Magnolol regulates miR-200c-3p to inhibit epithelial-mesenchymal transition and retinoblastoma progression by modulating the ZEB1/E-cadherin axis in vitro and in vivo.

BACKGROUND: Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. PURPOSE: The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, ß-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. RESULTS: Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/ß-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. CONCLUSION: Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

The oculocardiac reflex during strabismus surgery: its relationship to preoperative clinical eye findings and subsequent postoperative emesis.

PURPOSE: To compare the occurrence of significant bradycardia due to the oculocardiac reflex (OCR) during strabismus surgery and its relationship to preoperative clinical eye findings and subsequent development of postoperative emesis. METHODS: The medical records of consecutive patients who underwent strabismus surgery August 2006 to June 2009 were retrospectively reviewed. OCR was defined as presence of dysrhythmia or a sudden heart rate decrease ≥ 20% after traction on the extraocular muscle. OCR incidence was compared between the first, second, and third (if any) extraocular muscles in patients who had multiple-muscle strabismus surgery and also between specific muscles (eg, medial rectus vs lateral rectus muscle). Associations with OCR were compared for different strabismus types. Vomiting was considered postoperative if it occurred before discharge of the patient at noon on the day following surgery. Risk factors for OCR and postoperative vomiting were evaluated by logistic regression analysis. RESULTS: A total of 111 records were reviewed; 41 patients (37%) experienced OCR. Incidence of OCR and absence of OCR during traction of the first muscle were significantly associated with events during traction of the second (χ(2) = 36.681, P < 0.001) and third muscles (Fisher exact test, P = 0.030). The best predictors of OCR were the absence of fine stereopsis and a larger number of surgically treated muscles. Of the 111 patients, 30 (27%) who had postoperative vomiting, the best predictors were female sex and young age. CONCLUSIONS: In our cohort, patients experiencing intraoperative OCR when the first extraocular muscle was manipulated during multiple-muscle strabismus surgery were likely to experience it again during traction of additional muscles. More severe postoperative vomiting was common in these patients. OCR was associated with the preoperative absence of fine stereopsis.

Exercise behaviors in breast cancer survivors in Taiwan.

BACKGROUND: Although exercise is a recommended rehabilitation intervention for many breast cancer survivors, exercise activity after cancer treatment is rarely reported in this patient group in Taiwan. OBJECTIVE: The objectives of this study were to analyze trends in exercise activity in breast cancer survivors in Taiwan. INTERVENTIONS/METHODS: This prospective, longitudinal study with repeated-measures design used standardized instruments to measure trends in exercise activity but performed no treatments or interventions. RESULTS: Of the 196 breast cancer survivors who participated in this study, 39% regularly engaged in light-to-moderate intensity exercise for approximately 15 minutes per day throughout the 6-month period of the study. Of these, 40% indicated that their exercise stage had increased, and only 13% indicated that their exercise stage had decreased. The most common exercise activities were walking, hiking, calisthenics, folk dancing, chi kung and tai chi. Although most women reported that exercise made them feel better both physically and emotionally, most said that they exercised mainly for health maintenance reasons. CONCLUSIONS: Frequency, duration, and intensity of exercise significantly increased during the 6-month study but did not reach the recommended levels. Most women believed that physical activity enhanced their recovery from cancer treatment. IMPLICATIONS FOR PRACTICE: When planning patient education interventions for breast cancer survivors, healthcare professionals should consider not only the role of exercise in breast cancer recovery, but also trends in exercise behavior among breast cancer survivors. The findings of this study contribute to the literature on exercise trends in breast cancer survivors.