Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells.

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3ß was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.

Effect of Tongxinluo on pulmonary hypertension and pulmonary vascular remodeling in rats exposed to a low pressure hypoxic environment.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), which is a Chinese medicine rooted from traditional used herbs, has been used in clinic to treat cardiovascular and cerebrovascular diseases. However, it remains unknown whether TXL alleviates low pressure hypoxic pulmonary hypertension. AIM OF THE STUDY: Here, we aimed to observe the influence of TXL on pulmonary hypertension in a rat model that exposed to high altitude environment characterized by low pressure hypoxia. MATERIALS AND METHODS: A total of 32 male Sprague-Dawley rats were divided into four groups: control group (normal pressure and normoxia), pulmonary hypertension group (PAH, the parameter is equal to that in altitude 5000m), TXL group (rats living in environment equal to that at altitude of 5000m received TXL treatment), vardenafil group (VDNF, rats living in environment equal to that altitude of 5000m received vardenafil treatment). The high altitude environment was created in chamber by adjusting the inner pressure and oxygen content concomitantly. Before entering the chamber, the TXL group was given TXL (1.2gkg-1d-1) for 28 days, and the VDNF group was given VDNF (0.1gkg-1d-1) for 28 days. After 28 days, the mean pulmonary artery pressure (mPAP) and right ventricular pressure was measured using right heart catheterization. The weight of the right ventricle (RV), left ventricle (LV) and interventricular septum (IVS) was measured, and the right ventricular mass index was calculated. Lung tissue was subjected to hematoxylin and elastic fiber staining, and the medial wall thickness (MT), medial wall cross-sectional area (MA), MT%, and MA% were measured. Proliferative activity within the pulmonary arteries was quantified by Ki67staining. RESULTS: After 28 days, as compared with that in normal control group, animals living in the chamber (PAH group) showed a significant increase in mPAP( 47.5mmHg versus 18mmHg), RV/LV+IVS (0.45 versus 0.21) and MA% (78% versus 44%), respectively. Administration of TXL resulted in a significant decrease of 20mmHg in mPAP, returning of RV/LV+IVS to 0.27, and a 40% reduction in MT% compared with that in PAH group. In the VDNF group, RV/LV+IVS and MT% was 0.268 and 38.77, significantly lower than that in PAH group. While, mPAP increased by 12.5mmHg with treatment by VDNF. In contrast to the PAH group, alpha- Smooth Muscle Actin (α-SMA reduced by 19% in the TXL group (p=0.005) and 16% in the VDNF group (p=0.01). Ki67 expression in the VDNF group was significantly lower than the PAH group (P<0.01). Ki67 expression in the TXL group was significantly lower than the PAH group (P<0.01). Compared with the VDNF group, the indexes above reduced in the TXL group. Our results indicate that TXL significantly reduces pulmonary artery pressure, right ventricular hypertrophy, pulmonary small artery wall thickness, and luminal stenosis. In addition, smooth muscle proliferation markedly decreased and muscular artery decreased. However, TXL was unable to restore parameters to control levels. CONCLUSIONS: The automatic-adjusted low pressure hypoxic chamber was capable of establishing a pulmonary hypertension rat model at an altitude of 5000m. Compared with VDNF, TXL decreased mPAP and right ventricular hypertrophy index (RVHI) in the pulmonary hypertension rat model, and prevented vascular remodeling by reducing small pulmonary artery thickening, smooth muscle thickening and proliferation. Thus, TXL may be a potential treatment for pulmonary hypertension.

[Effects of maternal exposure to nano-alumina during pregnancy on neurodevelopment in offspring mice].

