Use of traditional, complementary and alternative medicine in nine countries: A cross-sectional multinational survey.

OBJECTIVES: Traditional, complementary, and alternative medicine (TC&AM) play an exceptional role in health care around the world as many patients has sought a holistic approach. SETTING: In this study, a multinational survey was developed and administered to obtain experience, attitude, and promotion information with regard to the international use of TC&AM among nine countries: Germany, United States, Japan, China, Malaysia, Vietnam, Russia, Kazakhstan, and United Arab Emirates (UAE). The survey was administered via online to members of SurveyMonkey Audience, a proprietary panel of respondents who were recruited from a diverse population worldwide. RESULTS: A total of 1071 participants has completed the survey. The participants were in favor of the treatments and therapies as well as expressed positive attitudes and also have used herbal medicine treatment more than acupuncture therapy and also used the modalities to promote metabolism rather than treating musculoskeletal diseases. Moreover, participants mentioned that TC&AM should be applied for treating and managing infectious diseases, such as COVID-19. Additionally, participants recommended using Facebook channel to promote its treatments and therapies. CONCLUSION: Based on the results, this study provides initial insights on TC&AM that may influence the non-users globally and perhaps inspire a need for further research including more countries in different continents.

Factors influencing use of conventional and traditional Korean medicine-based health services: a nationwide cross-sectional study.

BACKGROUND: In Korea, conventional medicine (CM) and traditional Korean medicine (KM) are run as a dual healthcare system; however, the backgrounds and characteristics of the users of both medical services have not yet been compared. This study aimed to identify the differences in factors determining the use of CM and KM health services. METHODS: A secondary data analysis of a nationwide cross-sectional survey was conducted in this study. The Survey on the Experience with Healthcare Services 2017 asked participants about their most recent outpatient visit to a health service. Initially, a descriptive analysis was performed on respondents who visited the CM or KM health service in the last 12 months. Then, logistic regression analysis using Andersen's behavioral model was performed, to identify the factors affecting health service selection, by classifying demographic variables into predisposing, enabling, and need factors. Respondents who replied they did not frequently use CM/KM and those with missing data were excluded. RESULTS: Of the total 11,098 respondents, 7,116 (64.1%) reported to have used CM/KM: 2,034 (18.3%), 4,475 (40.3%), and 607 (5.5%) for hospital CM, clinic CM, and KM, respectively. In logistic regression analysis, of the 2,723 (24.5%) respondents analyzed, 822 (7.4%) went to a hospital, 1,689 (15.2%) to a clinic, and 212 (1.9%) opted for KM service. Respondents with a higher number of chronic diseases were less likely to use KM (one disease, odds ratio: 0.52, 95% confidence interval: 0.36-0.76; two diseases: 0.51, 0.31-0.85; three to five diseases: 0.26, 0.10-0.69). Respondents with a high income were likely to go to the hospital (4Q vs. 1Q: 1.92, 1.35-2.72) and less likely to go to the clinic (4Q vs. 1Q: 0.49, 0.35-0.68). CONCLUSIONS: Significant differences were observed on the enabling factor (income) for CM and need factors (number of chronic diseases) for KM. Our analysis suggests that through the healthcare policy, we should consider stratifying user backgrounds and needs for each medical service.

Spontaneously promoted osteogenic differentiation of MC3T3-E1 preosteoblasts on ultrathin layers of black phosphorus.

Recently, black phosphorus (BP) has garnered great attention as one of newly emerging two-dimensional nanomaterials. Especially, the degraded platelets of BP in the physiological environment were shown to be nontoxic phosphate anions, which are a component of bone tissue and can be used for mineralization. Here, our study presents the potential of BP as biofunctional and biocompatible nanomaterials for the application to bone tissue engineering and regeneration. An ultrathin layer of BP nanodots (BPNDs) was created on a glass substrate by using a flow-enabled self-assembly process, which yielded a highly uniform deposition of BPNDs in a unique confined geometry. The BPND-coated substrates represented unprecedented favorable topographical microenvironments and supportive matrices suitable for the growth and survival of MC3T3-E1 preosteoblasts. The prepared substrates promoted the spontaneous osteodifferentiation of preosteoblasts, which had been confirmed by determining alkaline phosphatase activity and extracellular calcium deposition as early- and late-stage markers of osteogenic differentiation, respectively. Furthermore, the BPND-coated substrates upregulated the expression of some specific genes (i.e., RUNX2, OCN, OPN, and Vinculin) and proteins, which are closely related to osteogenesis. Conclusively, our BPND-coating strategy suggests that a biologically inert surface can be readily activated as a cell-favorable nanoplatform enabled with excellent biocompatibility and osteogenic ability.

