Timosaponin A3 Induces Anti-Obesity and Anti-Diabetic Effects In Vitro and In Vivo.

Obesity is a serious global health challenge, closely associated with numerous chronic conditions including type 2 diabetes. Anemarrhena asphodeloides Bunge (AA) known as Jimo has been used to address conditions associated with pathogenic heat such as wasting-thirst in Korean Medicine. Timosaponin A3 (TA3), a natural compound extracted from AA, has demonstrated potential therapeutic effects in various disease models. However, its effects on diabetes and obesity remain largely unexplored. We investigated the anti-obesity and anti-diabetic properties of TA3 using in vitro and in vivo models. TA3 treatment in NCI-H716 cells stimulated the secretion of glucagon-like peptide 1 (GLP-1) through the activation of phosphorylation of protein kinase A catalytic subunit (PKAc) and 5'-AMP-activated protein kinase (AMPK). In 3T3-L1 adipocytes, TA3 effectively inhibited lipid accumulation by regulating adipogenesis and lipogenesis. In a high-fat diet (HFD)-induced mice model, TA3 administration significantly reduced body weight gain and food intake. Furthermore, TA3 improved glucose tolerance, lipid profiles, and mitigated hepatic steatosis in HFD-fed mice. Histological analysis revealed that TA3 reduced the size of white adipocytes and inhibited adipose tissue generation. Notably, TA3 downregulated the expression of lipogenic factor, including fatty-acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP1c), emphasizing its potential as an anti-obesity agent. These findings revealed that TA3 may be efficiently used as a natural compound for tackling obesity, diabetes, and associated metabolic disorders, providing a novel approach for therapeutic intervention.

Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua Cham. et Schltdl tubers. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrate that ACN inhibited c-Myc expression through CNOT2 and MID1IP1, and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

Momordicae Semen inhibits migration and induces apoptotic cell death by regulating c-Myc and CNOT2 in human pancreatic cancer cells.

Pancreatic cancer(PC) is less common than other cancers; however, it has a poor prognosis. Therefore, studying novel target signaling and anticancer agents is necessary. Momordicae Semen (MS), the seed of Momordica sochinensis Spreng, mainly found in South-East Asia, including China and Bangladesh, is used to treat various diseases because of its anticancer, antioxidant, anti-inflammatory, and antibacterial properties. However, the effect of the MS extract on pancreatic cancer cells remains unknown. In this study investigated whether the MS extract exerted an anti-cancer effect by regulating c-Myc through CNOT2. Cytotoxicity and proliferation were investigated using MTT and colony formation assays. The levels of apoptotic, oncogenic, and migration-associated factors were confirmed using immunoblotting and immunofluorescence. Wound closure was analyzed using a wound healing assay. The chemical composition of the MS methanol extracts was analyzed using liquid chromatography-mass spectrometry. We confirmed that the MS extract regulated apoptotic factors and attenuated the stability of c-Myc and its sensitivity to fetal bovine serum. Furthermore, the MS extract increased apoptosis by regulating c-Myc and CNOT2 expression and enhanced the sensitivity of 5-FU in pancreatic cancer. This study showed that the MS extract is a promising new drug for PC.

Viscum album Induces Apoptosis by Regulating STAT3 Signaling Pathway in Breast Cancer Cells.

In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications.

Euonymus sachalinensis Induces Apoptosis by Inhibiting the Expression of c-Myc in Colon Cancer Cells.

We hypothesized that Euonymus sachalinensis (ES) induces apoptosis by inhibiting the expression of c-Myc in colon cancer cells, and this study proved that the methanol extract of ES has anticancer effects in colon cancer cells. ES belongs to the Celastraceae family and is well known for its medicinal properties. Extracts of species belonging to this family have been used to treat diverse diseases, including rheumatoid arthritis, chronic nephritis, allergic conjunctivitis, rhinitis, and asthma. However, ES has been targeted because there are currently few studies on the efficacy of ES for various diseases, including cancer. ES lowers cell viability in colon cancer cells and reduces the expression of c-Myc protein. We confirm that the protein level of apoptotic factors such as PARP and Caspase 3 decrease when ES is treated with Western blot, and confirm that DNA fragments occur through TUNEL assay. In addition, it is confirmed that the protein level of oncogenes CNOT2 and MID1IP1 decrease when ES is treated. We have also found that ES enhances the chemo-sensitivity of 5-FU in 5-FU-resistant cells. Therefore, we confirm that ES has anticancer effects by inducing apoptotic cell death and regulating the oncogenes CNOT2 and MID1IP1, suggesting its potential for use in the treatment of colon cancer.

