Comparing factors related to perceived control and preventive behaviors from COVID-19 between Japanese and American nursing students: A cross-sectional study.

AIM: Higher levels of perceived control are important to maintain health. The difference in factors related to perceived control and preventive behaviors during the COVID-19 pandemic between Japanese and American nursing students remains unknown. This study aimed to compare factors related to perceived control and infection preventive behaviors between the two countries. METHODS: This cross-sectional study included nursing students attending four universities in Japan and one in the United States. Using Google Forms, the participants answered a survey comprising sociodemographic data, the Perceived Control and Self-Efficacy Scale, the Perceived Health Competence Scale, and a preventive behavior questionnaire. The data were collected from November 2020 to May 2021. Linear and logistic regressions were used to analyze the factors related to perceived control and preventive behaviors, respectively. RESULTS: Data from 878 students were analyzed. University/campus emerged as a strong predictor for perceived control and preventive behaviors in both countries, with a positive correlation between perceived control and preventive behaviors. Older age, less frequent alcohol consumption, higher perceived health competence, less frequent work in Japan; and chronic conditions in the United States were associated with frequent preventive behaviors. Younger age was correlated with higher perceived control in Japan, while religion and increased workload were potential factors for American students. CONCLUSION: Individual factors were pivotal in Japan, whereas interpersonal factors were more likely related to perceived control in the United States. Additionally, in both countries, policy or organizational factors significantly influenced students' preventive behaviors.

Cross-sectional study of factors related to COVID-19 vaccination uptake among university healthcare students.

Introduction: Healthcare students are more likely to become infected than other university students as they may encounter patients with COVID-19 during clinical training. Vaccination uptake is essential to prevent infection. This study explored factors related to COVID-19 vaccination uptake among healthcare students. Methods: This cross-sectional study conducted online surveys of undergraduate and graduate nursing and healthcare graduate students from four medical universities in the Tokyo Metropolitan Area of Japan. Data were collected from June to August 2022, when the fourth vaccination program was initiated. Results: Data from 1,169 students were analyzed (response rate = 37.3%). The mean age was 25.1 ± 7.6 years, and most were female (82.3%). Academic majors included nursing (68.0%), medicine (16.3%), dentistry (9.3%), and others (6.4%). Thirty students (2.6%) were not vaccinated, one student (0.1%) had received one vaccination, 997 (85.3%) had received three, and 27 (2.3%) had received four. The major reason for not being vaccinated was insufficient confirmation of its safety (n = 25). Students who had received at least one vaccination (n = 1,139), 965 (84.7%) reported experiencing adverse side effects, the most frequent being pain at the injection site (76.2%), followed by fever (68.3%). In the logistic regression, a greater number of vaccinations (3-4 times) was associated with older age (odds ratio, OR = 1.53), working (OR = 1.67), and more frequent infection-preventive behaviors (OR = 1.05). Significantly fewer students were vaccinated at University B than at University A (OR = 0.46). Additionally, those majoring in subjects other than nursing (OR = 0.28), and students from non-Asian countries (OR = 0.30) were less likely to be vaccinated. Discussion: It is necessary to pay attention to and encourage the vaccination of students who engage in low levels of preventive behavior, students who are young, international, or unemployed, and those in non-healthcare professional majors.

Enhancing intercultural sensitivity in Japanese nursing students through international online nursing courses: A quasi-experimental study.

BACKGROUND: Globalization has highlighted the importance of being competent in communicating with people of various cultural backgrounds. PURPOSE: To evaluate the effect of international courses for nursing students through online education in terms of intercultural sensitivity and perceived English proficiency. DESIGN: A one-group pretest-posttest quasi-experimental design with an online self-reported questionnaire was conducted. PARTICIPANTS AND SETTINGS: Participants were second-, third-, and fourth-year nursing students at a medical university in Tokyo in the spring term of 2021. METHOD: Measurements were performed before and after the international nursing courses, which consisted of 1) nursing communication English, taught by native English instructors to second- and third-year students; and 2) international health nursing, taught by overseas-experienced faculty members to fourth-year students. Furthermore, there is an elective Collaborative Online International Learning course, where students discuss, collaborate, and complete common assignments with students from a university in the United States. Intercultural sensitivity was measured using the Japanese version of the Intercultural Sensitivity Scale. The pre- and post-test intercultural sensitivity were compared using a paired t-test. Content analysis was employed to analyze the open-ended questions. RESULTS: A total of 104 students' data were analyzed. Students' intercultural sensitivity mean improved significantly from 79.88 ± 8.47 (pre) to 83.04 ± 8.63 (post). Participants in the elective course (n = 7) showed significantly higher intercultural sensitivity levels than non-participants. The self-evaluated English proficiency of second- and third-year students who took English courses significantly improved after the courses. Themes extracted by elective course participants revealed students' perceptions toward learning about diverse cultures, resilience, and intercultural communication skills, which they can utilize for nursing practice in the future. CONCLUSION: Taking international nursing courses can increase nursing students' intercultural sensitivity. Universities are encouraged to provide international nursing courses to help enhance their cultural sensitivity and competency for their future nursing careers.

