• Title/Summary/Keyword: HIV(human immunodeficiency virus)

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Nanotechnology in reproductive medicine: Opportunities for clinical translation

  • Shandilya, Ruchita;Pathak, Neelam;Lohiya, Nirmal Kumar;Sharma, Radhey Shyam;Mishra, Pradyumna Kumar
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.4
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    • pp.245-262
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    • 2020
  • In recent years, nanotechnology has revolutionized global healthcare and has been predicted to exert a remarkable effect on clinical medicine. In this context, the clinical use of nanomaterials for cancer diagnosis, fertility preservation, and the management of infertility and other pathologies linked to pubertal development, menopause, sexually transmitted infections, and HIV (human immunodeficiency virus) has substantial promise to fill the existing lacunae in reproductive healthcare. Of late, a number of clinical trials involving the use of nanoparticles for the early detection of reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics have been conducted. However, most of these trials of nanoengineering are still at a nascent stage, and better synergy between pharmaceutics, chemistry, and cutting-edge molecular sciences is needed for effective translation of these interventions from bench to bedside. To bridge the gap between translational outcome and product development, strategic partnerships with the insight and ability to anticipate challenges, as well as an indepth understanding of the molecular pathways involved, are highly essential. Such amalgamations would overcome the regulatory gauntlet and technical hurdles, thereby facilitating the effective clinical translation of these nano-based tools and technologies. The present review comprehensively focuses on emerging applications of nanotechnology, which holds enormous promise for improved therapeutics and early diagnosis of various human reproductive tract diseases and conditions.

Selenium and Human Health : from the view of anticarcinogenic effects (셀레늄과 인간의 건강 : 항암효과를 중심으로)

  • Kim, W.Y.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.4 no.1
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    • pp.89-109
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    • 2002
  • 필수 미량원소인 셀레늄은 인간의 건강에 기본적으로 중요한 역할을 하는 물질이다. 항산화 관여 효소의 작용과 구조역할을 담당하는 셀레늄이 함유된 단백질(selenoproteins)은 항산화 기능이 있을 뿐만 아니라, 갑상선호르몬의 활성화에 관여하는 것으로 밝혀졌다. 또한, 셀레늄은 정상적인 면역체계의 유지에 필요하며, HIV(human immunodeficiency virus)가 진행되어 AIDS로 발전되는 것을 억제하는 작용이 있다는 사실도 밝혀지고 있으며, 정자의 생성과 운동성에 관계하기도 한다. 우울증 환자가 셀레늄을 섭취하게 되면 효과가 있으며, 셀레늄이 순환계질환의 발생을 억제하는 것으로 알려지고 있다. 특히 최근에는 셀레늄의 섭취가 암발생을 예방할 수 있다는 역학조사결과를 토대로, 대규모 셀레늄 임상실험이 다국적 연구의 형태로 2개의 프로젝트(PRECISE, SELECT)가 수행 중이다. 한편, 셀레늄의 항암효과에 대한 세포수준에서의 연구가 활발하게 이루어지고 있으며, 어느 정도 가시적인 결과를 보이고 있다. 따라서, 셀레늄에 대한 재평가가 우리 나라에서도 이루어져야 한다. 그러기 위해서는 지역별로 셀레늄의 정확한 섭취량조차도 파악되어 있지 않을 뿐만 아니라 일일권장량 값조차 정확하지 않은 현실을 볼 때, 셀레늄의 기본적 연구에 대한 관심을 가져야 할 때라고 판단된다.

Determination of N-nitrosodimethylamine in zidovudine using high performance liquid chromatography-tandem mass spectrometry

  • Yujin Lim;Aelim Kim;Yong-Moon Lee;Hwangeui Cho
    • Analytical Science and Technology
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    • v.36 no.6
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    • pp.281-290
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    • 2023
  • Zidovudine is an antiretroviral agent prescribed for the prevention and treatment of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). It is typically recommended to be used in combination with other antiretroviral drugs. Zidovudine has the potential to generate N-nitrosodimethylamine (NDMA) in the presence of dimethylamine and nitrite salt under acidic reaction conditions during the drug manufacturing process. NDMA is a potent human carcinogen that may be detected in drug substances or drug products. An analytical method was developed to determine NDMA in pharmaceuticals including zidovudine using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The analysis involved reversed-phase chromatography on a Kinetex F5 column with a mobile phase comprising water-acetonitrile mixtures. The detection of positively charged ions was conducted using atmospheric pressure chemical ionization (APCI). The calibration curve demonstrated excellent linearity (r = 0.9997) across the range of 1-50 ng/mL with a highly sensitive limit of detection (LOD) at 0.3 ng/mL. The developed method underwent thorough validation for specificity, linearity, accuracy, precision, robustness, and system suitability. This sensitive and specific analytical method was applied for detecting NDMA in zidovudine drug substance and its formulation currently available in the market, indicating its suitability for drug quality management purposes.