Helixor-M Suppresses Immunostimulatory Activity through TLR4-Dependent NF-κB Pathway in RAW 264.7 Cells.

Inflammation causes a protective immune response, which can be observed by examining the inflammatory responses of macrophages. Macrophages release various immunostimulatory factors when destroying external pathogens. We induced lipopolysaccharides (LPS) in RAW 264.7 cells, a macrophage cell line, to determine whether Helixor-M can cause immuno-suppression. Helixor-M is known to have anticancer and immune effects. However, an indicator that regulates immunity has not been clearly confirmed. To this end, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to confirm Helixor-M was not cytotoxic. Western blotting and real-time polymerase chain reaction (RT-PCR) confirmed the anti-inflammatory effects. Additionally, immunofluorescence assay confirmed the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, a representative inflammatory pathway. Helixor-M was found to be non-cytotoxic, induce the NF-κB pathway, and reduce the levels of pro-inflammatory cytokine and mitogen-activated protein kinase (MAPK). We found Helixor-M affected the PI3K/AKT/JNK pathway. Therefore, we confirmed Helixor-M acts as an anti-inflammatory agent through NF-κB, TLR4 and PI3K inhibition and that it could be an effective immunosuppressive drug.

Role of cytochrome P450 2J2 on cell proliferation and resistance to an anticancer agent in hepatocellular carcinoma HepG2 cells.

The present study examined the role of human cytochrome P450 2J2 (CYP2J2) on cell proliferation and resistance to an anticancer agent using stable hepatocellular carcinoma HepG2 cells overexpressing CYP2J2. Overexpression of CYP2J2 significantly increased HepG2 cell proliferation and the expression levels of cell cycle regulatory proteins, including cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4. CYP2J2-overexpressing HepG2 cells exhibited high levels of Akt phosphorylation compared with those observed in wild-type HepG2 cells. Although Akt phosphorylation in both cell lines was significantly attenuated by LY294002, a specific phosphoinositide 3-kinase/Akt signaling inhibitor, the levels of Akt phosphorylation following treatment with LY294002 were higher in CYP2J2-overexpressing HepG2 cells than in wild-type HepG2 cells. Cell counting revealed that proliferation was reduced by LY294002 in both cell lines; however, CYP2J2-overexpressing HepG2 cell numbers were higher than those of wild-type HepG2 cells following treatment with LY294002. These results indicated that increased cell proliferation by CYP2J2 overexpression is mediated by increased Akt activity. It was also demonstrated that doxorubicin, an anticancer agent, reduced cell viability, induced a significant increase in the B-cell lymphoma (Bcl)-2 associated X protein (Bax)/Bcl-2 ratio and decreased pro-caspase-3 levels in wild-type HepG2 cells. However, the doxorubicin-induced reduction in cell viability was significantly attenuated by enhanced upregulation of CYP2J2 expression. The increase in the Bax/Bcl-2 ratio and the decrease in pro-caspase-3 levels were also recovered by CYP2J2 overexpression. In conclusion, CYP2J2 serves important roles in cancer cell proliferation and resistance to the anticancer agent doxorubicin in HepG2 cells.

Purification of small molecule-induced cardiomyocytes from human induced pluripotent stem cells using a reporter system.

In order to realize the practical use of human pluripotent stem cell (hPSC)-derived cardiomyocytes for the purpose of clinical use or cardiovascular research, the generation of large numbers of highly purified cardiomyocytes should be achieved. Here, we show an efficient method for cardiac differentiation of human induced pluripotent stem cells (hiPSCs) in chemically defined conditions and purification of hiPSC-derived cardiomyocytes using a reporter system. Regulation of the Wnt/ß-catenin signaling pathway is implicated in the induction of the cardiac differentiation of hPSCs. We increased cardiac differentiation efficiency of hiPSCs in chemically defined conditions through combined treatment with XAV939, a tankyrase inhibitor and IWP2, a porcupine inhibitor and optimized concentrations. Although cardiac differentiation efficiency was high (>80%), it was difficult to suppress differentiation into non-cardiac cells, Therefore, we applied a lentiviral reporter system, wherein green fluorescence protein (GFP) and Zeocin-resistant gene are driven by promoter activation of a gene (TNNT2) encoding cardiac troponin T (cTnT), a cardiac-specific protein, to exclude non-cardiomyocytes from differentiated cell populations. We transduced this reporter construct into differentiated cells using a lentiviral vector and then obtained highly purified hiPSC-derived cardiomyocytes by treatment with the lowest effective dose of Zeocin. We significantly increased transgenic efficiency through manipulation of the cells in which the differentiated cells were simultaneously infected with virus and re-plated after single-cell dissociation. Purified cells specifically expressed GFP, cTnT, displayed typical properties of cardiomyocytes. This study provides an efficient strategy for obtaining large quantities of highly purified hPSC-derived cardiomyocytes for application in regenerative medicine and biomedical research.

