• 제목/요약/키워드: therapeutic resistance

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Ginsenosides for the treatment of insulin resistance and diabetes: Therapeutic perspectives and mechanistic insights

  • Tae Hyun Kim
    • Journal of Ginseng Research
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    • 제48권3호
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    • pp.276-285
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    • 2024
  • Diabetes mellitus (DM) is a systemic disorder of energy metabolism characterized by a sustained elevation of blood glucose in conjunction with impaired insulin action in multiple peripheral tissues (i.e., insulin resistance). Although extensive research has been conducted to identify therapeutic targets for the treatment of DM, its global prevalence and associated mortailty rates are still increasing, possibly because of challenges related to long-term adherence, limited efficacy, and undesirable side effects of currently available medications, implying an urgent need to develop effective and safe pharmacotherapies for DM. Phytochemicals have recently drawn attention as novel pharmacotherapies for DM based on their clinical relevance, therapeutic efficacy, and safety. Ginsenosides, pharmacologically active ingredients primarily found in ginseng, have long been used as adjuvants to traditional medications in Asian countries and have been reported to exert promising therapeutic efficacy in various metabolic diseases, including hyperglycemia and diabetes. This review summarizes the current pharmacological effects of ginsenosides and their mechanistic insights for the treatment of insulin resistance and DM, providing comprehensive perspectives for the development of novel strategies to treat DM and related metabolic complications.

Responsiveness of Gait Speed to Physical Exercise Interventions in At-risk Older Adults: A Systematic Review and Meta-Analysis

  • Lim, Jaehyun;Lim, Jae Young
    • Annals of Geriatric Medicine and Research
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    • 제21권1호
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    • pp.17-23
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    • 2017
  • Background: In at-risk older adults, gait speed is an important factor associated with quality of life and falling risk. In this study, we assessed whether therapeutic exercise could improve gait speed. Methods: We conducted a meta-analysis to evaluate the 'best' therapeutic exercise method by analyzing each exercise in terms of intensity, type, and several gait speed indices. For the analysis, we gathered 122 papers through a database search and selected 9 (n=627) that were appropriate for the meta-analysis. Results: In 8 of the 9 included papers, gait speed improved with therapeutic exercise. Usual gait speed (n=246) improved more than maximal gait speed (n=574). A resistance program was more effective than a nonresistance program for improving maximal, but not usual, gait speed. We also found that the effects of therapeutic exercise were greater in noncommunity than in community-dwelling elderly people. Conclusion: In conclusion, therapeutic exercise was effective in improving gait speed.

Tamoxifen Resistance in Breast Cancer

  • Chang, Min-Sun
    • Biomolecules & Therapeutics
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    • 제20권3호
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    • pp.256-267
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    • 2012
  • Tamoxifen is a central component of the treatment of estrogen receptor (ER)-positive breast cancer as a partial agonist of ER. It has been clinically used for the last 30 years and is currently available as a chemopreventive agent in women with high risk for breast cancer. The most challenging issue with tamoxifen use is the development of resistance in an initially responsive breast tumor. This review summarizes the roles of ER as the therapeutic target of tamoxifen in cancer treatment, clinical values and issues of tamoxifen use, and molecular mechanisms of tamoxifen resistance. Emerging knowledge on the molecular mechanisms of tamoxifen resistance will provide insight into the design of regimens to overcome tamoxifen resistance and discovery of novel therapeutic agents with a decreased chance of developing resistance as well as establishing more efficient treatment strategies.

저항운동치료 처방에 관한 연구 (A Study of Resistive Therapeutic Exercise Prescription)

  • 배성수;김태숙;김은주
    • The Journal of Korean Physical Therapy
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    • 제11권1호
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    • pp.149-156
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    • 1999
  • Resistive therapeutic exercise prescription goal is to improve functional performance and capabilities through the development of increased muscular strengh endurance or power. Resistance can be applied to either dynamic or static muscle contractions. Resistive therapeutic exorcise can be carried nut concentrically, eccentrically, isometrically, isokinetically. Neurodevelopmental treatment has not resistive therapeutic exercise concept. But proprioceptive neuromuscular facilitate techniques have resistive therapeutic exercise concept with pattens and techniques. It is aid muscle contraction, motor control and increase strength. Manual muscle testing will help the therapist establish a qualitative and quantitative baseline level of strength. Manual resistance maybe applied a against controlled lengthening contraction re static contraction of a muscle. A repetition maximum is not easy to calculate and is not the most accurate method available today to measure strength before of after a resistive therapeutic exercise program. Oddvar Holten Diagram is essy to calculate and is the most accurate method available today to measure strength before of after a resistive therapeutic exercise program. Plyometric training emphasize the development of muscular power and coordination. Quick bursts of force in functional movement patterns are often necessary of a patient is to return to high-demand occupational, recreational or sports related activities.

