $24.73\pm0.11$ g)에게 1주일 간 노루궁뎅이버섯 균사체(Hericium erinaceus mycelia)를 첨가한 식이를 급여한 후 내독소인 LPS로 인한 산화적 스트레스 및 염증반응에 미치는 영향을 조사하고자 하였다. 실험군은 5군으로 분류하였으며 정상 대조군(NC)과 양성 대조군(LC)은 chow를, HMP 10%군과 HMP 3%군은 chow에 노루궁뎅이버섯 균사체를 각각 3%와 10%를 첨가하였으며 HMP 대조군(HMP-C)은 chow에 노루궁뎅이버섯 균사체를 10% 첨가하여 pellet 형태로 조제하여 1주일 간 각각의 실험 식이를 급여하였다. LC군과 HMP 3% 및 HMP 10%군은 각각 LPS(100 mg/kg BW)를 투여하였으며 NC군과 HMP-C군은 생리식염수를 LPS와 동일한 농도로 투여하였다. 실험동물의 식이효율은 노루궁뎅이버섯 균사체를 보충한 군에서 저하되었으며 노루궁뎅이버섯 균사체의 보충군에서 체중감소 효과를 보였다. 노루궁뎅이버섯 균사체 10%를 보충한 HMP-C군과 HMP 10%군은 분변의 배설량이 가장 많았고 분변 중 총지방 양은 노루궁뎅이버섯 균사체를 섭취한 군에서 높은 수준을 보였으나 섭취량에 따른 현저한 차이는 보이지 않았고, 혈장 TG 함량은 군 간에 유의적인 차이는 보이지 않았으나 노루궁뎅이버섯 균사체 10%를 첨가한 식이를 섭취한 군에서 다소 높은 경향을 보였다. 분변 100 g 당 $\beta$-glucan의 함량은 노루궁뎅이버섯 균사체 3%를 보충한 군에서 가장 높았다. 혈장의 ALT 수준은 LPS를 투여한 후 8시간 경과 후에는 LC군에서 현저하게 증가한 반면 노루궁뎅이버섯 균사체를 첨가한 식이를 급여한 HMP 3%와 HMP 10%군에서는 유의적으로(p<0.05) 저하되어 NC군과 비슷한 수준을 보였다. 간에서의 SOD, GSH-red, GSH-px 활성은 LPS 투여 후 LC군에 비해 노루궁뎅이버섯 균사체를 섭취한 군에서 증가하였으며 GSH-red의 단백질 발현과 GSH 함량 또한 높아지는 것으로 나타났다. 이상의 결과로 미루어 볼 때 노루궁뎅이버섯 균사체의 보충은 내독소인 LPS로 유도된 산화적 스트레스에 저항하여 간 기능을 보호하는 효과가 있는 것으로 보이며 그 기전으로는 항산화 효소계 활성과 GSH-red 단백질 발현 증가, 그리고 GSH 수준 향상 등을 열거할 수 있다.

The Anti-inflammatory Mechanism of the Peel of Zanthoxylum piperitum D.C. is by Suppressing NF-κB/Caspase-1 Activation in LPS-Induced RAW264.7 Cells

  • Choi, Yun-Hee;Myung, Noh-Yil
    • 한국자원식물학회지
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    • 제32권6호
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    • pp.669-676
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    • 2019
  • Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E2 (PGE2), and caspase-1 using ELISA. The expression levels of inflammatory-related genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE2 and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.

Silicone breast implant modification review: overcoming capsular contracture

  • Shin, Byung Ho;Kim, Byung Hwi;Kim, Sujin;Lee, Kangwon;Choy, Young Bin;Heo, Chan Yeong
    • 생체재료학회지
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    • 제22권4호
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    • pp.319-327
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    • 2018
  • Background: Silicone implants are biomaterials that are frequently used in the medical industry due to their physiological inertness and low toxicity. However, capsular contracture remains a concern in long-term transplantation. To date, several studies have been conducted to overcome this problem. This review summarizes and explores these trends. Main body: First, we examined the overall foreign body response from initial inflammation to fibrosis capsule formation in detail and introduced various studies to overcome capsular contracture. Secondly, we introduced that the main research approaches are to inhibit fibrosis with anti-inflammatory drugs or antibiotics, to control the topography of the surface of silicone implants, and to administer plasma treatment. Each study examined aspects of the various mechanisms by which capsular contracture could occur, and addressed the effects of inhibiting fibrosis. Conclusion: This review introduces various silicone surface modification methods to date and examines their limitations. This review will help identify new directions in inhibiting the fibrosis of silicone implants.

BmKn-2 Scorpion Venom Peptide for Killing Oral Cancer Cells by Apoptosis

  • Tong-ngam, Pirut;Roytrakul, Sittiruk;Sritanaudomchai, Hathaitip
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권7호
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    • pp.2807-2811
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    • 2015
  • Scorpion venom peptides recently have attracted attention as alternative chemotherapeutic agents that may overcome the limitations of current drugs, providing specific cytotoxicity for cancer cells with an ability to bypass multidrug-resistance mechanisms, additive effects in combination therapy and safety. In the present study, BmKn-2 scorpion venom peptide and its derivatives were chosen for assessment of anticancer activities. BmKn-2 was identified as the most effective against human oral squamous cells carcinoma cell line (HSC-4) by screening assays with an $IC_{50}$ value of $29{\mu}g/ml$. The BmKn-2 peptide killed HSC-4 cells through induction of apoptosis, as confirmed by phase contrast microscopy and RT-PCR techniques. Typical morphological features of apoptosis including cell shrinkage and rounding characteristics were observed in treated HSC-4 cells. The results were further confirmed by increased expression of pro-apoptotic genes such as caspase-3, -7, and -9 but decrease mRNA level of anti-apoptotic BCL-2 in BmKn-2 treated cells, as determined by RT-PCR assay. In summary, the BmKn-2 scorpion venom peptide demonstrates specific membrane binding, growth inhibition and apoptogenic activity against human oral cancer cells.

Which Dosing Scheme is Suitable for the Taxanes\ulcorner An in Vitro Model

  • Sanli, Ulus-Ali;Uslu, Ruchan;Karabulut, Bulent;Sezgin, Canfeza;Saydam, Guray;Omay, Serdar-Bedii;Goker, Erdem
    • Archives of Pharmacal Research
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    • 제25권4호
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    • pp.550-555
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    • 2002
  • The discovery and development of the taxane class of antitumor compounds represent significant advances in the treatment of patients with a variety of malignancies. These drugs are effectively used in the treatment of breast cancer. In this study we evaluated the efficacy of fractionated usage of both paclitaxel and docetaxel as a single agent in the breast cancer cell line MCF-7. It has been shown that the cytotoxic effect of paclitaxel was increased when the divided $IC_{50}$ concentrations were used sequentially and in contrast to paclitaxel, cytotoxic effect of docetaxel was decreased with the same schema and the single dose of $IC_{50}$ concentration was optimal. The cause of the difference between the cytotoxic effects of two agents with this schedule is obscure. Demonstrating mechanisms, which are responsible for these differences, will be important for more rational use of taxoids and to provide basis for the following clinical trials.