• Title/Summary/Keyword: active agents

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Pulmonary Resection Combined with Isoniazid-and Rifampin-based Drug Therapy for Patients with Multidrug-resistant Tuberculosis (다제내성 폐결핵 환자에서 폐절제술 후 일차 항결핵제 치료)

  • Park, Seung-Kyu;Kim, Jin-Hee;Kim, Jun-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.2
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    • pp.179-185
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    • 2005
  • Background : To evaluate the clinical efficacy of pulmonary resection combined with first-line antituberculous drug therapy in patients with well-localized, cavities-containing pulmonary multidrug-resistant tuberculosis (MDR-TB). Method : From February 1998, seventeen patients with well-localized, cavities-containing pulmonary MDR-TB were enrolled and followed prospectively up to December 2004. After radical pulmonary resection, the patients were treated with antituberculous drugs comprising of isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) (3HERZS/3HERS/6HER). Results : All recovered isolates of M. tuberculosis were resistant to both isoniazid and rifampin, and to a mean of 4.8 antituberculous drugs (range, 2 to 7 drugs). Surgical procedures included lobectomy (13 patients), lobectomy plus segmentectomy (3 patients), and pneumonectomy (1 patient). The median time for postoperative sputum smear and culture conversion was 2 days (range, 1 to 23 days). Fifteen (94%) patients had durable cures (mean follow-up period, 39.0 months). One patient failed to convert her sputum and was successfully switched to second-line therapy; one patient developed active disease again almost 7 years later, likely due to re-infection with a new M. tuberculosis strain. Conclusion : Radical resection combined with administration of first-line antituberculous agents was effective in patients with well-localized, cavities-containing pulmonary MDR-TB.

Antimutagenic Mechanism of Water Extract from Rehmannia glutinosa Liboshitz on 4-nitroquinoline 1-oxide Induced Mutagenesis n E. coli B.r (대장균에서 4-nitroquinoline 1-oride의 변이원성에 대한 숙지황 물추출물의 항돌연변이 작용특성)

  • 안병용;한종현;최동성
    • KSBB Journal
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    • v.16 no.5
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    • pp.486-492
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    • 2001
  • The antimutagenic mechanism of the fraction III(RG III)separated from the water extract of Rehmannia glutionosa was investigated by Escherichia. coli GW and B/r strains. RG-III treatment did not affect the ${\beta}$-galactosidase activity E. coli GW-1060, 1106, 1107 and 1105. These results indicated that RG-III did not induce RecA protein amplification and did not also prevent the proteolytic cleavage of LexA. The bio-antimutagenicity and survival effect of RG-III on 4-nitroquinoline 1-oxide(4NQO), N-methyl-N-nitor-N\`-nitrosoguanidine(MNING) were investigate by E. coli B/r strains with have different pathway of DNA repai. RG-III slightly increased the survival of 4NQO-treated WP2, WP2s, WP67, CM561, CM611 cells, but the reactivation of survival cannot ve explained by the repair mode. RG-III caused the decrease of mutagenicity and lethality treated with MNNG in ZA159 despite of the increase in WP2, WP2s, WP67, CW561, CM611. Compared with bio-antimutagenic effects of RG-III on 4NQO, greatly increased antimutagenic effects of RG-III were observed with all the E. coli B/r strains tested, but less active in ZA159. These results suggest that RG-III was identified as a blocking agent for preventing the 4NQO induced mutagenesis, and may act as chl-products.

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An engineered PD-1-based and MMP-2/9-oriented fusion protein exerts potent antitumor effects against melanoma

  • Wei, Mulan;Liu, Xujie;Cao, Chunyu;Yang, Jianlin;Lv, Yafeng;Huang, Jiaojiao;Wang, Yanlin;Qin, Ye
    • BMB Reports
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    • v.51 no.11
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    • pp.572-577
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    • 2018
  • Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

Recent Natural Products Involved in the Positive Modulation of Melanogenesis (Melanogenesis 양성적 조절 에 관여하는 최근 천연물의 동향)

  • Kim, Moon-Moo
    • Journal of Life Science
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    • v.28 no.6
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    • pp.745-752
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    • 2018
  • Melanogenesis is involved in the pigmentation of the hair, eyes, and skin in living organisms. Various signaling pathways stimulated by ${\alpha}-MSH$, SCF/c-Kit, $Wnt/{\beta}-catenin$, nitric oxide and ultraviolet activate melanocyte, leading to melanin production by tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 expressed via the microphthalmia-associated transcription factor (MITF). However, the abnormal regulation of melanogenesis causes dermatological issues such as graying hair and vitiligo. Therefore, the activators that promote melanogenesis are crucial for the prevention of graying hair and the treatment of hypopigmentary disorders. Many melanogenesis stimulators have been studied for the development of novel drugs derived from synthesized compounds and natural products. Here, in addition to providing a description of a common signaling pathway in the melanogenesis of graying hair and the vitiligo process for the development of novel anti-hair graying agents, this article reviews natural herbs and the active ingredients that promote melanin synthesis as a pharmaceutical agent for the treatment of vitiligo. In particular, compounds such as Imatinib and Sugen with a stimulating effect on melanogenesis as a side effect of the drugs, are also introduced. Recent advances in research on natural plant extracts such as Polygonum multiflorum, Rhynchosia Nulubilis, Black oryzasativa, and Orysa sartiva, widely known as traditional and medicinal extracts, are also reviewed.