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Assessment of Risks and Benefits of Using Antibiotics Resistance Genes in Mesenchymal Stem Cell-Based Ex-Vivo Therapy

  • Narayan Bashyal;Young Jun Lee;Jin-Hwa Jung;Min Gyeong Kim;Kwang-Wook Lee;Woo Sup Hwang;Sung-Soo Kim;Da-Young Chang;Haeyoung, Suh-Kim
    • International Journal of Stem Cells
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    • 제16권4호
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    • pp.438-447
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    • 2023
  • Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant E. coli (E. coli/PuroR) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli/PuroR. In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.

Butein Disrupts Hsp90's Molecular Chaperoning Function and Exhibits Anti-proliferative Effects Against Drug-resistant Cancer Cells

  • Seo, Young Ho
    • Bulletin of the Korean Chemical Society
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    • 제34권11호
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    • pp.3345-3349
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    • 2013
  • Hsp90 shows great promise as a therapeutic target due to its potential to disable multiple signaling pathways simultaneously. In this study, we discovered that a natural product, butein moderately inhibited the growth of drug-resistant cancer cells (A2780cis and H1975), and brought about the degradation of oncogenic Hsp90 client proteins. The study demonstrated that butein would be a therapeutic lead to circumvent drug-resistance in cancer chemotherapy. The structure-based screening, synthesis, and biological evaluation of butein are described herein.

The ceRNA network of lncRNA and miRNA in lung cancer

  • Seo, Danbi;Kim, Dain;Chae, Yeonsoo;Kim, Wanyeon
    • Genomics & Informatics
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    • 제18권4호
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    • pp.36.1-36.9
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    • 2020
  • Since lung cancer is a major causative for cancer-related deaths, the investigations for discovering biomarkers to diagnose at an early stage and to apply therapeutic strategies have been continuously conducted. Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are being exponentially studied as promising biomarkers of lung cancer. Moreover, supportive evidence provides the competing endogenous RNA (ceRNA) network between lncRNAs and miRNAs participating in lung tumorigenesis. This review introduced the oncogenic or tumor-suppressive roles of lncRNAs and miRNAs in lung cancer cells and summarized the involvement of the lncRNA/miRNA ceRNA networks in carcinogenesis and therapeutic resistance of lung cancer.

Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting

  • Eun, Kiyoung;Ham, Seok Won;Kim, Hyunggee
    • BMB Reports
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    • 제50권3호
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    • pp.117-125
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    • 2017
  • Most of the cancers are still incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most promising therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, the presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, tumor recurrence, and even acquired resistance against the anti-CSC therapies developed in experimental models. One of the most forceful underlying reasons is a "cancer heterogeneity" due to "CSC plasticity". A comprehensive understanding of CSC-derived heterogeneity will provide novel insights into the establishment of efficient targeting strategies to eliminate CSCs. Here, we introduce findings on mechanisms of CSC reprogramming and CSC plasticity, which give rise to phenotypically varied CSCs. Also, we suggest concepts to improve CSC-targeted therapy in order to overcome therapeutic resistance caused by CSC plasticity and heterogeneity.

Endodontic biofilms: contemporary and future treatment options

  • Yoo, Yeon-Jee;Perinpanayagam, Hiran;Oh, Soram;Kim, A-Reum;Han, Seung-Hyun;Kum, Kee-Yeon
    • Restorative Dentistry and Endodontics
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    • 제44권1호
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    • pp.7.1-7.10
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    • 2019
  • Apical periodontitis is a biofilm-mediated infection. The biofilm protects bacteria from host defenses and increase their resistance to intracanal disinfecting protocols. Understanding the virulence of these endodontic microbiota within biofilm is essential for the development of novel therapeutic procedures for intracanal disinfection. Both the disruption of biofilms and the killing of their bacteria are necessary to effectively treat apical periodontitis. Accordingly, a review of endodontic biofilm types, antimicrobial resistance mechanisms, and current and future therapeutic procedures for endodontic biofilm is provided.

렙틴 저항성의 개선 (Improvement of Leptin Resistance)

  • 김용운
    • Journal of Yeungnam Medical Science
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    • 제30권1호
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    • pp.4-9
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    • 2013
  • Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.