OBJECTIVE: To observe the effects of maternal exposure to nano-alumina during pregnancy on the neurodevelopment in offspring mice. METHODS: Female ICR mice began to be exposed to nano-alumina 10 d before mating, and the nano-alumina exposure lasted till offspring mice were born. All the female mice were randomly divided into 5 groups: solvent control group (saline), nano-carbon group (11.76 mg/ml), micro-alumina group (50 mg/ml), 50 nm alumina group (50 mg/ml), and 13 nm alumina group (50 mg/ml). All the mice were treated by nasal drip (10 µl/time) 3 times daily till offspring mice were born. Physiological indices, reflex and sensory function test, endurance test, Morris water maze test, positioning and navigation test, and open field test were used to evaluate the neurodevelopment of newborn mice. RESULTS: On day 28, the body weight of 13 nm alumina group (16.73±4.04 g) was significantly lower than that of solvent control group (20.45±2.50 g) (P<0.01); the 13 nm alumina group had significantly delayed time to ear opening compared with the solvent control group (4.91±0.78 d vs 4.45±0.50 d, P<0.01); compared with the solvent control group, the nano-carbon group, micro-alumina group, 50 nm alumina group, and 13 nm alumina group had significantly delayed time to eruption of teeth (10.05±0.23 d vs 10.32±0.48 d, 10.75±0.45 d, 10.32±0.47 d, and 10.79±0.49 d, P<0.05 or P<0.01). On days 4 and 7 after birth, compared with the solvent control group, other groups had significantly decreased proportions of mice which passed the cliff avoidance test (P < 0.05 or P < 0.01). On days 12 and 14 after birth, compared with the solvent control group, the nano-carbon group, 50 nm alumina group, and 13 nm alumina group had significantly reduced pre-suspension time in the endurance test (P < 0.05 or P < 0.01). The Morris water maze and positioning and navigation tests showed that the 13 nm alumina group had a significantly increased 5 d incubation period compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of platform crossings (P < 0.05 or P < 0.01). The open field test showed that the nano-carbon group and 13 nm alumina group had reduced numbers of rearings compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of modifications (P < 0.01). CONCLUSION: Maternal exposure to nano-alumina (13 nm) during pregnancy has inhibitory effects on the physical development and early behavioral development in newborn mice and can also inhibit the learning and memory abilities and adaptability to new environment in offspring mice. The neurodevelopmental toxicity of nano-alumina to newborn mice increases as the particle sizes of nano-alumina decrease, which has been demonstrated by the endurance test and number of rearings.

[Clinical observation on treatment of 43 women with polycystic ovary syndrome based on syndrome differentiation].

OBJECTIVE: To investigate the therapeutic effect of treatment based on syndrome differentiation and its influence on the serum levels of testosterone and insulin in women with polycystic ovary syndrome (PCOS). METHODS: Forty-three women, diagnosed with PCOS as well as syndrome of kidney yin deficiency or syndrome of spleen qi deficiency, were enrolled in the study. Twenty-five PCOS women with syndrome of kidney yin deficiency were treated with traditional Chinese herbs for nourishing yin to reduce fire (nourishing yin group), and 18 PCOS women with syndrome of spleen qi deficiency were treated with herbs for invigorating spleen and replenishing qi (replenishing qi group). Body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and the serum levels of insulin and testosterone before and after treatment were detected. RESULTS: Among the 43 cases, 20 cases had high serum testosterone level, in which 13 cases with syndrome of kidney yin deficiency, 7 cases with syndrome of spleen qi deficiency, but the difference had no statistic significance; 17 cases had high serum insulin level, in which 11 cases with syndrome of spleen qi deficiency, 6 cases with syndrome of kidney yin deficiency, the difference had statistic significance (P<0.05). In nourishing yin group, the serum levels of insulin and testosterone declined after treatment (P<0.05), and BMI, WHR and WC showed no significant changes. In replenishing qi group, the serum level of insulin declined after treatment (P<0.01), and BMI, WHR, WC and the serum level of testosterone showed no significant changes. CONCLUSION: Traditional Chinese herbs for nourishing yin to reduce fire can significantly reduce the serum levels of testosterone and insulin in PCOS women with syndrome of kidney yin deficiency, and herbs for invigorating spleen and replenishing qi can significantly reduce the serum level of insulin in PCOS women with syndrome of spleen qi deficiency.