Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1) to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose) polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma

Neuromuscular Electric Stimulation Enhances Endothelial Vascular Control and Hemodynamic Function in Paretic Upper Extremities of Patients with Stroke

Objective: To investigate the effects of neuromuscular electric stimulation (NMES) on endothelial vascular control and hemodynamic function in patients in rehabilitation after acute stroke. Design: Before- after trial. Setting: Inpatients in a tertiary hospital. Participants: Sixteen stroke patients (11 women, 5 men) with a mean age of 60.6 +/ - 19. 5 years. Interventions: All patients received NMES for paretic wrist extensor and flexor muscles 30 minutes daily, 5 days a week, for 4 weeks. The nonparetic upper extremities , which served as controls, did not receive NMES. Main Outcome Measures: Laser Doppler perfusion testing was conducted to measure cutaneous microcirculatory reponses to transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), as specific endothelium-dependent and - independent vasodilators, respectively. Arterial and venous hemodynamic function was also measured by impedance plethysmography. Results: Before NMES treatment, the venous capacity and compliance of the paretic extremities did not differ significantly from those of the nonparetic extremities. However, hyperemic arterial inflow, ACh-induced cutaneous perfusion, and the ratio of ACh- to SNP-induced cutaneous perfusion were lower in the paretic than in the nonparetic extremities. After NMES treatment, hyperemic arterial inflow and venous outflow increased by 21.5% and 57 .2%, respectively, in the paretic extremities (P<.05). ACh- induced cutaneous perfusion and the ratio of ACh- to SNP- induced cutaneous perfusion were also significantly enhanced in the paretic extremities. In contrast, hyperemic arterial inflow decreased by 39.6% in the nonparefic extremities (P< .05), and endothelium-dependent cutaneous vasodilation also decreased significantly. Conclusions: NMES therapy may enhance the hyperemic arterial response and endothelium- dependent dilation in skin vasculature in the paretic upper extremities of patients with stroke

Tai Chi Chuan Training Is Associated with Enhanced Endothelium-Dependent Dilation in Skin Vasculature of Healthy Older Men

OBJECTIVES: The vascular endothelium modulates vascular tone by synthesizing and metabolizing vasoactive substances. Endothelium-dependent vasodilation declines with age. This stud), investigated whether Tai Chi Chuan (TCC) training could enhance endothelial function in the skin vasculature of older men. SETTING: Community setting. DESIGN: Basic hemodynamic characteristics and skin vascular response to endothelium- dependent and -independent vasodilators were studied. PARTICIPANTS: Ten older men who practiced TCC 10 older healthy sedentary men, and 12 younger healthy sedentary men. The older TCC subjects had practiced classical Yang TCC for a mean standard deviation of 11.2 +/- 3.4 years; mean attendance was 5.1 +/- 1.8 times weekly. Sedentary subjects had not participated in any regular exercise training for at least 5 years. MEASUREMENTS: Different doses of 1% acetylcholine (ACh) and 1% sodium nitroprusside (SNP) were iontophoretically applied to the skin of subjects ' lower legs, and cutaneous microvascular perfusion responses were determined by laser doppler measurements. Additionally, arterial and venous hemodynamic variables were measured by impedance plethysmograph. RESULTS : The older TCC group had higher lower leg arterial blood flow ( LABF); LABF in response to reactive hyperemia, and lower leg venous capacity, tone and blood flow than their sedentary counterparts, but the older TCC group displayed similar arterial and venous hemodynamic variables to the younger sedentary group. The younger sedentary group had a higher ACh-induced Cutaneous perfusion and a higher ratio of ACh- to SNP -induced cutaneous perfusion than the two older groups. The older TCC group showed a higher ACh-induced Cutaneous perfusion and a higher ratio of ACh- to SNP- induced cutaneous perfusion than the older sedentary group . Skin vascular responses to SNP did not differ significantly between the three groups. CONCLUSIONS: Regular practice of TCC is associated with enhanced endothelium-dependent dilation in skin vasculature of older individuals. Moreover, TCC training may delay the age-related decline of venous compliance and hyperemic arterial response

Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men.