The Impact of Collaborative Online International Learning on Intercultural Sensitivity Among Nursing Students in the United States and Japan.

ABSTRACT: Collaborative online international learning (COIL) is a curricular approach that allows students to collaborate across cultures using various communication technologies. Little is known about the influence of COIL on intercultural sensitivity, a key competency for nursing students to better serve increasingly diverse patient populations. We implemented COIL in undergraduate nursing courses in the United States and Japan and examined its impact on intercultural sensitivity using the Intercultural Sensitivity Scale (ISS) as a pretest and posttest. The results of a paired t -test indicated ISS total scores significantly increased after COIL, supporting its use in nursing education courses.

Relationship Between Resilience and Perceived Control After Acute Coronary Syndrome: A Prospective Study.

BACKGROUND: Patients with acute coronary syndrome report poor health-related quality of life and decreased levels of perceived control. Perceived control is a person's belief that they can cope with negative events. Resilience is an adaptation that gives people the capacity to recover from difficult situations, and higher levels of resilience may impact recovery after an acute event. OBJECTIVE: The aim of this study was to analyze the relationship between resilience, perceived control, and health outcomes of patients hospitalized with acute coronary syndrome within 6 months of discharge. METHODS: Data were collected prospectively from adult patients hospitalized with acute coronary syndrome in 3 university hospitals in the Tokyo Metropolitan area, Japan. All data were collected between December 2015 and December 2019. The Sukemune-Hiew Resilience Test (part 1) was used to measure resilience, which includes 3 domains of social support, self-efficacy, and sociality. The Control Attitudes Scale-Revised was used to measure perceived control. Linear regression and path analysis were used to statistically analyze the relationship among variables. RESULTS: Higher resilience, especially self-efficacy, was associated with higher perceived control during admission. Higher resilience, especially social support, during admission was associated with perceived control at 6 months after adjusting for income and education. Higher resilience during admission was associated with better perceived control at 3 months, which was associated with better health outcomes at 6 months. Higher income and lower depression were related to higher resilience. CONCLUSIONS: Nurses should make sure patients with depression, low income, and low social support are connected with appropriate treatment and social support resources.

A Case Report of Collaborative Online International Learning in Nursing and Health Studies Between the United States and Japan.

ABSTRACT: Collaborative online international learning (COIL) is an innovative and cost-effective pedagogy to develop cross-cultural awareness through digital technology across shared multicultural learning environments. We implemented our first COIL virtual exchange for undergraduate students at universities in the United States and Japan. We used Padlet for asynchronous discussions to build rapport among students at each institution and Zoom for synchronous discussions to deliver oral presentations. Feedback from students indicate an overall increase in intercultural competence and cultural sensitivity. COIL can provide meaningful, affordable, and feasible health education that enhances cultural understanding through virtual exchange.

Factors related to mental health effect among nursing students in Japan and the United States during the coronavirus pandemic: A cross-sectional study.

In the context of mental health, university students have been considered a vulnerable population. However, limited studies have underscored the association between preventive health behaviour levels and mental health effects among nursing students. The current cross-sectional study provides a comparative analysis of the impact of mental health factors on nursing students in Japan and the United States (US) in the context of the coronavirus disease 2019 (COVID-19) pandemic. The study consisted of 878 participants, comprising both undergraduate and graduate nursing students from four universities in Japan, and one from the US. Hierarchical logistic regression was used to analyse the participant data in this study. In contrast to the American students, the Japanese students demonstrated significantly lower levels of perceived control and significantly higher levels of preventive health behaviours. Furthermore, Japanese students exhibited significantly higher levels of stress and/or symptoms of depression induced by the social distancing orders compared to the American students (z = -4.218, P < 0.001). However, no difference was observed after adjusting for perceived control, individual factors, socio-economic factors, and preventive behaviours. During the pandemic, risk factors that can worsen mental health among the nursing students included younger age [odds ratio (95%CI) = 0.62 (0.48-0.81)], women [OR = 2.17 (1.02-4.61)], higher preventive health behaviour [OR = 1.05 (1.02-1.08)], lower perceived control [OR = 0.97 (0.94-0.99)], and lower perceived health competence [OR = 0.93 (0.90-0.96)]. Thus, this study recommends establishing training programmes that enhance perceived control and perceived health competence while encouraging preventive behaviour to support the mental health of nursing students, particularly young female students.

