• Title/Summary/Keyword: New drug development

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Repurposing Auranofin, an Anti-Rheumatic Gold Compound, to Treat Acne Vulgaris by Targeting the NLRP3 Inflammasome

  • Yang, Gabsik;Lee, Seon Joo;Kang, Han Chang;Cho, Yong-Yeon;Lee, Hye Suk;Zouboulis, Christos C.;Han, Sin-Hee;Ma, Kyung-Ho;Jang, Jae-Ki;Lee, Joo Young
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.437-442
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    • 2020
  • Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

Effects of the decoction water on the extraction of the bioactive compounds from rhubarb (전탕용수의 종류에 따른 대황 성분의 추출효과)

  • Jang, Yu-Seon;Chu, Van Men;Lee, Kwan-Jun;Seo, Eun-Young;Kim, Dong-Hee;Kang, Jong-Seong
    • Analytical Science and Technology
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    • v.24 no.1
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    • pp.38-44
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    • 2011
  • The quality of decoction water would be important for the preparation of herbal medicines. Four types of decoction water, S1, S2, S3 and S4, three types of mineral water from Jeju island and one type of tap water from Seoul region were evaluated. The contents of minerals in decoction water were analysed by ICP-AES and ICP-MS. There was significant difference in the mineral contents between the types of decoction water. The bioactive components from rhubarb were extracted with four types of water and the relationship between mineral contents in water and the extracted amounts of components was evaluated. The total extraction was calculated by evaporating water and weighing the residue. The bioactive components in rhubarb were determined by HPLC method. Kruskall-Wallis rank sum tests were used. Multiple factor analysis was used to analyze the relation between the contents of mineral and total extraction or bioactive components in the decocted solutions. Not only the total extraction but also the amount of extracted bioactive components showed statistically significant relationship with the contents of minerals and anions in decoction water.

Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats

  • Yu, Yeon Hee;Kim, Seong-Wook;Kang, Juhyeon;Song, Yejin;Im, yHyuna;Kim, Seo Jeong;Yoo, Dae Young;Lee, Man-Ryul;Park, Dae-Kyoon;Oh, Jae Sang;Kim, Duk-Soo
    • Journal of Korean Neurosurgical Society
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    • v.65 no.5
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    • pp.665-679
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    • 2022
  • Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

The effect of plasma treatment to improve adhesion strength of parylene-C coated medical grade SUS304 (Parylene-C 코팅된 의료용 SUS304 소재의 결합력 향상을 위한 플라즈마 처리 효과)

  • Kim, Dong-Guk;Song, Tae-Ha;Jeong, Yong-Hoon;Kang, Kwan-Su;Yoon, Deok-kyu;Kim, Min-Uk;Woo, Young-Jae;Seo, Yo-Han;Kim, Kyung-Ah;Roh, Ji-hyoung
    • Journal of the Korean institute of surface engineering
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    • v.55 no.6
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    • pp.390-397
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    • 2022
  • Parylene-C which was mainly used for industries such as electronics, machinery and semiconductors has recently been in the spotlight in the medical field due to its properties such as corrosion resistance and biocompatibility. In this study we intend to derive a plan to improve the bonding strength of Parylene-C coating with the SUS304 base material for medical use which can be applied to various medical fields such as needles, micro needles and in vitro diagnostic device sensors. Through plasma pretreatment the bonding strength between Parylene-C and metal materials was improved. It was confirmed that the coated surface was hydrophobic by measuring the contact angle and the improvement of the surface roughness of the sample manufactured through CNC machining was confirmed by measuring the surface roughness with SEM. Through the above results, it is thought that it will be effective in increasing usability and reducing pain in patients by minimizing friction when inserting medical devices and in contact with skin. In addition it can be applied to various application fields such as human implantable stents and catheters, and is expected to improve the performance and lifespan of medical parts.

Rifabutin Susceptibility and rpoB Gene Mutations in Multi-drug Resistant Mycobacterium Tuberculosis (다제내성 결핵균에서 Rifabutin감수성과 rpoB 유전자 돌연변이 양상의 비교 연구)