Exercise is linked with the type/intensity-dependent adaptive immune responses, whereas hypoxic stress facilitates the programmed death of CD4 lymphocytes. This study investigated how high intensity-interval (HIT) and moderate intensity-continuous (MCT) exercise training influence hypoxia-induced apoptosis and autophagy of CD4 lymphocytes in sedentary men. Thirty healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n=10) or MCT (sustained 60%VO2max, n=10) for 30 minutes/day, 5 days/week for 5 weeks, or to a control group that did not received exercise intervention (CTL, n=10). CD4 lymphocyte apoptotic and autophagic responses to hypoxic exercise (HE, 100 W under 12%O2 for 30 minutes) were determined before and after various regimens. The results demonstrated that HIT exhibited higher enhancements of pulmonary ventilation, cardiac output, and VO2 at ventilatory threshold and peak performance than MCT did. Before the intervention, HE significantly down-regulated autophagy by decreased beclin-1, Atg-1, LC3-II, Atg-12, and LAMP-2 expressions and acridine orange staining, and simultaneously enhanced apoptosis by increased phospho-Bcl-2 and active caspase-9/-3 levels and phosphotidylserine exposure in CD4 lymphocytes. However, five weeks of HIT and MCT, but not CTL, reduced the extents of declined autophagy and potentiated apoptosis in CD4 lymphocytes caused by HE. Furthermore, both HIT and MCT regimens manifestly lowered plasma myeloperoxidase and interleukin-4 levels and elevated the ratio of interleukin-4 to interferon-γ at rest and following HE. Therefore, we conclude that HIT is superior to MCT for enhancing aerobic fitness. Moreover, either HIT or MCT effectively depresses apoptosis and promotes autophagy in CD4 lymphocytes and is accompanied by increased interleukin-4/interferon-γ ratio and decreased peroxide production during HE

A randomized controlled trial of enhancing hypoxia-mediated right cardiac mechanics and reducing afterload after high intensity interval training in sedentary men

Abstract Hypoxic exposure increases right ventricular (RV) afterload by triggering pulmonary hypertension, with consequent effects on the structure and function of the RV. Improved myocardial contractility is a critical circulatory adaptation to exercise training. However, the types of exercise that enhance right cardiac mechanics during hypoxic stress have not yet been identified. This study investigated how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) influence right cardiac mechanics during hypoxic exercise A total of 54 young and healthy sedentary males were randomly selected to engage in either HIIT (3-min intervals at 40% and 80% of oxygen uptake reserve, n = 18) or MICT (sustained 60% of oxygen uptake reserve, n = 18) for 30 min/day and 5 days/week for 6 weeks or were included in a control group (CTL, n = 18) that did not engage in any exercise. The primary outcome was the change in right cardiac mechanics during semiupright bicycle exercise under hypoxic conditions (i.e., 50 watts under 12% FiO2 for 3 min) as measured by two-dimensional speckle tracking echocardiography.: After 6 weeks of training, HIIT was superior to MICT in improving maximal oxygen consumption (VO2max). Furthermore, the HIIT group showed reduced pulmonary vascular resistance (PVR, pre-HIIT:1.16 ± 0.05 WU; post-HIIT:1.05 ± 0.05 WU, p < 0.05) as well as an elevated right ventricular ejection fraction (RVEF, pre-HIIT: 59.5 ± 6.0%; post-HIIT: 69.1 ± 2.8%, p < 0.05) during hypoxic exercise, coupled with a significant enhancement of the right atrial (RA) reservoir and conduit functions. HIIT is superior to MICT in dilating RV chamber and reducing radial strain but ameliorating radial strain rate in either systole (post-HIIT: 2.78 ± 0.14 s-1; post-MICT: 2.27 ± 0.12 s-1, p < 0.05) or diastole (post-HIIT: − 2.63 ± 0.12 s-1; post-MICT: − 2.36 ± 0.18 s-1, p < 0.05). In the correlation analysis, the changes in RVEF were directly associated with improved RA reservoir (r = 0.60, p < 0.05) and conduit functions (r = 0.64, p < 0.01) but inversely associated with the change in RV radial strain (r = − 0.70, p < 0.01) and PVR (r = − 0.70, p < 0.01) caused by HIIT. HIIT is superior to MICT in improving right cardiac mechanics by simultaneously increasing RA reservoir and conduit functions and decreasing PVR during hypoxic exercise