Healthcare graduate students' perceived control and preventive behavior for COVID-19 in Japan and the United States: A cross-sectional study.

Background: Both individual and policy level perceived control are known to be positively related to preventive behavior, and both may differ among healthcare graduate students with different cultural backgrounds. This study compared the preventive health behavior and perceived control among domestic and international healthcare graduate students in Japan and the United States during the COVID-19 pandemic, and analyzed factors associated with preventive health behavior and perceived control. Methods: The study used a self-administered online survey, conducted at two universities in Japan and one university in the United States. The survey included sociodemographic data and scales of preventive health behaviors, perceived control (policy level), and perceived health competence (individual level). Association among variables were analyzed using structural equation modeling. Results: A total of 610 students (485 domestic and 125 international) in Japan and 231 students (220 domestic and 11 international) in the United States completed the survey. Participants' average age was 31.3 years, and 67.0% were female. Model fit of structural equation modeling was good (χ2 = 9.419, P = 0.151, comparative fit index = 0.995, RMSEA = 0.026). Japanese students had better preventive health behavior than American (ß = -0.407, P < 0.001) and international students in both countries (ß = -0.112, P < 0.001). However, Japanese students had significantly lower perceived control than American students (ß = 0.346, P < 0.001) and international students in both countries (ß = 0.188, P < 0.001). Overall higher perceived control (ß = 0.175, P < 0.001) and being female (ß = 0.141, P < 0.001) were significantly associated with better preventive behavior. Although higher perceived control was related to higher perceived health competence (ß = 0.295, P < 0.001), perceived health competence was not associated with preventive behavior (ß = 0.025, P = 0.470). Religion was not associated with perceived control or preventive behavior. Conclusion: Nationality was identified as the main factor associated with both perceived control and preventive behavior. Policy level perceived control was more strongly associated with preventive health behavior than individual level perceived health competence. Further investigations in the contribution of specific cultural dimensions associated with perceived control and preventive behaviors are recommended.

Pathological variants in genes associated with disorders of sex development and central causes of hypogonadism in a whole-genome reference panel of 8380 Japanese individuals.

Disorders of sex development (DSD) comprises a congenital condition in which chromosomal, gonadal, or anatomical sex development is atypical. In this study, we screened for pathogenic variants in 32 genes associated with DSDs and central causes of hypogonadism (CHG) in a whole-genome reference panel including 8380 Japanese individuals constructed by Tohoku Medical Megabank Organization. Candidate pathogenic (P) or likely pathogenic (LP) variants were extracted from the ClinVar, InterVar, and Human Gene Mutation databases. Ninety-one candidate pathological variants were found in 25 genes; 28 novel candidate variants were identified. Nearly 1 in 40 (either ClinVar or InterVar P or LP) to 157 (both ClinVar and InterVar P or LP) individuals were found to be carriers of recessive DSD and CHG alleles. In these data, genes implicated in gonadal dysfunction did not show loss-of-function variants, with a relatively high tendency of intolerance for haploinsufficiency based on pLI and Episcore, both of which can be used for estimating haploinsufficiency. We report the types and frequencies of causative variants for DSD and CHG in the general Japanese population. This study furthers our understanding of the genetic causes and helps to refine genetic counseling of DSD and CHG.

Perceived Control, Preventative Health Behaviors, and the Mental Health of Nursing Students During the COVID-19 Pandemic: A Cross-Sectional Study.

