• Title/Summary/Keyword: gerontology

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Mechanism of Panax notoginseng saponins modulation of miR-214-3p/NR1I3 affecting the pharmacodynamics and pharmacokinetics of warfarin

  • Yuting Yang;Zhenyu Zhai;Huiming Yao;Ling He;Jun Shao;Zirong Xia;Juxiang Li
    • Journal of Ginseng Research
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    • v.48 no.5
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    • pp.494-503
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    • 2024
  • Background: With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax notoginseng saponins (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism. Methods: The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague-Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3. Results: PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3'-UTR and significantly downregulated NR1I3 expression. Conclusion: Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.

Immunological mechanism of Aging : T & B cell changes (면역학적 노화 기전에 관한 연구: T 및 B 세포의 변화)

  • Kim, Jay Sik;Lee, Won Kil;Suh, Jang Soo;Song, Kyung Eun;Lee, Joong Won;Lee, Nan Young;Weksler, Marc E.
    • IMMUNE NETWORK
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    • v.1 no.3
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    • pp.236-243
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    • 2001
  • Background: An immunological approach for aging mechanism appears to be important. Lymphocyte subsets analysis in peripheral blood is widely performed to assess the immune status and to diagnose and monitor various diseases. Some lymphocyte subsets are known to change with age, but only few data about age-related reference ragnes for these subsets in healthy individuals have been reported. So we attempted to report reference ranges for these subsets in each age group and review changes of the results with age for the secondary studies about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement (VDJ) including recombination activating genes (RAG-1 and RAG-2). Methods: Lymphocyte subset analysis was performed on 302 subjects, 189 males and 113 females with age group of all decades of life. Two color direct immunofluorescene flow cytometry (FCM) was done using $Simultest^{TM}$ IMK-Lymphocyte kit (Becton Dickinson, USA), $FACScan^{TM}$ (Becton Dickinson, USA) and $FACSCalibur^{TM}$ (Becton Dickinson, USA). Lymphocyte subsets analysed were T ($CD3^+$) and B cells ($CD19^+$), helper/inducer T ($CD4^+$) and suppressor/cytotoxic T cells ($CD8^+$), helper/suppressor ($CD4^+/CD8^+$) ratio and natural killer (NK) cells ($CD3^-CD16^+/CD56^+$). The absolute numbers of each subset were calculated from total lymphocyte counts. Data collected was analysed using SAS 6.12. A P-value of < 0.05 was considered significant. Results: We reported the counts and percentages of lymphocyte and these subsets in each age group. There were no statistically significant differences between male and female subjects. The percentage of $CD4^+$ T cells, and the count of NK cells did not show the significant difference among the various age groups. The age-related changes observed in our study were as following: 1) a decrease in the percentages of T cells, B cells and $CD8^+$ T cells ; 2) a decrease in the counts of B cells and $CD8^+$ T cells ; 3) an increase in the percentage and count of NK cells ; and 4) an increase in the $CD4^+/CD8^+$ ratio. Conclusion: The characteristics of aging process appeared to be showing a marked decrease of lympocyte subsets T and B cells as well as T8 ($CD8^+$). The age-related increase of the percentage of cells bearing NK marker can be interpreted as a compensatory consequence to cope with the decrease of T cells related to the thymic involution. These changes with age appeared to be for the secondary study about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement.

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Research Trend of the Healthcare and Medical Care for Elders in the Journal of the Korea Gerontological Society (한국노년학의 보건·의료·건강영역 연구동향)

  • Kim, Hyun Sook;Park, Yeon-Hwan;Kim, Young Sun
    • 한국노년학
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    • v.38 no.3
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    • pp.705-723
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    • 2018
  • In this study we review the selected articles on elderly health and medical care published in the Journal of the Korea Gerontological Society (JKGS) in the last 40 years, and make suggestions for future research directions for gerontological health and medical care issues. Of all the 40 year publications from volume 1 (1980) to 38 (2017), we first examined the 30th anniversary review on the subject of gerontological nursing care and healthcare policies published in JKGS from 1980 (vol. 1, No. 1) to 2008 (vol. 28, No. 2), and reviewed recent 237 researches of this decade (out of all 655 articles from 2008, vol. 28, No. 3 to 2017, vol. 38, No. 4). We could find the following trends. Firstly, the analysis of the primary authors in the past 10 years revealed that those in public health, nursing and other health-related including physical education areas have dealt the subjects focusing on physical health while those in social welfare mostly on mental health. That is, physical health has been the prime subject of researches in the health and medical care area. Secondly, in the same period quantitative researches were accounted for 89.9%, which is similar to the trend of the first 30 years 81.5 %. On the other hand, qualitative studies were only 11 cases and the focus group interview were the most frequently used method comprising 33.3% among them. Thirdly, the non-experimental researches in the past 10 years comprise 65.4%, which was 82.7% in 1980 2008 period, indicating the increasing trend in experimental researches to deal with the issues in medical and healthcare fields. Lastly, the subjects of the researches were mostly the elders who are healthy, residents of city areas, or home dwellers, and 60% of them were over 65 years old in the past 10 years while the proportion was 42.7% in the previous review period. 81.6 % of the researches in the past 10 years was dealing both genders, slightly decreased trend compared to 88.5% of the previous review period. This study reveals that the researches in non-experimental physical health remains the main stream of JKGS despite the efforts by some researchers to diversify the methods and subjects. Systematic and in-depth researches employing multidisciplinary, qualitative, longitudinal and meta-analytical approaches are called for to guide the gerontolgical health issues with preventive and proactive perspectives.