Bibliometric Analysis of Integrative Medicine Studies from 2000 to 2019.

Integrative medicine has become a vital component of patient care. It provides patient-centered care that is focused on prevention and overall well-being. As there has been a growing number of patients favoring a blend of conventional, complementary and alternative approaches, integrative medicine has exceeded beyond the evaluation of complementary therapies. However, it is noteworthy that there has been a dilemma of providing substantial evidence supporting the efficacy of some complementary and alternative therapies. This study's goals were to analyze publication trends, most productive journals, most productive funding agencies, most productive authors, most relevant keywords, and countries in the field of integrative medicine research. Additionally, science mapping included country collaboration analysis and thematic evolution analysis. The findings from this study showed a constant rise in annual growth of publications from 2000 to 2019; the United States was dominant in various analysis categories. In conclusion, a comprehensive review of the evolution of research of integrative medicine will help healthcare providers understand an overview of the present status while encouraging more evidence-based research for the betterment of integrative patient care.

Adverse events from pharmacopuncture treatment in Korea: A protocol for systematic review and meta analysis.

BACKGROUND: Pharmacopuncture is a combination of acupuncture and herbal medicine, which involves the injection of herbal extracts into acupuncture points (acupoints). Pharmacopuncture has become one of the major therapeutic tools used in Korea; however, safety is one of the major concerns associated with it. We aim to systematically review clinical studies on the adverse events of pharmacopuncture in Korea. METHODS: To collect data on the incidence and characteristics of adverse events (AEs) and to evaluate pharmacopuncture safety, 2 or more researchers will conduct a comprehensive search of pertinent English and Korean databases using the keywords "pharmacopuncture" and "adverse events." Regardless of the participants' conditions or treatment types, we will include clinical studies on the AEs of pharmacopuncture. Studies that were not conducted in Korea, and acupoint injections containing Western medications, vitamins, or autologous serum will be excluded from this study. The severity of AEs will be classified using the common terminology criteria for adverse events, and the causality between pharmacopuncture and AEs will be assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality scale. The quality of identifying and reporting the AEs will be assessed using the McHarm scale. The risk of selection bias will be assessed using the Cochrane risk of bias and the risk of bias for non-randomized studies tools. Studies will be assessed for heterogeneity utilizing Higgins's I2 statistics, and the risk of publication bias will be assessed and expressed in the form of a contour-enhanced funnel plot. RESULTS AND CONCLUSION: Comprehensive investigation of all types of clinical studies in Korea will provide clearer evidence of the safety of pharmacopuncture. The results of this study will be useful for traditional medical doctors and patients who use such treatments and interventions.Systematic Review Registration: Open Science Foundation (osf.io/umhyz).

Utilization of traditional medicine in primary health care in low- and middle-income countries: a systematic review.

This paper reports the findings from the first systematic review of the utilization of traditional medicine (TM) in primary health care (PHC) in low- and middle-income countries (LMICs). PHC is an important component of health care and essential for achieving universal health coverage (UHC). For countries where there is a gap in PHC, TM plays a vital role. It is widely used and has the potential to increase the coverage of PHC and UHC. Hence in situations where TM is recognized in a considerable magnitude, there are scarce evidence and minimal regulation on it and TM practitioners (TMPs). This study aims to identify the current situation in the utilization of TM in PHC or UHC in LMICs. A systematic review and thematic synthesis of qualitative and quantitative studies have been conducted. A total of 56 articles met the criteria and were included in the review. In all, 14 analytic themes have been developed including the current use of TM in PHC, higher accessibility of TM, medical pluralism, national health system, national health policy and national health insurance to include TM, including TMPs in the referral system, utilizing TMPs as community health workers, the needs of scientific research on TM and the need for training both TMPs and conventional medical staffs for better collaboration. The study concluded that it is necessary to further focus on TM in the macro level on strengthening the referral system by including TM to establish a comprehensive service delivery network under UHC and in the micro level to focus on training the TMPs and conventional medicine health workers on both areas to attain more in-depth understanding of each other, which can lead to better collaboration and quality patient care.