Analysis of vastus lateralis and vastus medialis oblique muscle activation during squat exercise with and without a variety of tools in normal adults.

[Purpose] The present study investigated the effects of squat exercises with and without a variety of tools including a gym ball, wedge, and elastic band on the vastus lateralis and vastus medialis oblique muscles. [Subjects and Methods] A total of twenty healthy subjects with no history of neurological, musculoskeletal injury, or pain in the lower extremities were recruited. All subjects performed four types of exercise (conventional squat exercise, squat exercise with a gym ball, squat exercise with a wedge, squat exercise with an elastic band). [Results] There were no significant differences between exercises in comparison of the vastus lateralis muscle activity. In the squat exercise with a wedge, significantly higher activity of the vastus medialis oblique muscle was found compared with in the squat exercise with an elastic band. [Conclusion] The present study suggests that the conventional squat exercise can be one of the useful interventions for patients with patellofemoral pain syndrome.

The Postnatal Care Experiences among First Time Chinese Immigrant Mothers Living in Korea.

PURPOSE: This study was to explore the postnatal care experiences among first time Chinese immigrant mothers living in Korea. METHODS: Data were collected by focus group interviews with 12 first time Chinese immigrant mothers utilizing 3 focus groups. After obtaining written informed consent from all participants, each session of the focus group was audio-recorded and transcribed verbatim. Data were analyzed by content analysis to identify major themes. RESULTS: Four major themes for postnatal care experiences were extracted from the data as follows. 1) Range over traditional, modern, Korean or Chinese postnatal care, 2) Struggle with newborn care, 3) Another struggle with breastfeeding, and 4) Difficulties in becoming a mother as an immigrant. CONCLUSION: Based on their postpartum care experiences, it is concluded that participants requested more professional practical and individualized education/training for successful breastfeeding and newborn care. Health care providers need to develop and implement integrated support and mentoring programs that include information and peer support system for the first time Chinese immigrant mothers living in Korea. This would decrease the difficulties of becoming a mother.

Systematic Review of Quantitative Research related to Maternal Adaptation among Women Immigrants by Marriage in Korea.

PURPOSE: This study aimed to describe knowledge status of current research related to maternal adaptation of women immigrants by marriage in Korea. METHODS: Eighteen quantitative current researches published from January, 2006 to August, 2014 that met the inclusion and exclusion criteria. These 18 articles finally selected for systemic review from 5,168 articles. All current researches included the mother within one year after childbirth and one variable related to maternal adaptation at least. RESULTS: Variables related to psychological adaptation (48.1%) were mostly studied. In detail, parenting stress (17.3%) and parenting competency (15.4%) were frequently surveyed. Also, social support (7.7%), husband rearing support (5.8%) of relational adaptation, and acculturation (3.8%) of cultural adaptation were importantly studied. In addition, frequently used instruments for each study variable were analyzed and evaluated. As major results, parenting stress and parenting efficacy were significantly influenced by social support or husband rearing support and acculturation, and had an effect on parenting behaviors. Various maternal education programs were effective in improving maternal role confidence or parenting efficacy and decreasing parenting stress. CONCLUSION: Nursing intervention programs for improving maternal adaptation should focus on decreasing parenting stress and increasing parenting efficacy by improving social support and acculturation level of women immigrants by marriage in Korea.

Empirical test of an explanatory theory of postpartum fatigue in Korea.