Improved Antibacterial Effect of Blending Essential Oils (블렌딩 에센션오일의 항균효과 증진)

  • Kwon, Pil Seung;Kim, Dae-Jung;Park, Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.3
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    • pp.256-262
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    • 2017
  • Essential oil from herb is known to exert pharmacological effects on the human body. In this study we investigated the antibacterial activity of 4 essential oils (teetree, rosemary, melisa, and lavender), as well as the blended mixture oil of teetree, rosemary, and melisa (TRM) on three bacteria, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Antibacterial analysis was performed using the standard disk diffusion method, and minimum inhibition concentration was determined by the broth microdilution method with different concentrations of essential oils (0.5, 1, 2 and 3 mg/mL). After incubation at $37^{\circ}C$ for 24 h, the antibacterial activity was assessed by measuring the zone of growth inhibition surrounding the disks. Herb oil with the inhibition zones showed varied values ranging from6 to 25 mm. However, the components of herb oil of TRM are as highly active as the teetree oil against pathogens, generating large inhibition zones for both gram negative and positive bacteria (13~22 mm and 8 mm inhibition zones). In the analysis for MIC, TRM showed growth-inhibitory effects at 0.0625% for S. aureus and E. coli, and 1.25% for P. aeruginosa. This result demonstrated that the anti-microbial activity of TRM was greater than a single herb oil, including oxacillin, rosemary, and teetrea. As a single herb oil, both rosemary and teetrea also had an anti-microbial effect by itself, and we can expect that the blended oil mixture may exert a synergistic effect against multidrug resistant bacteria, suggesting its future application in natural preservative agents for health food and cosmetics.

D99 Type I Signal Peptidase Implicated Stabilizing the Protein Structure (Type I 신호펩디드 가수분해효소에 존재하는 D99 아미노산 잔기의 구조적 역할 가능성)

  • Sung, Meesook;Eunyoung Han;Lee, Hoyoung
    • Microbiology and Biotechnology Letters
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    • v.31 no.2
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    • pp.140-144
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    • 2003
  • Type Ⅰ signal peptidase is an integral membrane protein that functions to cleave signal peptides from secreted and membrane proteins. The enzyme serves as a potential target for the development of novel antibacterial agents due to its unique physiological properties. Despite being one of the best characterized enzymes, the catalysis of Type Ⅰ signal peptidase still remains controversy over the catalytic serine/lysine dyad mechanism. It appears that the dyad proteases are generally less efficient than the prototypical serine/histidine/aspartic acid triad found in most enzymes, although Type Ⅰ signal peptidase is an exception to this rule. In this paper, we have proposed that Type Ⅰ signal peptidase may act as the serine/lysine/aspartic acid triad cataltytic mechanism. Therefore, the aspartic acid 99 residue in the E. coli signal peptidase was chosen and mutated to an alanine to see if there is any possible role of the aspartic acid in the catalytic function. Type Ⅰ signal peptidase D99A protein was inactive in vitro assay using the procoat synthesized by in vitro transcription translation. However, the mutant was active using a highly sensitive in vivo assay. Pulse-chase experiments show that the replacement of aspartic acid 99 with alanine results in a very unstable signal peptidase molecule. Therefore, we conclude that it is unlikely that the residue is directly involved in catalysis, but rather plays an important role in stabilizing the protein structure.

Moisturizing and Anti-oxidation Effect of Astragalus membranaceus Root Extract (황기추출물의 보습 및 항산화 효과)

  • Jung, Taek-Kyu;Kim, Mi-Jin;Lim, Kyung-Ran;Yoon, Kyung-Sup
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.3 s.58
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    • pp.193-200
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    • 2006
  • We investigated the effect of moisturizing and anti-oxidation of Astragalus membranaceus (Astragali Radix) root extract with respective to growing districts and extract methods for the purpose of development of cosmetic ingredients. Astragalii Radix was collected in Jecheon, Jeongseon, Taebaek, and Yeongju in Korea and China as growing districts. Formononetin was determinated by HPLC method as one of the various active agents in Astragalus membranaceus root extract. The 75% ethanol extract demonstrated to be more effective than $H_2O$-extracted one for a scavenging activities to DPPH radicals and reactive oxygens. The 75% ethanol extract showed $IC_{50}$ (50% scavenging concentration) of 2.162 mg/mL and 2.981 mg/mL in case of free radical scavenging activity test and reactive oxygen scavenging activity test, respectively Especially, free radical scavenging activity of isoflavonoids isolated from ethylacetate fraction was similar to scavenging activity of genistein. Astragalus membranaceus root extract of Jecheon district by sonicating extraction method was more effective in skin hydration compared with others.