Synergistic anticancer effect of combined use of Trichosanthes kirilowii with cisplatin and pemetrexed enhances apoptosis of H1299 non-small-cell lung cancer cells via modulation of ErbB3.

BACKGROUND: Lung cancer is one of the most common malignancies worldwide. To treat lung cancer, various anticancer drugs were developed and tested, but they failed because of drug resistance. In the present study, we tested herbal medicines, such as TK and CuD, as anticancer drugs to decrease side effects and resistance. METHODS: Cell viability was measured by an MTT assay. Analysis of cell cycle arrest was performed by flow cytometry. Induction of apoptosis by cucurbitacin D was measured by an annexin V-FITC/PI assay. We performed RTK kit analysis. Levels of p-ErbB3, p-STAT3, p-NF-κB, and caspases were measured by western blot analysis. Nuclear staining of ErbB3 was measured by immunocytochemistry. Transcriptional activity of STAT3 and NF-κB was detected by STAT3 and NF-κB luciferase reporter gene assays. RESULTS: We found a synergistic effect of TK with CDDP and PXD in primary culture of human NSCLC tumor cells. The combination of CDDP/PXD and TK or CuD inhibited the proliferation of H1299 cells. The combination of CDDP/PXD and TK or CuD induced sub-G1 and G2/M cell cycle arrest in H1299 cells. The combination of CDDP/PXD and TK or CuD induced apoptosis, regulated apoptotic molecules, caused morphological changes and inhibited colony formation in H1299 cells. We found that TK suppresses p-ErbB3 expression and signaling. The combination of CDDP/PXD and TK or CuD inhibited p-AKT, p-Erk, and p-JNK signaling and suppressed Stat3 and NF-κB transcriptional activity in H1299 cells. More importantly, the combination of CDDP/PXD and TK or CuD inhibited p-ErbB3 and downstream molecules in H1299 cells. The combination of CDDP/PXD and TK or CuD inhibited ErbB2/ErbB3 dimerization. Our results clearly demonstrate that the synergistic effect of CDDP/PXD and TK or CuD inhibits cell growth and induces apoptosis by inhibiting ErbB3 signaling. CONCLUSION: The combination of CDDP/PXD and TK or CuD decreases cell proliferation and induces apoptosis by inhibiting ErbB3 signaling in H1299 lung cancer cells. TK or CuD could be useful as a compound to treat lung cancer. Additionally, targeting ErbB3 may also be useful for treating lung cancer.

Clinical Effectiveness of Traditional and Complementary Medicine Interventions in Combination with Nicotine Replacement Therapy on Smoking Cessation: A Randomized Controlled Pilot Trial.

Background: Smoking is associated with many preventable diseases and deaths. Globally, more than 6 million deaths per year are related to smoking. This study aimed to evaluate the pragmatic effectiveness of traditional and complementary medicine (T&CM) interventions for the smoking cessation treatment and to calculate the incremental cost-effectiveness ratio (ICER) of these interventions. Methods: The study design was a pragmatic, open-label randomized trial. The hypothesis of this trial was that the smoking cessation success rate increases with the addition of T&CM methods. The intervention group was provided T&CM interventions in addition to nicotine replacement therapy (NRT) and counseling, whereas the control group was treated with only NRT and counseling. Individuals received treatment for 4 weeks, then follow-up care for 20 weeks. Results: Forty-one participants were enrolled and assigned to either an intervention group or a control group at a ratio of 1:1. The odds ratio values at 4 weeks were 1.96 (0.51-8.51) in intention-to-treat analysis and 3.27 (0.75-17.75) in per-protocol analysis. The amount of smoking (cigarettes) decreased in both groups: from 17.2 ± 10.31 (baseline) to 1.7 ± 3.02 (4 weeks) in the intervention group and from 12.9 ± 5.47 (baseline) to 3.3 ± 5.96 (4 weeks) in the control group. The total medical costs per patient were $212.20 USD in the intervention group and $170.80 in the control group. The adjusted ICER of T&CM interventions was $13,355. Conclusions: This pilot study evaluated the clinical feasibility of T&CM used in conjunction with NRT and counseling for the smoking cessation treatment. However, there was no statistically significant effectiveness of T&CM interventions to raise cessation success rate. This study demonstrates the necessity for further studies based on large-scale randomized controlled trials.