AIM: This paper is a report of a study designed to test an explanatory theory of postpartum fatigue. BACKGROUND: Postpartum fatigue is influenced by various factors and affects a mother's performance. A full understanding of postpartum fatigue is very important for developing effective nursing strategies to reduce postpartum fatigue and enhance mothers' performance. METHODS: Healthy postpartum women were recruited from five medical centers and one midwifery office in urban area in Korea (n = 291) by convenience sampling. Data were collected at 4- to 8-week follow-up visits after childbirth in 2006, using a self-report questionnaire. The proposed fatigue theory incorporated postpartum fatigue, postpartum depression, sleep quality, childcare stress, unsatisfactory feeding, social support, infant difficulty and satisfaction with Sanhujori, the Korean traditional postpartum care provided for 3 weeks following delivery by non-professional caregivers. Structural equation modelling was used to test the explanatory theory of postpartum fatigue. RESULTS: The modified fatigue theory showed good fit and high compatibility with the empirical data. In the final explanatory theory, postpartum depression and sleep quality directly affected postpartum fatigue, while childcare stress and the cultural phenomenon of Sanhujori had indirect effects on postpartum fatigue, via postpartum depression and sleep quality respectively. CONCLUSION: These findings suggest the potential role of comprehensive nursing focused on decreasing postpartum depression and improving sleep quality as a way to decrease postpartum fatigue. Also, nursing strategies for decreasing childcare stress and enhancing Sanhujori satisfaction may be helpful in reducing postpartum fatigue in Korean mothers.

Effects on Nursing Students of Cognition-Behavior Integrated Breast Cancer Prevention Education Using an Interchangeable Nodule Model.

PURPOSE: The study was done to examine the effects of cognition-behavior integrated breast cancer prevention education, in which a breast model with interchangeable nodules was utilized, on the self-competency of nursing students in performing breast cancer education. METHODS: A nonequivalent control group non-synchronized design was used. A traditional lecture intervention was provided for 49 3rd year college of nursing students (control group) while the integrated breast cancer prevention education was given to 47 3rd year students in the same college one year later (experimental group). The integrated breast cancer prevention education was developed by the research team to strengthen the competency of cognitive and behavioral components in education on breast cancer. RESULTS: Effects of the intervention were found to be significant through all study variables: knowledge about breast cancer (t=7.79, p <.001), breast cancer risk awareness (t=2.05, p <.05), self-competency of breast self-exam (t=8.27, p <.001), and intention to teach breast self-exam (t=3.87, p <.001). CONCLUSION: The integrated breast cancer prevention education was useful to improve not only knowledge about breast cancer but competency in performing breast examination for nursing students who acquired technical skills from various simulation nodules. As the program helped the students to be prepared as confident educators, future application of the module is recommended for academic curricula.

[Women's cancer screening according to Body Mass Index in a cohort of rural Korean women].

PURPOSE: This study was done to examine the difference in cancer screening with mammography and Papanicolaou smear according to Body Mass Index (BMI). METHODS: The participants in this study were 5,912 women ages 40 to 69 yr, selected from the Korean Genomic Regional Cohort in Kangwon province. Mammography and Papanicolaou smear were assessed by questionnaire and body weight (kg) and height (m) measured to calculate BMI. RESULTS: The distribution of BMI was as follows: low weight (1.5%), normal weight (31.1%), over weight (24.6%), mildly obese (36.4%) and severely obese (6.3%). After adjusting for age, education and monthly income, compared with normal weight women, overweight women (odds ratio [OR]=1.283, 95% confidence interval [CI]=1.089-1.513) and mildly obese women (OR=1.214, 95% CI=1.048-1.406) were less likely to have had mammography. In contrast to mammography, cancer screening with Papanicolaou smear was not significantly different by BMI. CONCLUSION: Obese women in rural areas are less likely to screen for breast cancer by using mammography than non obese women. To ensure regular screening for breast cancer, health care providers need to give scrupulous care to obese women and remove barriers originated from obesity. Also, educational and clinical implications are considered to increase the Papanicolaou smear rate.

Compression of the left ventricular outflow tract during cardiopulmonary resuscitation.

OBJECTIVES: This prospective observational study was performed to investigate if the hand position used for external chest compressions is in an optimal position for compressing the ventricles during standard cardiopulmonary resuscitation (CPR). METHODS: Transesophageal echocardiography (TEE) was performed during standard CPR in 34 patients with nontraumatic cardiac arrest (24 males, mean +/- standard deviation [SD] age = 56 +/- 12 years). On the recorded image of TEE, an area of maximal compression (AMC) was identified, and the degree of compression at the AMC and the left ventricular stroke volume was calculated. RESULTS: A significant narrowing of the left ventricular outflow tract (LVOT) or the aorta was noted in all patients, with the degree of compression at the AMC ranging from 19% to 83% (mean +/- SD = 49 +/- 19%). The AMC was found at the aorta in 20 patients (59%) and at the LVOT in 14 patients (41%). A significant narrowing of more than 50% of the diameter at the end of the relaxation phase occurred in 15 patients (44%). On linear regression, the left ventricular stroke volume was correlated with the location of the AMC (R(2) = 0.165, p = 0.017). CONCLUSIONS: The outflow of the left ventricle is affected during standard CPR, resulting in varying degrees of narrowing in the LVOT and/or the aortic root.