Examination of specific binding activity of aptamer RNAs to the HIV-NC by using a cell-based in vivo assay for protein-RNA interaction

  • Jeong, Yu-Young;Kim, Seon-Hee;Jang, Soo-In;You, Ji-Chang
    • BMB Reports
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    • v.41 no.7
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    • pp.511-515
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    • 2008
  • The nucleocapsid (NC) protein of the Human Immunodeficiency Virus-1 plays a key role in viral genomic packaging by specifically recognizing the Psi($\Psi$) RNA sequence within the HIV-1 genome RNA. Recently, a novel cell-based assay was developed to probe the specific interactions in vivo between the NC and $\Psi$-RNA using E.coli cells (J. Virol. 81: 6151-55, 2007). In order to examine the extendibility of this cell-based assay to RNAs other than $\Psi$-RNA, this study tested the RNA aptamers isolated in vitro using the SELEX method, but whose specific binding ability to NC in a living cellular environment has not been established. The results demonstrate for the first time that each of those aptamer RNAs can bind specifically to NC in a NC zinc finger motif dependent manner within the cell. This confirms that the cell-based assay developed for NC-$\Psi$interaction can be further extended and applied to NC-binding RNAs other than $\Psi$-RNA.

Impact of HIV-1 subtypes on gross deletion in the nef gene after Korean Red Ginseng treatment

  • Cho, Young-Keol;Kim, Jung-Eun;Lee, Jinny
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.731-737
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    • 2022
  • Background: The number of primary human immunodeficiency virus (HIV)-1 non-B subtype infections (non-B) and that of reports regarding the differences in the pathogenesis of subtype B and non-B infections are increasing. However, to the best of our knowledge, there have been no reports on gross deletion in the nef gene (g∆nef) in non-B infections. Methods: To determine whether there is a difference in the change in CD4+ T cells after treatment with Korean Red Ginseng (KRG) between patients with subtype B and non-B infections, we retrospectively analyzed and compared the annual decrease in CD4+ T cells (AD) and the proportion of g∆nef in 77 patients who were followed for more than 10 years in the absence of combination antiretroviral therapy. Results: Overall, AD was significantly faster in patients with non-B infections than in those with subtype B infections. Survival analysis showed that the survival probability was significantly higher in subtype B than in non B-infected patients. These differences mainly resulted from significant differences in the amount of KRG and age. In the patients treated with KRG, there was a significant correlation between the amount of KRG and the AD in both subtypes. Interestingly, there was a significant correlation between the amount of KRG and the proportion of g∆nef in patients infected with subtype B, but not in those infected with non-B. The same phenomenon was observed when the KRG dose was adjusted. Conclusion: Our results suggest that non-B may be biologically more stable than subtype B.

Association of HIV infection with MICA(MHC class I chain-related A) gene alleles (HIV감염과 MICA (MHC class I chain-related A) 대립 유전자의 연관성)

  • Kang, Moon-Won;Wie, Seong-Heon;Kim, Yang-Ree;Lee, Joo-Shil;Pyo, Chul-Woo;Han, Hoon;Kim, Tai-Gyu
    • IMMUNE NETWORK
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    • v.1 no.2
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    • pp.135-142
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    • 2001
  • Background: A large number of diseases occur in association with specific HLA-B or-C alleles. Recently a new gene, termed maj or histocompatibility complex class I chain-related gene A (MICA), has been identified in close proximity to HLA-B. The function of this gene is still unknown. However, it is structurally similar to HLA class I genes. MICA gene is polymorphic and is potentially associated with several diseases. Methods: To evaluate the association of MICA gene in Korean patients with human immunodeficiency virus 1 (HIV-1) infections, Polymerase chain reaction-Sequence specific primer (PCR-SSP) was done for MICA alleles in the extracellular exons, and a microsatellite analysis for GCT repeat polymorphisms in the TM exon was also completed. Results: In 199 Korean healthy controls, 7 alleles were observed and the frequencies for each allele were MICA008 (44.7%), MICA0 10 (34.2%), MICA002 (31.7%), MICA004 (23.6%), MICA0 12 (2 1.6%), MICA009 (19.6%), and MICA007 (6.5%). When 65 HIV seropositive patients were analyzed, MICA007 allele frequency was significantly higher than in controls (15.4% vs 6.5 %, RR=2.6, p<0.04). In contrast, the frequencies of other MICA alleles and microsatellite alleles in the transmembrane region of MICA gene were not significantly different between HIV seropositive patients and controls. The tight linkage between MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon was observed as follows; MICA002/A9, MICA004/A6, MICA007/A4, MICA008/A5.1, MICA0 10/A5, and MICA0 12/A4 in both groups. No significant difference between patients and controls was observed in the haplotype frequencies of MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon. Conclusion: The data suggest that immune functions related with MICA gene may affect a HIV infections.

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A DPL (DNA/peptide/liposomes) Tripartite Complex Effective for Transfection in Serum

  • Kim Young-Cheol;Park Jong-Gu
    • Biomedical Science Letters
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    • v.10 no.3
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    • pp.187-194
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    • 2004
  • A short peptide corresponding to the nuclear localization signal (NLS) of human immunodeficiency virus (HIV)-l Tat protein, Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg, was employed to improve the efficiency of cellular uptake of nucleic acids. The peptide was first mixed with a reporter plasmid and then with cationic liposomes to form a tripartite complex of DNA/peptide/liposomes (DPL). Transfection efficiency of the DPL complex was compared with that of the conventional DNA/liposomes (DL) complex. When the DPL complex was formed with various cationic liposomes, DOTAP/DOPE (DP) liposome exhibited superior transfection efficiency to other liposomes tested in vitro. With the inclusion of the peptide, the DPL complex showed much enhanced transfection in various cancer cell lines. Particularly, transfection of the DPL complex in serum increased cellular uptake of a transgene up to 2 fold when compared with that in a serum free condition. Further, when the DPL complex was infused through the ureteric route of a rat, transfection efficiency was shown to be better in reporter gene expression than that obtained with the DL complex. This study shows that the DPL complex that is easy to formulate can be employed for much enhanced cellular uptake of a trans gene.

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Mechanism of T cell exhaustion in a chronic environment

  • Jin, Hyun-Tak;Jeong, Yun-Hee;Park, Hyo-Jin;Ha, Sang-Jun
    • BMB Reports
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    • v.44 no.4
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    • pp.217-231
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    • 2011
  • T cell exhaustion develops under conditions of antigen-persistence caused by infection with various chronic pathogens, such as human immunodeficiency virus (HIV) and myco-bacterium tuberculosis (TB), or by the development of cancer. T cell exhaustion is characterized by stepwise and progressive loss of T cell function, which is probably the main reason for the failed immunological control of chronic pathogens and cancers. Recent observations have detailed some of the intrinsic and extrinsic factors that influence the severity of T cell exhaustion. Duration and magnitude of antigenic activation of T cells might be associated with up-regulation of inhibitory receptors, which is a major intrinsic factor of T cell exhaustion. Extrinsic factors might include the production of suppressive cytokines, T cell priming by either non-professional antigenpresenting cells (APCs) or tolerogenic dendritic cells (DCs), and alteration of regulatory T (Treg) cells. Further investigation of the cellular and molecular processes behind the development of T cell exhaustion can reveal therapeutic targets and strategies for the treatment of chronic infections and cancers. Here, we report the properties and the mechanisms of T cell exhaustion in a chronic environment.

Isolation and structure elucidation of antifungal compounds from the antarctic lichens, Stereocaulon alpinum and Sphaerophorus globosus

  • Kim, Young-Shin;Lim, Chi-Hwan
    • Korean Journal of Agricultural Science
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    • v.47 no.1
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    • pp.183-191
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    • 2020
  • Lichens are composite organisms consisting of a symbiotic association of a fungus with a photosynthetic partner (the photobiont or phycobiont), usually either a green alga or cyanobacterium. According to more recent studies, the biological activities of lichens and lichen substances include an antibiotic activity, antitumor and antimutagenic activity against human immunodeficiency virus (HIV), allergenic activity, plant growth inhibitory activity, and enzyme inhibitory activity. This study screened lichen extracts with a potent in vitro antifungal activity against plant diseases caused by phytopathogenic fungi. The compounds were isolated from Stereocaulon alpinum and Sphaerophorus globosus, and their chemical structures were identified as methyl hematommate, methyl β-orsellinate, 5-hydroxyferulic acid, sphaerophorin, and 2-heptyl-4,6-dimethoxybenzoic acid by electron ionization mass spectrometry (EI-MS) and nuclear magnetic resonance (NMR) spectral analyses. In vitro disease control against Alternaria mali, Cochliobolus miyabeanus, Colletotrium gloeosporioides, and Verticillum dahliae was evaluated. And among the five compounds, only methyl hematommate was effective against A. mali, C. miyabeanus, and C. gloeosporioides. The compounds were isolated from these lichens, which have a similar biosynthetic pathway, respectively. This is the first report of these compounds being isolated from these lichens.

A Case of Disseminated Cutaneous Cryptococcosis Accompanied by Pulmonary Tuberculosis (폐 결핵과 동반된 파종성 피부 크립토콕쿠스증 1예)

  • Choi, Hae Jin;Lee, Sang Hwa;Lee, Tae Hoon;Yoo, Kwang Ha;Lee, Kye Young;Kim, Sun Jong
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.6
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    • pp.527-531
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    • 2008
  • Although disseminated cryptococcosis occurs most commonly in immunocompromised patients, particularly those with a human immunodeficiency virus (HIV) infection, it can occur in immune competent persons. There are no case reports of disseminated cutaneous crytpcoccosis associated with pulmonary tuberculosis in Korea. A 71-year-old female presented with fever and multiple cutaneous nodules. She was finally diagnosed with disseminated cutaneous cryptococcosis accompanied by pulmonary tuberculosis, and was treated successfully with anti-tuberculous medication and fluconazole. She had no apparent predisposing conditions for systemic cryptococcosis. We report this case with a review of the relevant literature.