Oral administration of Cervus nippon mantchuricus extract suppresses 2,4-dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice and inflammatory effects in mast cells.

Cervus nippon mantchuricus extract, known as nok­gol (NGE) in Korean, is useful for the treatment of various inflammatory diseases, including bone resorption and neutropenia. However, NGE has not been widely investigated, and its efficacy and safety remain to be fully elucidated. In the present study, histological analysis, blood analysis, reverse transcription­semi-quantitative polymerase chain reaction analysis and enzyme­linked immunosorbent assays were performed to verify the inhibitory effect of NGE on atopic dermatitis (AD) in BALB/c mice and on inflammatory effects in HMC­1 human mast cells. NGE suppressed the development of AD in mice, and decreased the infiltration of inflammatory cells, mast cells and CD4+ T cells into AD skin lesions. NGE also decreased leukocyte levels induced by 2,4­dinitrochlorobenzene (DNCB). NGE alleviated AD­like inflammatory symptoms in mice by suppressing the production of CD4+ T cells. NGE downregulated the mRNA expression of inflammatory cytokines induced by DNCB. It also decreased the serum immunoglobulin E concentration and inflammatory cytokine levels in DNCB­treated BALB/c mice. The in vitro experiments demonstrated that NGE reduced the phorbol 12­myristate 13­acetate + ionomycin­induced expression of pro­inflammatory cytokines interleukin (IL)­4, IL­13, tumor necrosis factor­α, and IL­6 in HMC­1 cells. Taken together, the results of the present study indicated that NGE suppressed the progression of DNCB­induced AD in BALB/c mice and reduced inflammatory effects in HMC­1 cells. This suggests that NGE may be a useful drug for the treatment of AD.

Single-arm, open-label, dose-escalation phase I study to evaluate the safety of a herbal medicine SH003 in patients with solid cancer: a study protocol.

INTRODUCTION: Cancer is a major health problem worldwide and the leading cause of death in many countries. The number of patients with cancer and socioeconomic costs of cancer continues to increase. SH003 is a novel herbal medicine consisting of Astragalus membranaceus, Angelica gigas and Trichosanthes Kirilowii Maximowicz. Preclinical studies have shown that SH003 has therapeutic anticancer effects. The aim of this study is to determine the maximum tolerated dose of SH003 in patients with solid cancers. METHODS AND ANALYSIS: This study is an open-label, dose-escalation trial evaluating the safety and tolerability of SH003. The traditional 3+3 dose-escalation design will be implemented. Patients with solid cancers will be recruited. According to dose level, the patients will receive one to four tablets of SH003, three times a day for 3 weeks. Toxicity will be evaluated using common terminology criteria for adverse events (CTCAE). Dose-limiting toxicities are defined as grade 3 or higher adverse events based on CTCAE. The maximum tolerated dose will be determined by the highest dose at which no more than one of six patients experiences dose-limiting toxicity. ETHICS AND DISSEMINATION: This study has been approved by the institutional review board of the Ajou University Hospital (reference AJIRB-MED-CT1-16-311). The results of this study will be disseminated through a scientific journal and a conference. TRIAL REGISTRATION NUMBER: NCT03081819; Pre-results.

Corrigendum to "Efficacy and Safety of Sipjeondaebo-Tang for Anorexia in Patients with Cancer: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial".

[This corrects the article DOI: 10.1155/2017/8780325.].

Maekmoondong-tang in treatment of postoperative cough in patients with lung cancer: Study protocol for a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Cough is a common symptom that occurs in 25% of patients after lung cancer surgery. It might last a long time and degrade the quality of life of patients. Maekmoondong-tang (Bakumondo-to in Japanese or Mai-Men-Dong-Tang in Chinese) is a herbal medicine which has been widely used for respiratory diseases with cough in Korea, China, and Japan. AIMS: The aim of the present study is to evaluate the efficacy and safety of Maekmoondong-tang for postoperative cough in patient with lung cancer. METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled, multicenter trial of Maekmoondong-tang. A total of 96 participants will be enrolled and allocated to 2 parallel groups: the Maekmoondong-tang group and the placebo group from 5 university hospitals. The participants will be administered either Maekmoondong-tang or a placebo 3 times a day for 4 weeks. The primary outcome measurement is the change in the Leicester Cough Questionnaire (LCQ) score. The secondary outcome measurements are the changes in the cough visual analog scale and Yin Deficiency Scale. The participants will visit 4 times in total for 4 weeks of trial period. DISCUSSION: The present study will be the first multicener study to evaluate the efficacy and safety of Maekmoondong-tang for postoperative cough in patient with lung cancer surgery. The results of this study will provide a new treatment for cough using herbal medicine and will be a reference for planning clinical trial of herbal medicine in patient with cough.

The prevention of 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo.

BACKGROUND: Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand its underlying cellular mechanisms. METHODS: AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. Treatment with Jawoongo was assessed to study the effect of Jawoongo on AD in mice. Histological Analysis, blood analysis, RT-PCR, western blot analysis, ELISA assay and cell viability assay were performed to verify the inhibitory effect of Jawoongo on AD in mice. RESULTS: We found that application of Jawoongo in an ointment form on AD-like skin lesions on DNCB-exposed BALB/c mice reduced skin thickness and ameliorated skin infiltration with inflammatory cells, mast cells and CD4+ cells. The ointment also reduced the mRNA levels of IL-2, IL-4, IL-13 and TNF-α in the sensitized skin. Leukocyte counts and the levels of IgE, IL-6, IL-10 and IL-12 were decreased in the blood of the DNCB-treated mice. Furthermore, studies on cultured cells demonstrated that Jawoongo exhibits anti-inflammatory activities, including the suppression of proinflammatory cytokine expression, nitric oxide (NO) production, and inflammation-associated molecule levels in numerous types of agonist-stimulated innate immune cell, including human mast cells (HMC-1), murine macrophage RAW264.7 cells, and splenocytes isolated from mice. CONCLUSION: These findings indicate that Jawoongo alleviates DNCB-induced AD-like symptoms via the modulation of several inflammatory responses, indicating that Jawoongo might be a useful drug for the treatment of AD.

Sipjeondaebo-tang in patients with breast cancer with fatigue: a protocol for a pilot, randomised, double-blind, placebo-controlled, cross-over trial.

INTRODUCTION: Cancer-related fatigue is a frequent symptom in patients with cancer and one of the most distressing symptoms in patients with breast cancer. Sipjeondaebo-tang (Juzen-taiho-to in Japanese or Shi-Quan-Da-Bu-Tang in Chinese) is a widely used herbal medicine for the treatment of fatigue in Korea, China and Japan. The purpose of the present study is to evaluate the feasibility of Sipjeondaebo-tang for cancer-related fatigue. METHODS AND ANALYSIS: The present study is a randomised, double-blind, placebo-controlled, cross-over study. Forty-eight patients with breast cancer who are indicated for doxorubicin and cyclophosphamide will be recruited. The participants will receive 3 g of Sipjeondaebo-tang or a placebo three times a day for 56 days. The primary outcome measurement is the change in the Brief Fatigue Inventory scores. The secondary outcome measurements include the changes in the Visual Analogue Scale (VAS) of fatigue, and quality of life measured by the European Organization for Research and Treatment of Cancer-QLQ-C30 and QLQ-BR23. VAS of fatigue will be measured on every visit, and other outcomes will be measured on visits 2, 4, 6 and 7. The total study period is 14 weeks. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of the Catholic Kwandong University International St Mary's Hospital (reference IS16MNSI0011). The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: NCT02858856; Pre-results.

DSGOST regulates resistance via activation of autophagy in gastric cancer.

Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST in Korean, Danggui-Sini-Jia-Wuzhuyu-Shengian-Tang in Chinese, and Tokishigyakukagoshuyushokyoto (TJ-38) in Japanese), a well-known traditional Korean/Chinese/Japanese medicine, has long been used to treat vascular diseases such as Raynaud's phenomenon (RP). However, anticancer effect of DSGOST remains elusive. In this study, we checked if DSGOST has an anticancer effect against gastric cancer cells, and investigated the mechanisms underlying DSGOST resistance. Moreover, DSGOST regulates chemoresistance in cisplatin-treated gastric cancer cells. Interestingly, DSGOST treatment induced the accumulation of GFP-LC3 puncta and increased the level of autophagy markers, such as LC3-II, ATG5, and Beclin-1, indicating activated autophagy. Furthermore, DSGOST could activate epithelial-to-mesenchymal transition (EMT) and exosomes via induction of autophagy. DSGOST in combination with TGFß also induced autophagy and EMT. However, autophagy inhibition induces DSGOST-mediated cell death in gastric cancer cells. In addition, autophagy inhibition blocks the activation of DSGOST-mediated EMT markers including N-cadherin, Snail, Slug, vimentin, ß-catenin, p-Smad2, and p-Smad3. Taken together, these findings indicated that prosurvival autophagy was one of the mechanisms involved in the resistance of gastric cancer to DSGOST. Targeting the inhibition of autophagy could be an effective therapeutic approach to overcome resistance to DSGOST in gastric cancer.

SH003 suppresses breast cancer growth by accumulating p62 in autolysosomes.

Drug markets revisits herbal medicines, as historical usages address their therapeutic efficacies with less adverse effects. Moreover, herbal medicines save both cost and time in development. SH003, a modified version of traditional herbal medicine extracted from Astragalus membranaceus (Am), Angelica gigas (Ag), and Trichosanthes Kirilowii Maximowicz (Tk) with 1:1:1 ratio (w/w) has been revealed to inhibit tumor growth and metastasis on highly metastatic breast cancer cells, both in vivo and in vitro with no toxicity. Meanwhile, autophagy is imperative for maintenance cellular homeostasis, thereby playing critical roles in cancer progression. Inhibition of autophagy by pharmacological agents induces apoptotic cell death in cancer cells, resulting in cancer treatment. In this study, we demonstrate that SH003-induced autophagy via inhibiting STAT3 and mTOR results in an induction of lysosomal p62/SQSTM1 accumulation-mediated reactive oxygen species (ROS) generation and attenuates tumor growth. SH003 induced autophagosome and autolysosome formation by inhibiting activation of STAT3- and mTOR-mediated signaling pathways. However, SH003 blocked autophagy-mediated p62/SQSTM1 degradation through reducing of lysosomal proteases, Cathepsins, resulting in accumulation of p62/SQSTM1 in the lysosome. The accumulation of p62/SQSTM1 caused the increase of ROS, which resulted in the induction of apoptotic cell death. Therefore, we conclude that SH003 suppresses breast cancer growth by inducing autophagy. In addition, SH003-induced p62/SQSTM1 could function as an important mediator for ROS generation-dependent cell death suggesting that SH003 may be useful for treating breast cancer.

SH003 reverses drug resistance by blocking signal transducer and activator of transcription 3 (STAT3) signaling in breast cancer cells.