Myocardial perfusion defects and coronary risk factors in symptomatic and asymptomatic elderly women.

BACKGROUND: We investigated the relation between risk factors of coronary artery disease (CAD) and myocardial ischemia detected by (201)Tl SPECT in elderly women. METHODS: 306 women aged >or=75 yr (79.1 +/- 3.6 yr) who underwent pharmacologic (201)Tl SPECT for suspected CAD based on symptoms or CAD risk factors were included. Coronary risk factors were evaluated by medical records, and included diabetes mellitus (DM), hypertension, hypercholesterolemia, cigarette smoking, greater age (>or=80 yr), and obesity. Summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were calculated based on stress and redistribution SPECT images for semi-quantification. RESULTS: The symptomatic group (n = 110) had a 34.5% perfusion defect rate. The asymptomatic group (n = 196) had a significantly lower perfusion defect rate of 16.8%. However, this significantly increased to 29.4% and 22.0% in the presence of diabetes mellitus (DM) and hypertension, respectively. In addition, the summed stress score of asymptomatic patients (12.4 +/- 6.0) was not lower but comparable to that of symptomatic patients (10.0 +/- 6.0). CONCLUSIONS: In elderly women suspected of CAD, pharmacologic perfusion imaging can be used to identify myocardial ischemia in patients with angina as well as asymptomatic subjects with concurrent DM or hypertension.

Activity intolerance and impaired physical mobility in elders.

PURPOSE: To clarify the use of two nursing diagnoses, activity intolerance and impaired physical mobility, with elderly patients. METHOD: Ninety-two elders from a long-term care facility in Wonju, Korea. A checklist developed by the researchers was used for data collection. FINDINGS: Defining characteristics from this study related to psychological components of activity intolerance are significant in differentiating between the two diagnoses. Using a decision-making tree based on data from this study, each nursing diagnosis can be correctly identified. CONCLUSIONS: The results of this study are significant in broadening the defining characteristics to be used in differentiating between two nursing diagnoses. PRACTICE IMPLICATIONS: Clarification of nursing diagnoses serves to direct students and nurses to choosing appropriate interventions.

Predictors of mammography participation among rural Korean women age 40 and over.

PURPOSE: The study was conducted to identify predictors of mammography screening for rural Korean women according to 'Stage of Change' from the Transtheoretical Model which, along with the Health Belief Model, formed the theoretical basis for this study. METHODS: A cross-sectional descriptive design was utilized. Through convenience sampling 432 women were selected from 2 rural areas. Data were collected by survey. Health beliefs constructs were measured with Champion's HBM Scale-Korea version. Mammography participation was measured using the Stage of Mammography Adoption Scale developed by Rakowski, et al. (1992). RESULTS: The most frequent stage of mammography adoption was 'contemplation' (40.5%). Predictors of stage of mammography adoption included 'mammogram recommended by health professional' (beta=0.59, t=16.12, p=.000), 'perceived benefits' (beta=0.09, t=2.21, p=.050), 'perceived susceptibility' (beta=0.09, t=1.98, p=.050), and 'perceived barriers' (beta= 0.07, t= -2.05, p=.041). 'Mammogram recommended by health professional' demonstrated the greatest association with having a mammogram. CONCLUSION: Health professionals play key roles in improving mammography participation and should recognize the importance of their role in cancer prevention and be more actively involved in education and counseling on prevention of breast cancer.

[Content analysis of the experience of preceptors in clinical education for senior student nurses].

PURPOSE: The purpose of this study was to identify experiences of nurses who served as preceptors in clinical education for senior student nurses in a college of medicine in Wonju city. METHOD: Data was collected from 20 preceptors instructing senior student nurses in 2001 using a self-completion questionnaire. To analyze data, content analysis was done using an analysis scheme developed by the investigators. RESULT: The analysis scheme consisted of 7 categories and 25 subcategories. 135 significant statements were analyzed and categorized. Preceptors indicated that they were role models, socialization facilitators and educators while instructing students in the clinical practicum. In performing the preceptors' role, preceptors reported that their most important change was self-enhancement,and positive experience was a constructive work atmosphere. The most important factor facilitating the preceptors' role performance was support from head nurses, and the most discouraging factor was work loads. CONCLUSION: This study suggests that interventions for encouragement and socialization of preceptors should be developed to promote clinical education for senior student nurses.