Jung-Han Lee

N1-guanyl-1,7,-diamineoheptane, an inhibitor of deoxyhypusine synthase, suppresses differentiation and induces apoptosis via mitochondrial and AMPK pathways in immortalized and malignant human oral keratinocytes

BACKGROUND Although N(1)-guanyl-1,7,-diamineoheptane (GC7), an inhibitor of deoxyhypusine synthase, has been shown to inhibit cell growth, the mechanism of its action is not completely understood. In this study, we investigated the mechanisms of the effects of GC7 on cell growth, differentiation and apoptosis in relation to adenosine monophosphate-activated protein kinase (AMPK) activation, as AMPK is known to be a possible target for cancer treatment. METHODS The effects of GC7 on the growth of immortalized human oral keratinocytes (IHOK) and primary oral cancer cells (HN4), was investigated using MTT assay, Western blotting, cell cycle analysis, DNA fragmentation and expression of apoptotic pathway proteins. RESULTS N(1)-guanyl-1,7,-diamineoheptane inhibited cell proliferation in a time- and dose-dependent manner in IHOK and HN4 cells. GC7 treatment decreased the expression of differentiation markers, such as involucrin, CK13 and CK19. The major mechanism of growth inhibition by GC7 treatment was induction of apoptosis, which is supported by sub-G(1) phase arrest, annexin V-FITC staining and DNA fragmentation analysis. GC7 treatment increased the cytosolic level of cytochrome c and resulted in caspase-3 activation. GC7 treatment also resulted in a strong activation of AMPK. Furthermore, specific AMPK activator blocked the GC7-induced growth inhibition effect, as well as apoptosis. CONCLUSION These results demonstrate that GC7 blocks immortalized and malignant keratinocyte cell proliferation and differentiation by inducing apoptosis through the mitochondrial and AMPK pathways. On the basis of these observations, we propose that a strategy combining GC7 and AMPK inhibition could be developed into a novel chemotherapeutic modality in oral cancer.

An introduction to Chuna manual medicine in Korea: History, insurance coverage, education, and clinical research in Korean literature

The objectives of this study were to summarize the curriculum, history, and clinical researches of Chuna in Korea and to ultimately introduce Chuna to Western medicine. Information about the history and insurance coverage of Chuna was collected from Chuna-related institutions and papers. Data on Chuna education in all 12 Korean medicine (KM) colleges in Korea were reconstructed based on previously published papers. All available randomized controlled trials (RCTs) of Chuna in clinical research were searched using seven Korean databases and six KM journals. As a result, during the modern Chuna era, one of the three periods of Chuna, which also include the traditional Chuna era and the suppressed Chuna era, Chuna developed considerably because of a solid Korean academic system, partial insurance coverage, and the establishment of a Chuna association in Korea. All of the KM colleges offered courses on Chuna-related subjects (CRSs); however, the total number of hours dedicated to lectures on CRSs was insufficient to master Chuna completely. Overall, 17 RCTs were reviewed. Of the 14 RCTs of Chuna in musculoskeletal diseases, six reported Chuna was more effective than a control condition, and another six RCTs proposed Chuna had the same effect as a control condition. One of these 14 RCTs made the comparison impossible because of unreported statistical difference; the last RCT reported Chuna was less effective than a control condition. In addition, three RCTs of Chuna in neurological diseases reported Chuna was superior to a control condition. In conclusion, Chuna was not included in the regular curriculum in KM colleges until the modern Chuna era; Chuna became more popular as the result of it being covered by Korean insurance carriers and after the establishment of a Chuna association. Meanwhile, the currently available evidence is insufficient to characterize the effectiveness of Chuna in musculoskeletal and neurological diseases.

Development of an ultrasound-imaging procedure and acquisition of ultrasound images of acupuncture points for safety and accuracy of needle insertion

Background Acupuncture is a relatively safe, commonly used “alternative” medical treatment for various symptoms. However, adverse effects can occur, including trauma, pneumothorax, and central-nervous-system injury. Our objective was to develop a reliable and practical procedure for ultrasound imaging of acupuncture points to improve safety during needling, and to acquire ultrasound images of several (44) acupuncture points, especially those in high-risk areas, according to an in-house standard operating procedure. Methods We created the standard operating procedure for ultrasound imaging for acupuncture, and collected ultrasound images of acupuncture points in clinical trials. Results Ultrasound images for 44 acupuncture points considered as high-risk points were collected from 85 healthy people who were classified by body-mass index, and high-quality, clear representative images of all 44 points were obtained. Conclusion These baseline images could be helpful for understanding the anatomy under the skin at acupuncture points, which would allow for an enhanced safety and more accurate needling.

Economic evaluation of manual therapy for musculoskeletal diseases: a protocol for a systematic review and narrative synthesis of evidence

Introduction Manual therapy is the non-surgical conservative management of musculoskeletal disorders using the practitioners hands on the patients body for diagnosing and treating disease. The aim of this study is to systematically review trial-based economic evaluations of manual therapy relative to other interventions used for the management of musculoskeletal diseases. Methods and analysis Randomised clinical trials (RCTs) on the economic evaluation of manual therapy for musculoskeletal diseases will be included in the review. The following databases will be searched from their inception: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Econlit, Mantis, Index to Chiropractic Literature, Science Citation Index, Social Science Citation Index, Allied and Complementary Medicine Database (AMED), Cochrane Database of Systematic Reviews (CDSR), National Health Service Database of Abstracts of Reviews of Effects (NHS DARE), National Health Service Health Technology Assessment Database (NHS HTA), National Health Service Economic Evaluation Database (NHS EED), CENTRAL, five Korean medical databases (Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Service System (RISS), DBPIA, Korean Traditional Knowledge Portal (KTKP) and KoreaMed) and three Chinese databases (China National Knowledge Infrastructure (CNKI), VIP and Wanfang). The evidence for the cost-effectiveness, cost-utility and cost-benefit of manual therapy for musculoskeletal diseases will be assessed as the primary outcome. Health-related quality of life and adverse effects will be assessed as secondary outcomes. We will critically appraise the included studies using the Cochrane risk of bias tool and the Drummond checklist. Results will be summarised using Slavins qualitative best-evidence synthesis approach. Ethics and dissemination The results of the study will be disseminated via a peer-reviewed journal and/or conference presentations. Trial registration number PROSPERO CRD42015026757.