The Effect of Antibacteria and Antioxidantion Activities from Needle Leaf Tree (침엽수 추출물의 항균.항산화 효과)

  • Zhoh, Choon-Koo;Kim, Kyung-Rae;Kim, Joo-Chan
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.4
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    • pp.269-273
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    • 2007
  • We studied anti-microbial and anti-oxidant activities of bio-active components in stem of Juniperus chinensis L. and leaf of Abies koreana Wilson. Those plants of needle leaf tree family were reported to contain anti-cancer compounds. The anti-bacterial activity was tested by Broth dilution method against Escherichia coli and Staphylococcus aureus. As results, Juniperus chinensis L. and Abies koreana Wilson extracts showed 17.0% and 8.5% higher anti-bacterial activity than methyl paraben, respectively. The free radical scavenging activity of Juniperus chinensis L. and Abies koreana Wilson extracts showed 45 % and 44 % at 5,000 ppm. We measured polyphenol (catechin equivalent) and flavonoids quantity. The Juniperus chinensis L. extract contained 312 mg/g of polyphenol and 105 mg/g of flavonoids. The Abies koreana Wilson extract contained 280 mg/g of polyphenol and 103.8 mg/g of flavonoids. The cytotoxicity of extracts was measured by neutral red assay. Extracts did not affect the viability of CCK-986sk cells up to a concentration of 1,250 ppm. In conclusion, these data suggest that extracts of needle leaf trees would be usefull as antiseptic agents and anti-oxidants for cosmetic products.

Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain

  • Kim, Min Kyoung;Kang, Hyun;Baek, Chong Wha;Jung, Yong Hun;Woo, Young Cheol;Choi, Geun Joo;Shin, Hwa Yong;Kim, Kyung Soo
    • Journal of Ginseng Research
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    • v.42 no.2
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    • pp.183-191
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    • 2018
  • Background: Ginseng saponin has long been used as a traditional Asian medicine and is known to be effective in treating various kinds of pain. Ginsenoside Rf is one of the biologically active saponins found in ginseng. We evaluated ginsenoside Rf's antinociceptive and anti-inflammatory effects, and its mechanism of action on adrenergic and serotonergic receptors, in an incisional pain model. Methods: Mechanical hyperalgesia was induced via plantar incision in rats followed by intraperitoneal administration of increasing doses of ginsenoside Rf (vehicle, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2 mg/kg). The antinociceptive effect was also compared in a Positive Control Group that received a ketorolac (30 mg/kg) injection, and the $Na{\ddot{i}}ve$ Group, which did not undergo incision. To evaluate the mechanism of action, rats were treated with prazosin (1 mg/kg), yohimbine (2 mg/kg), or ketanserin (1 mg/kg) prior to receiving ginsenoside Rf (1.5 mg/kg). The mechanical withdrawal threshold was measured using von Frey filaments at various time points before and after ginsenoside Rf administration. To evaluate the anti-inflammatory effect, serum interleukin $(IL)-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels were measured. Results: Ginsenoside Rf increased the mechanical withdrawal threshold significantly, with a curvilinear dose-response curve peaking at 1.5 mg/kg. $IL-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels significantly decreased after ginsenoside Rf treatment. Ginsenoside Rf's antinociceptive effect was reduced by yohimbine, but potentiated by prazosin and ketanserin. Conclusion: Intraperitoneal ginsenoside Rf has an antinociceptive effect peaking at a dose of 1.5 mg/kg. Anti-inflammatory effects were also detected.

Compound K improves skin barrier function by increasing SPINK5 expression

  • Park, No-June;Bong, Sim-Kyu;Lee, Sullim;Jung, Yujung;Jegal, Hyun;Kim, Jinchul;Kim, Si-Kwan;Kim, Yong Kee;Kim, Su-Nam
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.799-807
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    • 2020
  • Background: The skin acts as a barrier to protect organisms against harmful exogenous agents. Compound K (CK) is an active metabolite of ginsenoside Rb1, Rb2 and Rc, and researchers have focused on its skin protective efficacy. In this study, we hypothesized that increased expression of the serine protease inhibitor Kazal type-5 (SPINK5) may improve skin barrier function. Methods: We screened several ginsenosides to increase SPINK5 gene promoter activity using a transactivation assay and found that CK can increase SPINK5 expression. To investigate the protective effect of CK on the skin barrier, RT-PCR and Western blotting were performed to investigate the expression levels of SPINK5, kallikrein 5 (KLK5), KLK7 and PAR2 in UVB-irradiated HaCaT cells. Measurement of transepidermal water loss (TEWL) and histological changes associated with the skin barrier were performed in a UVB-irradiated mouse model and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like model. Results: CK treatment increased the expression of SPINK5 and decreased the expression of its downstream genes, such as KLKs and PAR2. In the UVB-irradiated mouse model and the DNCB-induced atopic dermatitis model, CK restored increased TEWL and decreased hydration and epidermal hyperplasia. In addition, CK normalized the reduced SPINK5 expression caused by UVB or DNCB, thereby restoring the expression of the proteins involved in desquamation to a level similar to normal. Conclusions: Our data showed that CK contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases.