Association between WHO First-Step Analgesic Use and Risk of Breast Cancer in Women of Working Age.

We assessed the association between breast cancer and analgesic use in women of a specific working-age group. The Korean National Health Insurance Service-National Sample Cohort database (KNHIS-NSC) data were analyzed. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for patients' cancer risk based on whether the women participated in economic activity (PEA or not PEA (NPEA) groups) and analgesic use. Additionally, breast cancer incidence variations by age group, and PEA or NPEAs, health behavior, Charlson Comorbidity Index, and analgesic use were evaluated. The PEA group had a higher cancer risk than the NPEA group (HR = 1.542, 95% CI: 1.345-1.768, p < 0.001). Breast cancer risk was high in the PEA, high income, and no history of exercise groups, but significantly reduced in the regular-use-of-analgesics group. Notably, the working age group of 40~49 years, within the PEA group, had the highest HR of breast cancer development (HR = 1.700, 95% CI = 1.361-2.124, p < 0.001); whereas regular analgesic use in those aged 25~39 years decreased breast cancer risk (HR = 0.611, 95% CI = 0.427-0.875, p < 0.05). In conclusion, our results suggest that individuals at a high-risk of comorbidity may benefit from regular use of analgesics, which may prove to be a useful strategy for breast cancer prevention in the Young-aged group.

Association between first-step analgesic use and cancer in patients with diabetes.

OBJECTIVES: This study aimed to determine the effectiveness of analgesics in inhibiting cancer development in patients with diabetes based on a sample cohort supplied by the Korean National Health Insurance Service. MATERIALS AND METHODS: Regular users of analgesics included those using prescription analgesics ≥ 15 days per month at least 6 times over 2 years after the diagnosis of diabetes mellitus (baseline). The effectiveness of analgesics in patients with diabetes was evaluated using metformin adherence and three models: model 1 was adjusted for age and sex; model 2 was further adjusted for body mass index (BMI), exercise, cholesterol, hypertension, and Charlson comorbidity index (CCI); and model 3 was further adjusted for analgesics. RESULTS: Based on stringent extraction criteria, the sample had a cancer incidence of 4.6%. The hazard ratios of models 1 and 2 were 0.830 and 0.865, respectively. The adjusted hazard ratio for all variables, including acetaminophen and nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen, was 0.871 (model 3). CONCLUSION: Regular use of analgesics by patients with diabetes decreased their risk of subsequent cancer development in this large national cohort. Compared with participants who did not develop cancer, those with cancer were older and more likely to be male, did not exercise, have more comorbidities (as assessed by CCI), and did not use analgesics regularly.

Temporal patterns of chronic disease incidence after breast cancer: a nationwide population-based cohort study.

We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyroidism, type 2 diabetes, hypertension and hyperlipidemia. The development of breast cancer was associated with a significantly increased risk of all outcomes analyzed except for ESRD and hypertension. The fully-adjusted risks of leukemia (HR 3.09; 95% CI 2.11-4.51), cardiomyopathy (HR 2.65; 95% CI 1.90-3.68), endometrial cancer (HR 3.53; 95% CI 2.76-4.53), hypothyroidism (HR 1.29; 95% CI 1.19-1.40), pulmonary fibrosis (HR 1.84; 95% CI 1.12-3.02), and hyperlipidemia (HR 1.24; 95% CI 1.20-1.28) remained significantly elevated after more than 5 years since diagnosis. Optimal care for breast cancer survivors requires close collaboration between oncologists and allied health care professionals to identify and manage the long-term morbidity and mortality associated with these chronic conditions.

Impact of objective financial burden and subjective financial distress on spiritual well-being and quality of life among working-age cancer survivors.

PURPOSE: To assess objective financial burden (OFB) and subjective financial distress (SFD) amikong working-age cancer survivors and evaluate their association with spiritual well-being and health-related quality of life (HRQoL). METHODS: This is a multicenter cross-sectional survey of cancer survivors working at diagnosis between 2017 and 2018. OFB was defined as patients with high medical payments for individuals/households, debt due to cancer care costs, or bankruptcy. SFD was measured using a questionnaire. Fear of cancer recurrence (FCR), spiritual well-being, and HRQoL were also assessed. RESULTS: Among 727 participants, 31% reported that they experienced financial toxicity, and 12% and 26% had OFB and SFD, respectively. The No-OFB-SFD, OFB-No-SFD, and OFB-SFD groups were 4.90, 1.82, and 7.81 times more likely to experience uncertainty than the No-OFB-No-SFD group. Furthermore, the No-OFB-SFD, OFB-No-SFD, and OFB-SFD groups were 1.92, 1.35, and 2.53 times more likely to report lost purpose of life, respectively. Overall QoL and health status in the No-OFB-No-SFD, No-OFB-SFD, OFB-No-SFD, and OFB-SFD groups were 63.1, 42.9, 57.0, and 41.2, respectively. Survivors who had SFD regardless of OFB had lower HRQoL and functioning, and higher symptoms than those of the survivors without SFD. CONCLUSION: Financial toxicity was associated with FCR, uncertainty, loss of purpose, and loss of hope among working-age cancer survivors, even in a universal care setting. It is associated with FCR, uncertainty, loss of purpose, and loss of hope. It is necessary to inform survivors of the financial implications of cancer care to allow them to prepare financially as needed.

Validation of Cancer Diagnosis Based on the National Health Insurance Service Database versus the National Cancer Registry Database in Korea.

PURPOSE: This study aimed to assess the feasibility of operational definitions of cancer patients in conducting cancer-related studies using the claims data from the National Health Insurance Service (NHIS). MATERIALS AND METHODS: Cancer incidence data were obtained from the Korean Central Cancer Registry, the NHIS primary diagnosis, and from the rare and intractable disease (RID) registration program. RESULTS: The operational definition with higher sensitivity for cancer patient verification was different by cancer type. Using primary diagnosis, the lowest sensitivity was found in colorectal cancer (91.5%; 95% confidence interval [CI], 91.7 to 92.0) and the highest sensitivity was found in breast cancer (97.9%; 95% CI, 97.8 to 98.0). With RID, sensitivity was the lowest in liver cancer (91.9%; 95% CI, 91.7 to 92.0) and highest in breast cancer (98.1%; 95% CI, 98.0 to 98.2). In terms of the difference in the date of diagnosis in the cancer registration data, > 80% of the patients showed a < 31-day difference from the RID definition. CONCLUSION: Based on the NHIS data, the operational definition of cancer incidence is more accurate when using the RID registration program claims compared to using the primary diagnosis despite the relatively lower concordance by cancer type requires additional definitions such as treatment.

Effects of early medication treatment and metformin use for cancer prevention in diabetes patients: a nationwide sample cohort study in Korea using extended landmark time analysis.

OBJECTIVES: This study investigated the effectiveness of early medication treatment and metformin use for cancer prevention in type 2 diabetes patients. METHODS: Population-based cohort data were used from the Korean National Health Insurance Service-National Sample Cohort database (KNHIS-NSC) for 2002-2013. Patient-specific medication prescription status was defined by the landmark time (LMT; a fixed time after cohort entry), considering both pre- and post-LMT prescriptions to control methodological biases in observational research. The LMT was set to 2 years. Logistic regression analysis with multivariable adjustment was conducted to analyze cancer incidence by patient-specific medication prescription status. RESULTS: Only 33.4% of the subjects were prescribed medication early (before the LMT) with compliance. Cancer incidence in individuals with early prescription and compliance was 25% lower (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.67 to 0.84) than in those without. As early-prescribed medications, metformin monotherapy and metformin combination therapy were associated with 34% (OR, 0.66; 95% CI, 0.51 to 0.83) and 25% (OR, 0.75; 95% CI, 0.64 to 0.88) lower cancer risk than non-use, respectively. Patients who were prescribed late (post-LMT) but did not comply with the prescription had a 24% (OR, 1.24; 95% CI, 0.97 to 1.58) higher cancer incidence than non-users. Among patients who started monotherapy early without changes throughout the entire follow-up period, those who started on metformin had a 37% (OR, 0.63; 95% CI, 0.41 to 0.99) lower risk of cancer than non-metformin users. CONCLUSIONS: Doctors must prescribe antidiabetic medication early, and patient compliance is required, regardless of the prescription time, to prevent cancer. Metformin monotherapy or combination therapy is recommended as an early prescription.

Prescribing patterns in breast cancer survivors: A Korean National Health Insurance Service cohort study.

PURPOSE: Breast cancer survivors often manifest comorbidities that require medication management. This study aimed to investigate the prescription patterns of drugs prescribed frequently among breast cancer survivors and to provide data to monitor adverse effects using other covariates in these patients. MATERIALS AND METHODS: We analyzed a Korean national sample cohort database. The diagnosis of breast cancer, survival, survival duration, and frequency of drug prescription were first defined and extracted. We then analyzed the frequency of drug prescription in breast cancer by survival duration. Factors associated with drug prescribing patterns were analyzed using logistic regression analysis. RESULTS: Among 2,410 breast cancer survivors, anti-hormonal agents, gastrointestinal drugs, calcium, and anxiolytics were most frequently prescribed. Gastrointestinal disturbance and depression are most commonly observed among breast cancer survivors. Survivors who were 3 to < 5 years post treatment were frequently prescribed calcium. In addition to gastrointestinal drugs, anxiolytics were frequently prescribed among survivors manifesting comorbidities. In addition to anti-hormone agents, which were frequently prescribed to breast cancer patients, gastrointestinal drugs were the second most frequently prescribed, and anxiolytics were often co-prescribed. Calcium was also frequently co-prescribed in patients requiring anti-depressants. CONCLUSION: In the Korean National Cohort, gastrointestinal drugs, calcium, and anxiolytics were frequently prescribed to older patients, suggesting that older patients diagnosed with cancer experience a wide array of toxicities requiring supportive care.

Influence of Metabolic Syndrome on Risk of Breast Cancer: A Study Analyzing Nationwide Data from Korean National Health Insurance Service.

BACKGROUND: To investigate the influence of metabolic syndrome and its components on the risk of breast cancer. METHODS: Retrospective nationwide cohort study analyzing data of 13,377,349 women older than 19 years from Korean National Health Insurance Service was performed. Cox proportional hazards model was used to calculate HR and 95% confidence interval (CI) of breast cancer risk. RESULTS: The presence of metabolic syndrome decreased the risk of all breast cancer types in all subjects (HR, 0.954; 95% CI, 0.939-0.970). In women with age ≤50 years, metabolic syndrome decreased the risk of all breast cancer types, with similar findings for all subject groups (HR, 0.915; 95% CI, 0.892-0.939). In women with age >50 years, metabolic syndrome increased the risk of all breast cancer types (HR, 1.146; 95% CI, 1.123-1.170), especially in age groups of more than 55 years. In women with age >50 years, HRs increased as the number of metabolic syndrome components increased, while HRs decreased as the number of metabolic syndrome components increased in women with age ≤50 years. CONCLUSIONS: The presence of metabolic syndrome increased the risk of breast cancers in postmenopausal women, but decreased the risk in premenopausal women. Every metabolic syndrome component played similar roles on the risk of breast cancer as metabolic syndrome, and their effects became stronger when the number of components increased. IMPACT: Metabolic syndrome is associated with the risk of breast cancer having different effect according to age groups.

Care Pathway for Cancer Survivorship in Korea: Trend of Breast Cancer Pathway from 2003 to 2010.

OBJECTIVES: The survival rate of cancer patients has exceeded 60%. Although cancer survivors may die of other diseases except cancer, the health management system including chronic disease prevention-management for cancer survivors, has not been established in the diverse aspects. Therefore, services according to care pathway of cancer patients need to be provided through a support system based on a platform concept that can be used to meet patient needs in various ways. METHODS: A sample cohort database (2002-2010) of approximately 1 million persons-2% of the whole nation (50 million)-was used to estimate cancer survivors through a principal care pathway for cancer management. The sample cohort database was built to estimate the number of breast cancer survivors in the five stage: 'Diagnosis and treatment,' 'Supportive care,' 'Monitoring,' 'Progress illness,' and 'Hospice care'. In this way, the scale of breast cancer survivors was estimated. RESULTS: There were 330 (9.8%) cases of the incidence of cancer in 2010 in the 'Diagnosis and treatment.' Among the cases of the incidence of cancer in the previous year, the number of one-year survivors was 328 (9.7%); these were included in the category 'Supportive care.' In the 'Monitoring' category, 2,593 (76.9%) who maintained health lives were included. A total of 84 (2.5%) survivors were checked to identify an ongoing disease; these were included in the category 'Progress illness.' In the category 'Hospice care,' 36 (1.1%) end-stage cancer patients requiring hospice care were included. CONCLUSIONS: We established a care pathway by survival stage in order to fulfill prevention and health management services post-treatment management steps.

Acceptability of Service Targets for ICT-Based Healthcare.

OBJECTIVES: In order to adopt and activate telemedicine it is necessary to survey how medical staff, who are providers of medical service, and consumers, who are the service targets, perceive information and communication technology (ICT)-based healthcare service. METHODS: This study surveyed the awareness and acceptability of ICT-based healthcare by involving service targets, specifically workers and students living in the Seoul and Gyeonggi regions who are consumers of healthcare service. To determine the correlation among awareness of ICT-based healthcare, the need for self-management, and acceptability, this study conducted a correlation analysis and a simple regression analysis. RESULTS: According to the responses to the questions on the need for ICT-based healthcare service by item, blood pressure (n = 279, 94.3%) and glucose (n = 277, 93.6%) were revealed to be the physiological signal monitoring area. Among the six measurement factors affecting ICT-based healthcare service acceptability, age, health concerns, and effect expectation had the most significant effects. As effect expectation increased, acceptability became 4.38 times higher (p < 0.05). CONCLUSIONS: This study identified a positive awareness of service targets on ICT-based healthcare service. The fact that acceptability is higher among people who have family disease history or greater health concerns may lead to service targets' more active participation. This study also confirmed that a policy to motivate active participation of those in their 40s (who had high prevalence rates) was needed.

Development of a Tailored Analysis System for Korean Working Conditions Survey.

BACKGROUND: Korean Working Conditions Surveys (KWCS), referencing European Working Conditions Surveys, have been conducted three times in order to survey working condition and develop work-related policies. However, we found three limitations for managing the collected KWCS data: (1) there was no computerized system for managing data; (2) statistical KWCS data were provided by limited one-way communication; and (3) the concept of a one-time provision of information was pursued. We suggest a web-based public service system that enables ordinary people to make greater use of the KWCS data, which can be managed constantly in the future. METHODS: After considering data characteristics, we designed a database, which was able to have the result of all pairwise combinations with two extracted data to construct an analysis system. Using the data of the social network for each user, the tailored analysis system was developed. This system was developed with three methods: clustering and classification for building a social network, and an infographic method for improving readability through a friendly user interface. RESULTS: We developed a database including one input entity consisting of the sociodemographic characteristics and one output entity consisting of working condition characteristics, such as working pattern and work satisfaction. A web-based public service system to provide tailored contents was completed. CONCLUSION: This study aimed to present a customized analysis system to use the KWCS data efficiently, provide a large amount of data in a form that can give users a better understanding, and lay the ground for helping researchers and policy makers understand the characteristics.

Standard based deposit guideline for distribution of human biological materials in cancer patients.

BACKGROUND: Human biological materials from cancer patients are linked directly with public health issues in medical science research as foundational resources so securing "human biological material" is truly important in bio-industry. However, because South Korea's national R and D project lacks a proper managing system for establishing a national standard for the outputs of certain processes, high-value added human biological material produced by the national R and D project could be lost or neglected. As a result, it is necessary to develop a managing process, which can be started by establishing operating guidelines to handle the output of human biological materials. MATERIALS AND METHODS: The current law and regulations related to submitting research outcome resources was reviewed, and the process of data 'acquisition' and data 'distribution' from the point of view of big data and health 2.0 was examined in order to arrive at a method for switching paradigms to better utilize human biological materials. RESULTS: For the deposit of biological research resources, the original process was modified and a standard process with relative forms was developed. With deposit forms, research information, researchers, and deposit type are submitted. The checklist's 26 items are provided for publishing. This is a checklist of items that should be addressed in deposit reports. Lastly, XML-based deposit procedure forms were designed and developed to collect data in a structured form, to help researchers distribute their data in an electronic way. CONCLUSIONS: Through guidelines included with the plan for profit sharing between depositor and user it is possible to manage the material effectively and safely, so high-quality human biological material can be supplied and utilized by researchers from universities, industry and institutes. Furthermore, this will improve national competitiveness by leading to development in the national bio-science industry.

HealthTWITTER Initiative: Design of a Social Networking Service Based Tailored Application for Diabetes Self-Management.

OBJECTIVES: Diabetes is a chronic disease of continuously increasing prevalence. It is a disease with risks of serious complications, thus warranting its long-term management. However, current health management and education programs for diabetes mainly consist of one-way communication, and systematic social support backup to solve diabetics' emotional problems is insufficient. METHODS: According to individual behavioral changes based on the Transtheoretical Model, we designed a non-drug intervention, including exercise, and applied it to a mobile based application. For effective data sharing between patients and physicians, we adopted an SNS function for our application in order to offer a social support environment. RESULTS: To induce continual and comprehensive care for diabetes, rigorous self-management is essential during the diabetic's life; this is possible through a collaborative patient-physician healthcare model. We designed and developed an SNS-based diabetes self-management mobile application that supports the use of social groups, which are present in three social GYM types. With simple testing of patients in their 20s and 30s, we were able to validate the usefulness of our application. CONCLUSIONS: Mobile gadget-based chronic disease symptom management and intervention has the merit that health management can be conducted anywhere and anytime in order to cope with increases in the demand for health and medical services that are occurring due to the aging of the population and to cope with the surge of national medical service costs. This patient-driven and SNS-based intervention program is expected to contribute to promoting the health management habits of diabetics, who need to constantly receive health guidance.

CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

OBJECTIVES: Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. METHODS: Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. RESULTS: In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. CONCLUSIONS: A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

A SWOT Analysis of the Various Backup Scenarios Used in Electronic Medical Record Systems.

OBJECTIVES: Electronic medical records (EMRs) are increasingly being used by health care services. Currently, if an EMR shutdown occurs, even for a moment, patient safety and care can be seriously impacted. Our goal was to determine the methodology needed to develop an effective and reliable EMR backup system. METHODS: Our "independent backup system by medical organizations" paradigm implies that individual medical organizations develop their own EMR backup systems within their organizations. A "personal independent backup system" is defined as an individual privately managing his/her own medical records, whereas in a "central backup system by the government" the government controls all the data. A "central backup system by private enterprises" implies that individual companies retain control over their own data. A "cooperative backup system among medical organizations" refers to a networked system established through mutual agreement. The "backup system based on mutual trust between an individual and an organization" means that the medical information backup system at the organizational level is established through mutual trust. RESULTS: Through the use of SWOT analysis it can be shown that cooperative backup among medical organizations is possible to be established through a network composed of various medical agencies and that it can be managed systematically. An owner of medical information only grants data access to the specific person who gave the authorization for backup based on the mutual trust between an individual and an organization. CONCLUSIONS: By employing SWOT analysis, we concluded that a linkage among medical organizations or between an individual and an organization can provide an efficient backup system.

Proximal risk factors and suicide methods among suicide completers from national suicide mortality data 2004-2006 in Korea.

This study was conducted to examine differences in proximal risk factors and suicide methods by sex and age in the national suicide mortality data in Korea. Data were collected from the National Police Agency and the National Statistical Office of Korea on suicide completers from 2004 to 2006. The 31,711 suicide case records were used to analyze suicide rates, methods, and proximal risk factors by sex and age. Suicide rate increased with age, especially in men. The most common proximal risk factor for suicide was medical illness in both sexes. The most common proximal risk factor for subjects younger than 30 years was found to be a conflict in relationships with family members, partner, or friends. Medical illness was found to increase in prevalence as a risk factor with age. Hanging/Suffocation was the most common suicide method used by both sexes. The use of drug/pesticide poisoning to suicide increased with age. A fall from height or hanging/suffocation was more popular in the younger age groups. Because proximal risk factors and suicide methods varied with sex and age, different suicide prevention measures are required after consideration of both of these parameters.

Comprehensive evaluation of matrix factorization methods for the analysis of DNA microarray gene expression data.

BACKGROUND: Clustering-based methods on gene-expression analysis have been shown to be useful in biomedical applications such as cancer subtype discovery. Among them, Matrix factorization (MF) is advantageous for clustering gene expression patterns from DNA microarray experiments, as it efficiently reduces the dimension of gene expression data. Although several MF methods have been proposed for clustering gene expression patterns, a systematic evaluation has not been reported yet. RESULTS: Here we evaluated the clustering performance of orthogonal and non-orthogonal MFs by a total of nine measurements for performance in four gene expression datasets and one well-known dataset for clustering. Specifically, we employed a non-orthogonal MF algorithm, BSNMF (Bi-directional Sparse Non-negative Matrix Factorization), that applies bi-directional sparseness constraints superimposed on non-negative constraints, comprising a few dominantly co-expressed genes and samples together. Non-orthogonal MFs tended to show better clustering-quality and prediction-accuracy indices than orthogonal MFs as well as a traditional method, K-means. Moreover, BSNMF showed improved performance in these measurements. Non-orthogonal MFs including BSNMF showed also good performance in the functional enrichment test using Gene Ontology terms and biological pathways. CONCLUSIONS: In conclusion, the clustering performance of orthogonal and non-orthogonal MFs was appropriately evaluated for clustering microarray data by comprehensive measurements. This study showed that non-orthogonal MFs have better performance than orthogonal MFs and K-means for clustering microarray data.

Palmatine attenuates osteoclast differentiation and function through inhibition of receptor activator of nuclear factor-κb ligand expression in osteoblast cells.