  • Shim, Tae-Sun;Kim, Jin-Sub;Park, Mi-Sun;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.6
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    • pp.853-869
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    • 2000
  • Background : Following several decades of decline, the incidence of tuberculosis has recent1y begun to increase in many countries of this the control of this disease has been impeded by the emergence of multi-drug resistant tuberculosis (MDR-TB). The development of rapid diagnostic methods and effective new drugs are needed to control MDR-TB. One of the new drugs for MDR-TB is rifabutin (RBU) which has been known to be effective in some patients with MDR-TB. A few reports showed that some types of mutations of the rpoB gene, which were known to be present in 96-98% of rifampicin-resistant M. tuberculosis, were associated with the rifampicin-resistant but RBU-susceptible phenotype. This study was performed to investigate the correlation between RBU susceptibility and the patterns of rpoB gene mutations in Korean MDR-TB. Methods : Sixty-five clinical isolates of multi-drug resistant Mycobacterium tuberculosis, gathered from patients who visited the Asan Medical Center from July 1997 to June 1999, were investigated. Clinical responses to rifabutin-containing regimen were evaluated. An RBU susceptibility test and sequencing analysis of rpoB gene were performed, and the results were analyzed to confirm which mutations correlated with RBU-susceptible MDR-TB. Results : Fifty-three of 56 (95%) clinical isolates of MDR-TB had 60 mutations of the rpoB gene. The most frequent mutations were found at codon 531 (43%), and two mutations were combined in seven clinical isolates. Five of 53 (10%) clinical isolates showed the RBU-susceptible phenotype, and in them the characteristic patterns of point mutations were found at codon 509, 516, and 526. Conclusion : The frequency and pattern of mutations of the rpoB gene of Korean MDR-TB isolates were similar to those in western countries, where the prevalence of tuberculosis is low, but some show RBU-susceptible phenotypes. RBU-susceptible MDR-TB isolates showed the characteristic pattern of mutations of the rpoB gene which could be used to rapidly diagnose RBU susceptibility.

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Impact of Postoperative Chemoradiotherapy and Chemoradiotherapy Alone for Esophageal Cancer in North-West Iran

  • Mirinezhad, Seyed Kazem;Somi, Mohammad Hossein;Shirmohamadi, Masoud;Seyednejad, Farshad;Jangjoo, Amir Ghasemi;Ghojazadeh, Morteza;Mohammadzadeh, Mohammad;Naseri, Ali Reza;Nasiri, Behnam
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3921-3924
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    • 2013
  • Background: To investigate the role of surgical treatment for locally advanced esophageal cancer, we compared the outcomes of chemoradiotheroy alone (CRT) to postoperative chemoradiotherapy (S/CRT), using, Regional Radiotherapy Center, database. Materials and Methods: This retrospective study was conducted in North-West of Iran, included of 255 consecutive patients with esophageal cancer. Eligible operable and non-operable, were treated with S/CRT and CRT respectively. Radiotherapy (RT) was delivered at 1.8-2 Gy/day for five consecutive days in a given week. Chemotherapy (CT) consisted of cisplatin and 5-fluorouracil. Results: From March 2006 to March 2011 255 patients: male/female 129/96, median age 68 (35-90), squamous/adeno 213/12, received CRT/S+CRT 166/59, median radiation dose $45{\pm}13.6Gy$, Median survival 13.5 (11-15), overall survival (OS) One/Two/Three 57/21/16%, Died/alive 158/97, Univariate analysis prognostic factors: age/stag/differentiation/dose of RT/fraction/treatment, Multivariate analysis predictor factor: dose of RT/fraction. Conclusions: Although this treatment offers some possibility for improvement of patients with esophageal cancer, there remains a significant need for development of new drug and new therapeutic approaches that can substantially impact survival.

The oral dose toxicity test and skin irritation test of eco-friendly plasticizer using crude glycerol derived (폐글리세롤을 이용한 친환경 가소제의 경구투여독성 및 피부자극성 시험)

  • Kang, Soo-Jung;Kim, Heeyoung;Park, Sangwon;Sim, Eunyoung;Kim, Jinhwan
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.25 no.3
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    • pp.322-327
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    • 2015
  • Objectives: The major objective of this study is the oral dose toxicity test and skin irritation test of eco-friendly plasticizer using crude glycerol derived from the biodiesel process. Methods: Glyceroldiacetate laurate(GDL) was synthesized from glycerol monolaurat(GML) and acetic acid. The synthesis of the GDL plasticizer was measured with nuclear magnetic resonance spectroscop(NMR) and FT-IR(Fourier Transform Infrared Spectrometer). To provide information on the safety of GDL, we carried out an oral dose toxicity test for GDL in Sprague-Dawley rats. Also, we carried out a skin irritation test for GDL in New Zealand White rabbits. Results: The oral dose toxicity test in Sprague-Dawley rats showed that GDL is a non-toxic material. The result of the skin irritation test on New Zealand White rabbits showed that GDL is non-irritating. Conclusions: From the results of oral dose toxicity test and skin irritation test, we concluded that the developed plasticizer showed excellent eco-friendly property. Based on our results, we confirmed the development of an eco-friendly non-phthalate plasticizer. Applicability for PVC toys and food and drug packaging materials was found.