Introduction: Perceived control is an individual's subjective beliefs about the amount of control he or she has over the environment or outcome. Objective: To examine the relationship between perceived control, preventive health behaviors, and mental health effects of undergraduate nursing students during the COVID-19 pandemic. Methods: This cross-sectional correlational study used online self-administered questionnaires. Participants were nursing students attending 3 universities in Tokyo, Japan. Relationships among variables were quantitatively analyzed using linear regressions and a structural equation modeling after adjusting for demographic factors. Results: A total of 557 students participated in the survey. The analysis indicated that higher levels of perceived control were significantly related to higher levels of preventive health behaviors. Although higher preventive health behaviors were related to negative mental health effects, higher levels of perceived health competence translated to improved mental health effects. Perceived control was not directly related to mental health effects but positively related to perceived health competence. Long work hours per week and short hours of sleep per day were associated with lower preventive health behaviors. There were significant differences in the levels of perceived control and preventive health behaviors among students at the 3 universities. Discussion: To improve health behaviors and health competence and subsequently alleviate the mental health effects caused by strictly adhering to recommended health behaviors, students may be supported by the strategies that increase their perceived control. In addition to institutional support, students also require adequate sleep and financial stability to help prevent infections while protecting their mental health.

Factors related to perceived control and health-related quality of life of patients after acute coronary syndrome during admission and after discharge.

AIM: To explore the relationship between demographic factors, acute coronary syndrome-related factors, perceived control and health-related quality of life during admission, 3 months and 6 months after discharge, in patients with acute coronary syndrome. METHODS: Participants were recruited for this longitudinal study after admission for acute coronary syndrome in three university hospitals in the Tokyo metropolitan area, Japan. Self-administered questionnaires included demographic data, perceived control, health-related quality of life, acute coronary syndrome symptoms, fatigue, depression and anxiety. RESULTS: Participants (N = 137) had an average age of 62.8 (SD 11.6) years and 80.3% were male. As a result of Path analysis, higher perceived control (ß = 0.258, p = .001), lower anxiety (ß = -0.226, p = .009) and lower fatigue (ß = -0.231, p = .010), were significantly related to better health-related quality of life (General health). Only annual income was significantly related to perceived control (ß = 0.187, p = .029). Eighty-two (59.9%) participants at 3 months and 54 (39.4%) participants at 6 months completed the questionnaires. Perceived control (F = 7.074, p = .001) and General health (χ2 = 10.22, p = .006) significantly increased over the 6 months. Perceived control during admission was significantly related with health-related quality of life at 3 months. Perceived control at 3 months was significantly related with health-related quality of life at 6 months. CONCLUSION: Perceived control was an important factor for health-related quality of life of the Japanese patients with acute coronary syndrome. It is necessary to investigate whether nursing interventions to enhance perceived control lead to improvement of health-related quality of life.

Identification of sleep hypoventilation in young individuals with Becker muscular dystrophy: A pilot study.

AIM: To report on sleep hypercapnia in Becker muscular dystrophy (BMD) at earlier stages than ever recognized. SUBJECTS AND METHODS: This retrospective study examined nocturnal hypercapnia in six young Becker muscular dystrophy (BMD) patients with deletions of one or more exons of DMD gene. Clinical information, consecutive data on forced vital capacity (FVC%), forced expiratory volume in one second (FEV1%), peak expiratory flow (PEF%), peak cough flow (PCF), average PCO2 in all-night monitoring, and left ventricular ejection fraction (LVEF) were reviewed. RESULTS: In five BMD patients, including three who were still ambulant, nocturnal average PCO2 was elevated to >45 mmHg at 12-31 years of age. Noninvasive positive pressure ventilation was initiated in four patients. Gradual declines in FVC% and PEF% were evident in one BMD patient with exon 3-7 deletion, whereas these functions did not change in the remaining BMD patients. PCF, FEV1%, and LVEF were less informative for the assessment of respiratory function in this patient series. CONCLUSION: Sleep hypercapnia was present in certain BMD patients, which was unexpected from the routine pulmonary function tests. Individualized assessment of nocturnal PCO2, partly based on the deletion types, should be further explored in the clinical practice of BMD patients.

Cerebellar Ganglioglioma in Childhood: Histopathologic Implications for Management During Long-term Survival: A Case Report.

We report the case of a 19-year-old female with cerebellar ganglioglioma that was diagnosed at 4 years of age. Despite treatment with partial resection, radiation, and chemotherapy, residual tumor slowly expanded into the brainstem and upper cervical cord, resulting in nocturnal hypopnea, progressive tetraparesis, and feeding difficulty during 8-10 years of age. Initiation of temozolomide and bevacizumab was effective in preventing further expansion of the tumor, and the patient has been treated at home and in school with noninvasive positive pressure ventilation and gastrostomy. Histopathologic examination of the resected tumor tissue revealed phospho-S6-positive tumor cells of either neuronal or astroglial appearance. This suggests that a higher proportion of cells of glial lineage could be linked to the progression of cerebellar ganglioglioma in childhood. Possible treatment options with mammalian target of rapamycin inhibitors are discussed.