Overcoming drug resistance is an important task for investigators and clinician to achieve successful chemotherapy in cancer patients. Drug resistance is caused by various factors, including the overexpression of P-glycoprotein (P-gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. SH003 is extracted from the mixture of three different herbs, and its anticancer effect has been revealed in different cancer cell types. In the present study, we investigated whether SH003 is able to reverse drug resistance using paclitaxel-resistant breast cancer cells (MCF-7/PAC). In our experiments, SH003 significantly decreased cell growth and colony formation in MCF-7/PAC cells and parental MCF-7 cells. This growth inhibition was related to the accumulation of cells in the sub-G0/G1 apoptotic population and an increase in the number of apoptotic cells. SH003 reduced the mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated proteins (MRPs) in MCF-7/PAC cells. SH003 also down-regulated the expression of P-gp. SH003 reversed drug efflux from MCF-7/PAC cells, resulting in rhodamine123 (Rho123) accumulation. Inhibition of drug resistance by SH003 is related to the suppression of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. SH003 decreased STAT3 activation (p-STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP-2, which are STAT3 target genes. An STAT3 inhibitor, JAK inhibitor I and an HIF-1α inhibitor decreased cell growth in MCF-7 and MCF-7/PAC cells. Taken together, these results demonstrate that SH003 can overcome drug resistance, and SH003 might be helpful for chemotherapy in cancer patients.

The immune-enhancing activity of Cervus nippon mantchuricus extract (NGE) in RAW264.7 macrophage cells and immunosuppressed mice.

Chemotherapeutics are often used to inhibit the proliferation of cancer cells. However, they can also harm healthy cells and cause side effects such as immunosuppression. Especially traditional oriental medicines long used in Asia, may be beneficial candidates for the alleviation of immune diseases. Cervus nippon mantchuricus extract (NGE) is currently sold in the market as coffee and health drinks. However, NGE was not widely investigated and efficacy remain unclear and essentially nothing is known about their potential immune-regulatory properties. As a result, NGE induced the differentiation of RAW264.7 macrophage cells. NGE-stimulated RAW264.7 macrophage cells elevated cytokines levels and NO production. NGE-stimulated RAW264.7 macrophage cells activated MAPKs and NF-κB signaling pathways. NGE encouraged the immuno-enhancing effects in immunosuppressed short-term treated with NGE mice model. NGE or Red ginseng encouraged the immuno-enhancing effects in immunosuppressed long-term treated with NGE mice model. Our data clearly show that NGE contains immune-enhancing activity and can be used to treat immunodeficiency.

Euiiyin-tang in the treatment of obesity: study protocol for a randomised controlled trial.

BACKGROUND: Obesity is a public health concern in many countries due to its increasing prevalence. Euiiyin-tang is an herbal medicine formula often used as a clinical treatment for obesity. It acts to eliminate humidity and purify the blood, the causes of obesity identified by the theoretical framework of Korean medicine. The purpose of this study is to evaluate the efficacy and safety of Euiiyin-tang in treating obesity. METHODS/DESIGN: This study is a randomised, double-blinded and placebo-controlled, multicentre trial. It has two parallel arms: the Euiiyin-tang group and the placebo group. A total of 160 obese adult women will be enrolled in the trial. The participants will be randomly divided at a 1:1 ratio at visit 2 (baseline). The participants will be administered Euiiyin-tang or placebo for 12 weeks. The primary endpoint is the change in weight occurring between baseline and post-treatment. The secondary outcomes include average weight reduction, changes in body fat, waist and hip circumferences, body mass index, and lipid profile, and the results of questionnaires such as the Korean version of Obesity-related Quality of Life, the Korean version of Eating Attitudes Test, the Social Readjustment Rating Scale, and the Stress Reaction Inventory. DISCUSSION: The present study will provide research methodologies for evaluating the efficacy and safety of Euiiyin-tang in patients with obesity. In addition, it will provide evidence of correlation between obesity and Sasang constitutional medicine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01724099 . Registered on 2 November 2012.

Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy.

INTRODUCTION: Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. METHODS AND ANALYSIS: The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11-1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants, and the investigators will explain the study to the participants in detail. As an ethical clinical trial, the control group will also be given conventional cessation treatments, including NRT and counselling. Participants will be screened and provided with a registration number to protect their personal information. Informed consent will be obtained from the participants prior to enrolling them in the trial. Participants will be allowed to withdraw at anytime without penalty. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02768025); pre-results.