Similarity Model Analysis and Implementation for Enzyme Reaction Prediction (효소 반응 예측을 위한 유사도 모델 분석 및 구현)

  • Oh, Joo-Seong;Na, Do-Kyun;Park, Chun-Goo;Ceong, Hyi-Thaek
    • The Journal of the Korea institute of electronic communication sciences
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    • v.13 no.3
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    • pp.579-586
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    • 2018
  • With the beginning of the new era of bigdata, information extraction or prediction are an important research area. Here, we present the acquisition of semi-automatically curated large-scale biological database and the prediction of enzyme reaction annotation for analyzing the pharmacological activities of drugs. Because the xenobiotic metabolism of pharmaceutical drugs by cellular enzymes is an important aspect of pharmacology and medicine. In this study, we apply and analyze similarity models to predict bimolecular reactions between human enzymes and their corresponding substrates. Thirteen models select to reflect the characteristics of each cluster in the similarity model. These models compare based on sensitivity and AUC. Among the evaluation models, the Simpson coefficient model showed the best performance in predicting the reactivity between the enzymes. The whole similarity model implement as a web service. The proposed model can respond dynamically to the addition of reaction information, which will contribute to the shortening of new drug development time and cost reduction.

Histological Subtype of Ovarian Cancer as a Determinant of Sensitivity to Formamidine Derivatives of Doxorubicin - in Vitro Comparative Studies with SKOV-3 and ES-2 Cancer Cell Lines

  • Denel-Bobrowska, M.;Lukawska, M;Oszczapowicz, I;Marczak, A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4223-4231
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    • 2016
  • Background: Development of new apoptosis-inducing drugs is a promising trend in anticancer therapy. For this purpose several formamidinoderivatives of doxorubicin were synthesized. The aim of our study was to investigate effects of the five formamidinodoxorubicins in the ES-2 human ovarian clear cell carcinoma line, for comparison with data obtained previously for SKOV-3 human ovarian adenocarcinoma cells, to answer the question of whether and to what extent the histological cell type is a possible determinant of sensitivity to tested anthracyclines. Materials and Methods: In our experimental work the following methods were used: spectrophotometric assays with MTT; fluorimetric assays - double staining with Hoechst 33258 and propidium iodide (PI), measurement of caspase-3, -8, -9 activity, intracellular accumulation of DOX and analogues, estimation of drug uptake, mitochondrial transmembrane potential; flow cytometry - phosphatidylserine (PS) externalization with annexin V-FITC and PI fluorochromes. Results: Effects of the derivatives of doxorubicin were partially linked with the specific type of cancer cell although intracellular accumulation and cellular uptake of DOX and derivatives were similar in both. All of the investigated derivatives were considerably more cytotoxic than DOX. Formamidinodoxorubicins were able to induce caspase-dependent apoptotic cell death in both cell types. Conclusions: All new formamidine derivatives of DOX were able to induce caspase - dependent apoptosis in human ovarian cancer cell lines SKOV-3 and ES-2. Obtained results suggested that formamidine derivatives of DOX may be promising candidates for the prospective chemotherapeutic agents for the two different histological subtypes of ovarian cancer.

Development of Baccillus megaterium Disk Assay Kit for the Determination of Antibacterial Residues in Animal Tissues (식육중 잔류 향균물질의 검출을 위한 Bacillus megaterium 디스크 검사킷트 개발)

  • 손성완;조병훈;진남섭;이혜숙;윤순학;김재학;이재진;이영순
    • Journal of Food Hygiene and Safety
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    • v.11 no.4
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    • pp.315-321
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    • 1996
  • Various antimicrobial drug screen tests have been used in order to ensure food safety. However, the conventional screen tests, the Swab Test on Premises(STOP, USA), the Calf Antibiotic and Sulfa Test(CAST, USA) and the European Economic Community 4-plate Test(FPT, EU) are not sufficiently rapid or sensitive enough to detect low levels of sulfa drugs in meat. We developed a new screen test kit for the determination of the antimicrobial residues in meat called the Bacillus megaterium Disk Assay(BmDA). A comparison of BmDA with the older screen tests showed BmDA was as good as the older ones with several advantages. The new test kit is faster-it can be read in 4∼6 hours instead of 16∼18 hours. Moreover, BmDA can discriminate sulfa drugs from other antimicrobial drugs because p-aminobenzoic acid countacts the inhibiting action of sulfa drugs. Minimum detectable levels of sulfa drugs were significantly improved at the lever of 0.025*0.1 pp, compared with the level of 1.0 ppm in FPT. A comparison of BmDA with the older screen tests in HPLC confirmed meat samples exceeded the Korean tolerance value of 0.1 ppm showed BmDA was the most sensitive in the microbiological screen tests. As the microbiological screen tests have already known, a person familiar with simple laboratory techniques should have no difficulty in using it to detect antimicrobial residues in meat. This would be a simple, economic method of antimicrobial residues detection which might be succesfully used by many laboratories.

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