Effectiveness of ethinylestradiol/drospirenone for premenstrual symptoms in Japanese patients with dysmenorrhea: Open-label pilot study.

AIM: A combined oral contraceptive containing ethinylestradiol 20 µg plus drospirenone 3 mg (EE20 + DRSP) in a 24/4 regimen has been shown to alleviate the symptoms of premenstrual syndrome and premenstrual dysphoric disorder. This study was conducted to evaluate the efficacy of EE20 + DRSP in Japanese patients with premenstrual symptoms. MATERIAL AND METHODS: A multicenter, prospective, open-label, single-arm, phase IV study was performed in Japanese women with dysmenorrhea and premenstrual symptoms. They were treated with EE20 + DRSP to alleviate the symptoms of dysmenorrhea for six treatment cycles. Premenstrual symptoms were evaluated using a Premenstrual Symptoms Questionnaire at baseline and after three and six cycles of EE20 + DRSP. The degree of dysmenorrhea was also evaluated using a visual analog scale at baseline and after one, three, and six cycles of EE20 + DRSP. RESULTS: Forty-eight patients were treated with EE20 + DRSP. Most of the premenstrual symptoms were alleviated significantly by three and six cycles of EE20 + DRSP treatment. EE20 + DRSP treatment significantly improved the severity of premenstrual symptoms. We also confirmed the effectiveness of EE20 + DRSP for the treatment for dysmenorrhea. CONCLUSION: This study showed that EE20 + DRSP could be a useful treatment strategy for premenstrual symptoms in Japanese women.

Relationship between admission day and timing of surgery for patients with hip fracture.

AIM: This study investigated: (i) the relationship between admission day of the week and the timing of surgery; (ii) whether the admission day of the week predicted length of stay or patients' outcomes; and (iii) the relationship between the timing of surgery and mortality. METHODS: This was a retrospective, observational study of two community general hospitals in Japan. The inclusion criteria were patients aged 65 years or older who had experienced a hip fracture and undergone surgery during April 2007 to March 2011. Data on demographics, care processes, and health outcomes during hospital stays were collected from hospital records. A questionnaire was sent to patients and/or their family members about the patients' health outcomes after discharge from hospital for hip fracture surgery. RESULTS: Data were collected from a total of 714 patients. In both hospitals, orthopedic surgery was not scheduled every day, and the admission day was significantly related to the timing of surgery. In hospital 1, the admission day explained 38.1% of the variance in the timing of surgery, and in hospital 2, it explained 8.3%. The admission day with early surgery predicted an early discharge. The admission day with delayed surgery predicted better survival. There was no significant relationship between the timing of surgery and mortality in either hospital. CONCLUSION: Earlier surgery, by daily operations, may reduce the length of hospital stays, but its effect on patient outcome remains unclear. It is necessary to carefully determine which patients will benefit from earlier surgery.

Curcumin targets the AKT-mTOR pathway for uterine leiomyosarcoma tumor growth suppression.

BACKGROUND: Uterine leiomyosarcomas generally do not respond well to standard chemotherapy. We previously demonstrated that curcumin, the active ingredient derived from the herb Curcuma longa, inhibits uterine leiomyosarcoma cells in vitro via the inhibition of the AKT-mammalian target of rapamycin (mTOR) pathway. As a preclinical investigation, we performed an in vivo study using female nude mice to confirm the therapeutic potential of curcumin against uterine leiomyosarcoma. METHODS: Human leiomyosarcoma cells, SK-UT-1, were inoculated in female nude mice to establish subcutaneous tumors. Either vehicle control or 250 mg/kg curcumin was administered intraperitoneally every day for 14 consecutive days, and the mice were then killed. The tumors were measured every 2-3 days. The tumors were processed for immunohistochemical analyses to detect total AKT, phosphorylated AKT, total mTOR, phosphorylated mTOR, and phosphorylated S6. To detect apoptosis, the tumors were stained for cleaved PARP and TUNEL. Ki-67 immunohistochemistry was performed to determine cell viability of the tumors. RESULTS: Compared with the control, curcumin reduced uterine leiomyosarcoma tumor volume and mass significantly with a concordant decrease in mTOR and S6 phosphorylation. However, AKT phosphorylation was not significantly altered. Cleaved PARP and TUNEL staining increased significantly with curcumin administration, indicating the induction of apoptosis. There was no difference in Ki-67 staining between the two groups. CONCLUSION: Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by targeting the AKT-mTOR pathway for inhibition.

Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells.

