• Title/Summary/Keyword: therapeutic agents

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Novel Approaches for Efficient Antifungal Drug Action

  • Lee, Heejeong;Lee, Dong Gun
    • Journal of Microbiology and Biotechnology
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    • v.28 no.11
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    • pp.1771-1781
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    • 2018
  • The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

A Study on Cases and Clinical Trials Applying Topical Agents Including Natural Products for Atopic Dermatitis Treatment (천연물 외용제를 적용한 아토피피부염 증례 및 임상 연구 고찰)

  • Gwang-Yeel Seo;Kyuseok Kim
    • Journal of Convergence Korean Medicine
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    • v.2 no.1
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    • pp.35-55
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    • 2021
  • Objectives: To investigate the characteristics of topical agents including natural products using for atopic dermatitis treatment via a review on the cases and clinical trials. Methods: Through a search on Pubmed, EMBASE, Cochrane library, DBPIA, NDSL, and OASIS, we selected papers that applied natural products externally for atopic dermatitis and analyzed them. Results: Finally, Seventeen papers were selected. As the primary outcome, changes in the SCORAD and EASI, were the most used. The most frequent type of external formulation was cream. In terms of the frequency of use, it was used at least twice a day in all studies. When evaluated based on SCORAD, EASI, SH and TEWL, the improvement effect on atopic dermatitis was highest when the ointment formulation and the moisturizer formulation were used. A few side effects of topical agents including natural products were observed, but most were mild symptoms and no serious side effects occurred. Conclusion: This study is meaningful in that it has drawn a significant trend for studies that have been published in the last 5 years that contain a single intervention for topical agents including natural products, and that it presents the direction and evidence for the application of external therapy to increase the therapeutic effect of atopic dermatitis.

Aloe vera Inhibits Proliferation of Human Breast and Cervical Cancer Cells and Acts Synergistically with Cisplatin

  • Hussain, Arif;Sharma, Chhavi;Khan, Saniyah;Shah, Kruti;Haque, Shafiul
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2939-2946
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    • 2015
  • Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies.

Recent Findings on the Mechanism of Cisplatin-Induced Renal Cytotoxicity and Therapeutic Potential of Natural Compounds

  • Lee, Dahae;Choi, Sungyoul;Yamabe, Noriko;Kim, Ki Hyun;Kang, Ki Sung
    • Natural Product Sciences
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    • v.26 no.1
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    • pp.28-49
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    • 2020
  • The efficacy and side effects associated with anticancer drugs have attracted an extensive research focus. Onconephrology is an evolving field of nephrology that deals with the study of kidney diseases in cancer patients. Most renal diseases in cancer patients are unique, and management of renal disease can be challenging especially in the presence of continuing use of the nephrotoxic drugs. Cisplatin is one of the most important chemotherapeutic agents used in the treatment of various malignancies, such as head, neck, ovarian, and cervical cancers. The major limitation in the clinical use of cisplatin is its tendency to induce adverse effects, such as nephrotoxicity. Recently, plant-derived phytochemicals have emerged as novel agents providing protection against cisplatin-induced renal cytotoxicity. Owing to the diversity of phytochemicals, they cover a wide spectrum of therapeutic indications in cancer and inflammation and have been a productive source of lead compounds for the development of novel medications. Of these agents, the effectiveness of triterpenoids, isolated from various medicinal plants, against cisplatin-induced renal cytotoxicity has been reported most frequently compared to other phytochemicals. Triterpenes are one of the most numerous and diverse groups of plant natural products. Triterpenes ameliorate cisplatin-induced renal damage through multiple pathways by inhibiting reactive oxygen species, inflammation, down-regulation of the MAPK, apoptosis, and NF-κB signaling pathways and upregulation of Nrf2-mediated antioxidant defense mechanisms. Here, we reviewed recent findings on the natural compounds with protective potential in cisplatin-induced renal cytotoxicity, provided an overview of the protective effects and mechanisms that have been identified to date, and discussed strategies to reduce renal cytotoxicity induced by anticancer drugs.

NAD(P)H Quinone Oxidoreductase 1 (NQO1) as a Cancer Therapeutic Target (암 치료 표적으로의 NAD(P)H Quinone Oxidoreductase 1 (NQO1))

  • Park, Eun Jung;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.24 no.1
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    • pp.98-103
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    • 2014
  • NAD(P)H quinone oxidoreductase 1 (NQO1) is a flavoprotein that catalyzes the two electron reduction of diverse substrates, including quinones. It uses NADH or NADPH as a cofactor for enzymatic machinery. In the metabolism of quinones, NQO1 has two conflicting functions because of the different stability of converted hydroquinones. The stable form of hydroquinone is excreted from cells by conjugation with glutathione or glucuronic acid. The unstable form of hydroquinone induces cell death by induction of oxidative stress and DNA damage. Certain quinones known as bio-reductive agents have a cytotoxic function following reduction by NQO1. Bio-reductive agents, such as ${\beta}$-lapachone or mitomycin C, induce the depletion of NAD(P)H and the generation of oxidative stress in an NQO1-dependent manner. NQO1 is highly expressed in several cancer tissues. Therefore, NQO1 is a good therapeutic target for cancer treatment with bio-reductive agents.