Osteoclasts are the only cell type capable of resorbing mineralized bone, and they act under the control of numerous cytokines produced by supporting cells such as osteoblasts and stromal cells. Among cytokines, receptor activator of nuclear factor-κB ligand (RANKL) was found to be a key osteoclastogenetic molecule that directly binds to its cognate receptor, RANK, on osteoclast precursor cells. In turn, RANKL, which is an essential factor for differentiation and activation of osteoclasts, is one of the major targets of anti-resorptive agents. In this study, we found that palmatine, an isoquinoline alkaloid originally isolated from Coptis chinensis, had an inhibitory effect on osteoclast differentiation and function in vitro. Palmatine inhibited osteoclast formation in the co-culture system with mouse bone marrow cells (BMC) and osteoblasts in the presence of 10 nM 1α,25-(OH)(2)D(3). Palmatine did not affect osteoclast formation induced by RANKL in the BMC cultures. Reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that palmatine significantly inhibited the expression of 1α,25-(OH)(2)D(3)-induced expression of RANKL mRNAs in stromal cells without loss of cell viability. Moreover, palmatine suppressed resorption pit formation by mature osteoclasts on dentin slices and induced disruption of actin ring formation in mature osteoclasts with an impact on cell viability. Taken together, these results suggest that palmatine attenuates osteoclast differentiation through inhibition of RANKL expression in osteoblast cells, and its inhibitory effect on bone resorption is due to its disruptive effect on actin rings in mature osteoclasts. Therefore, palmatine might be an ideal candidate as an anti-resorptive agent for the prevention and treatment of bone disorders such as osteoporosis.

Alisol-B, a novel phyto-steroid, suppresses the RANKL-induced osteoclast formation and prevents bone loss in mice.

Osteoclasts, bone-resorbing multinucleated cells, are differentiated from hemopoietic progenitors of the monocyte/macrophage lineage. Bone resorption by osteoclasts is considered a potential therapeutic target to the treatment of erosive bone diseases, including osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we found that alisol-B, a phyto-steroid from Alisma orientale Juzepczuk, exhibited inhibitory effects on osteoclastogenesis both in vitro and in vivo. Although RT-PCR analysis showed that alisol-B did not affect the 1alpha,25(OH)(2)D(3)-induced expressions of RANKL, OPG and M-CSF mRNAs in osteoblasts, addition of alisol-B to co-cultures of mouse bone marrow cells and primary osteoblasts with 10(-8)M 1alpha,25(OH)(2)D(3) caused significant inhibition of osteoclastogenesis. We further examined the direct effects of alisol-B on osteoclast precursors. Alisol-B strongly inhibited RANKL-induced osteoclast formation when added during the early stage of cultures, suggesting that alisol-B acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, alisol-B inhibited the phosphorylation of JNK, which are upregulated in response to RANKL in bone marrow macrophages, alisol-B also inhibited RANKL-induced expression of NFATc1 and c-Fos, which are key transcription factors for osteoclastogenesis. In addition, alisol-B suppressed the pit-forming activity and disrupted the actin ring formation of mature osteoclasts. In a hypercalcemic mouse model induced by 2-methylene-19-nor-(20S)-1alpha,25(OH)(2)D(3) (2MD), an analog of 1alpha,25(OH)(2)D(3), administration of alisol-B significantly suppressed 2MD-induced hypercalcemia as resulting from the inhibition of osteoclastogenesis. Taken together, these findings suggest that alisol-B may be a potential novel therapeutic molecule for bone disorders by targeting the differentiation of osteoclasts as well as their functions.

Antimicrobial effect and resistant regulation of Glycyrrhiza uralensis on methicillin-resistant Staphylococcus aureus.

In the present study, we investigated antimicrobial activity of Glycyrrhiza uralensis against various strains of methicillin-resistant Staphylococcus aureus (MRSA) (KCCM 11812, 40510, 40512). Glycyrrhiza uralensis was extracted by 80% MeOH and fractionated by organic solutions. The extract and fractions showed antimicrobial activity against standard S. aureus as well as MRSA. In the minimum inhibitory concentration test, G. uralensis showed 0.25 mg mL(-1) in hexane fraction and 0.10-0.12 mg mL(-1) in chloroform fraction. Especially, chloroform fraction showed 2.5 times higher antimicrobial activity than penicillin. Furthermore, chloroform fraction correlated with MRSA gene expression (MecA, MecI, MecRI, FemA). These results suggest that G. uralensis may have potent antimicrobial activity and thus, this medicinal herb can be a suitable phytotherapeutic agent for treating MRSA infections.