OBJECTIVE: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells. METHODS: Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP). RESULTS: Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase 1/2 pathway and curcumin-induced autophagy. CONCLUSIONS: These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.

Dietary intake of nutrients with adequate intake values in the dietary reference intakes for Japanese.

The Adequate Intake (AI) values in the Dietary Reference Intakes for Japanese (DRIs-J) 2010 were mainly determined based on the median intakes from 2 y of pooled data (2005-2006) from the National Health and Nutrition Survey-Japan (NHNS-J). However, it remains unclear whether 2 y of pooled data from the NHNS-J are appropriate for evaluating the intake of the population. To clarify the differences in nutrient intakes determined from 2 and 7 y of pooled data, we analyzed selected nutrient intake levels by sex and age groups using NHNS-J data. Intake data were obtained from 64,624 individuals (age: ≥1 y; 47.4% men) who completed a semi-weighed 1-d household dietary record that was part of the NHNS-J conducted annually in Japan from 2003 to 2009. There were no large differences between the median intakes calculated from 2 or 7 y of pooled data for n-6 or n-3 polyunsaturated fatty acids (PUFAs), vitamin D, pantothenic acid, potassium, or phosphorus. When the AI values and median intakes were compared, there was no large difference in the values for n-6 or n-3 PUFAs, pantothenic acid, or phosphorus. Conversely, the AI values for vitamin D and potassium differed from the median intakes of these nutrients for specific sex and age groups, because values were not based on NHNS-J data. Our results indicate that 2 y of pooled data from the NHNS-J adequately reflect the population's intake, and that the current system for determination of AI values will be applicable for future revisions.

The antidiabetic drug metformin inhibits uterine leiomyoma cell proliferation via an AMP-activated protein kinase signaling pathway.

Uterine leiomyomas are the most common gynecological benign tumors and greatly affect reproductive health and wellbeing. Metformin is the most widely used antidiabetic drug in the world, and there is increasing evidence of a potential efficacy of this agent as an anticancer drug. In order to understand metformin's anti-tumorigenic potential better, in this study, we investigated the inhibitory effect of metformin and expression of key targets of metformin cell signaling in leiomyoma cells. Cell proliferation was assessed after exposure to metformin. Apoptosis was assessed by western blotting for cleaved-PARP and TUNEL staining. The expressions of phosphorylated AMPK and phosphorylated S6 were determined by western blotting. Metformin potently inhibited ELT-3 cell proliferation in a dose-dependent manner. Western blotting analysis demonstrated that metformin induced phosphorylation of AMPK and the inhibitory effect was attenuated with AMPK inhibitor, compound C. In parallel, treatment with metformin decreased phosphorylation of S6 protein. These experimental findings show that metformin is a potent inhibitor of cell proliferation in leiomyoma cells. This effect is mediated by AMPK activation and subsequent inhibition of the mTOR pathway. Thus, this study provides a possible mechanism of the action of metformin in the inhibition of leiomyoma cell growth.

Epigallocatechin-3-gallate potentiates curcumin's ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis.

BACKGROUND: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapeutic regimens. Two natural occurring compounds, curcumin and epigallocatechin gallate (EGCG), are reported to have anti-cancer activity. We previously reported that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway. However, challenges remain in overcoming curcumin's low bioavailability. METHODS: The human LMS cell line SKN was used. The effect of EGCG, curcumin or their combination on cell growth was detected by MTS assay. Their effect on AKT, mTOR, and S6 was detected by Western blotting. The induction of apoptosis was determined by Western blotting using cleaved-PARP specific antibody, caspase-3 activity and TUNEL assay. Intracellular curcumin level was determined by a spectrophotometric method. Antibody against EGCG cell surface receptor, 67-kDa laminin receptor (67LR), was used to investigate the role of the receptor in curcumin's increased potency by EGCG. RESULTS: In this study, we showed that the combination of EGCG and curcumin significantly reduced SKN cell proliferation more than either drug alone. The combination inhibited AKT, mTOR, and S6 phosphorylation, and induced apoptosis at a much lower curcumin concentration than previously reported. EGCG enhanced the incorporation of curcumin. 67LR antibody partially rescued cell proliferation suppression by the combination treatment, but was not involved in the EGCG-enhanced intracellular incorporation of curcumin. CONCLUSIONS: EGCG significantly lowered the concentration of curcumin required to inhibit the AKT-mTOR pathway, reduce cell proliferation and induce apoptosis in uterine LMS cells by enhancing intracellular incorporation of curcumin, but the process was independent of 67LR.