Technique of Drug Resistance Test of Clinical Value for the Selection of Antibacterial Agents (항균성제제(抗菌性製劑) 선택(選擇)에 있어 내성검사요령(耐性檢査要領)의 임상적응용(臨床的應用))

  • Kim, Kyo Joon;Lee, Hun Jun
    • Korean Journal of Agricultural Science
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    • v.10 no.2
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    • pp.193-199
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    • 1983
  • The authors carried out bovine mastitis test by California Mastitis test (CMT) for the milk from dairy cows in the suburbs of Daejeon. Among the CMT positive milk, Staphylococcus aureus were isolated and, for the proper selection of the commercial antibacterial agents, the strains were tested for the resistant test to the agents. The results obtained were summarized as follows. 1. The resistant test appeared graduate resistance is in such cases continuously repeat with the therapeutic antibacterial agents. 2. The result of resistant test appeared the weakly resistance, untill 4 times subculture in the Rifamastene, Neo-cillin, and 6 times in the Abimasten-100, Neo-masti, Special formular and mastalone. 3. In Tardomycel-L there was rare resistant reactions, untill 6 times subculture. 4. The author recommend that select the antibacterial agents by resistant test and use the selective agents in turn.

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Application of HIV-1 Complementation System to Screen the Anti-AIDS Agents That Targets the Late Stage of HIV-1 Replication Cycle (바이러스 생활환의 후기 단계에 작용하는 항AIDS제의 탐색을 위한 HIV-1 Complementation System의 응용)

  • Ryu, Ji-Yoon;Choi, Soo-Young;Kim, Yung-Hi;Park, Jin-Seu
    • The Journal of Korean Society of Virology
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    • v.30 no.3
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    • pp.161-170
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    • 2000
  • Continuous efforts are being made to find effective therapeutic agents against HIV-1, the causative agents of AIDS. In this study, we developed a cell-based assay system employing a trans-complementation for production of recombinant viruses which are capable of undergoing one round of replication in CD4+ T cells. This assay system was tested for ability to screen the agents that act at late stage of HIV-1 life cycle. The effect of a protease inhibitor on the trans-complementation assay was assessed. Recombinant HIV-1 viruses were prepared from a trans-complementation in the presence of various concentrations of protease inhibitor. Inhibition of single round infection of these recombinant viruses by protease inhibitor was observed to be a dose-dependent manner. Inhibitory effects of a protease inhibitor on HIV-1 Gag polyprotein processing by HIV-1 protease was detected at concentrations of the protease inhibitor compatible with inhibition of virus infection, confirming that the corresponding step was involved in the inhibitory mechanism of this compound. Together, these results provide evidence that a cell-based assay system established in this study can be used to screen the agents that target the late stage of HIV-1 life cycle.

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Validation of Voriconazole Therapeutic Drug Monitoring in Lung Transplant Recipients Receiving Voriconazole alone for Treatment of Invasive Aspergillosis (침습성 아스페르길루스증의 치료 목적으로 voriconazole을 단독으로 투여받는 폐이식 환자에서 voriconazole 약물혈중농도 모니터링의 유효성 검증)

  • Son, Yu Jeong;Lee, Kyung A;Jo, Ju Hee;Kim, Jae Song;Son, Eun Sun;Park, Moo Suk
    • Korean Journal of Clinical Pharmacy
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    • v.29 no.2
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    • pp.89-100
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    • 2019
  • Background: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. Methods: The electronic medical records of lung transplant recipients (${\geq}19$ years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. Results: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. Conclusions: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.

Role of Micronutrients in Skin Health and Function

  • Park, Kyungho
    • Biomolecules & Therapeutics
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    • v.23 no.3
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    • pp.207-217
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    • 2015
  • Skin is the first line of defense for protecting our bodies against external perturbations, including ultraviolet (UV) irradiation, mechanical/chemical stress, and bacterial infection. Nutrition is one of many factors required for the maintenance of overall skin health. An impaired nutritional status alters the structural integrity and biological function of skin, resulting in an abnormal skin barrier. In particular, the importance of micronutrients (such as certain vitamins and minerals) for skin health has been highlighted in cell culture, animal, and clinical studies. These micronutrients are employed not only as active compounds in therapeutic agents for treating certain skin diseases, but also as ingredients in cosmetic products. Here, the author describes the barrier function of the skin and the general nutritional requirements for skin health. The goal of this review is to discuss the potential roles and current knowledge of selected micronutrients in skin health and function.