Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo.

Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5-2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg(fli-1a: EGFP)y1. Timo AIII (0.5-4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment.

[Effect of Curcumol on the Biological Behavior of Multiple Myeloma Cells].

Objective To observe the effect of curcumol on the biological behavior of multiple myeloma (MM) cells, thus studying its possible mechanisms for MM treatment. Methods Bone marrow mesenchymal stem cells (BMSCs) and multiple myeloma cell line 8226 (RPMI 8226) were taken as sub- jects, which were then divided into the RMPI 8226 group (cultured by RMPI 8226 alone) and the BMSCs + RMPI 8226 group (cultured by BMSCs and RMPI 8226). Curcumol in different concentrations (0. 1, 0.5, 1. 0 , 10.0 µg/mL) was added to cells in the two groups respectively. Cell proliferation, cell cycle, and ap' optosis induced by curcumol were examined by flow cytometry. The expressions of receptor activator of nuclear factor Kb ligand ( RANKL ) and osteoprotegerin ( OPG) were detected using reverse tran- scriptase-polymerase chain reaction (RT-PCR). Results Curcumol induced arrested cell cycle of RMPI 8226. The arrest of RMPI 8226 cell cycle was more obviously in the RMPI 8226 group than in the BMSCs + RMPI 8226 group. After curcumol treatment the cell proliferation of RPMI 8226 was significantly inhibited (P <0. 01) and its apoptosis was increased (P <0. 01). Co-cultured with BMSCs decreased curcumol in- duced apoptosis of RPMI 8226. Curcumol down-regulated the expression of osteogenic differentiation related gene RANKL, and up-regulated the expression of OPG. Conclusions Curcumol disturbed the cell cycle and induced apoptosis of RPMI 8226 cells. Curcumol up-regulated the expression of OPG as well as down-regulated the expression of RANKL. Co-culture with BMSCs could obviously inhibit curcumol in- duced apoptosis of MM cells, which might be associated with drug resistance of MM cells.

[Clinical research on post-stroke dysphagia treated with nape acupuncture and rehabilitation training].

OBJECTIVE: To observe the improvement in post-stroke dysphagia after treatment of nape acupuncture and rehabilitation training. METHODS: Eighty patients who were in compliance with the inclusive criteria were randomized into a conventional treatment group and a nape acupuncture group, 40 cases in each one, according to the admission sequence. In the conventional treatment group, on the basis of general medication, the rehabilitation training of swallowing function was applied. In the nape acupuncture group, on the basic treatment as the conventional treatment group, nape acupuncture group was given. RESULTS: After treatment, the improvements in bedside water swallowing test, SSA, VFSS and pharynx transit time were all superior to those before treatment for the patients in the two groups (all P < 0.05). The improvements in bedside water swallowing test, SSA, VFSS and pharynx transit time in the nape acupuncture group were all superior to those in the conventional treatment group (all P < 0.05). The total effective rate was 85.0% (34/40) in the nape acupuncture group, which was higher than 65.0% (26/40) in the conventional treatment group, indicating the significantly statistical difference between the two groups (P < 0.05). CONCLUSION: Nape acupuncture combined with rehabilitation training significantly improves swallowing function of the patients after stroke.

[Study on the scores of blood stasis syndrome of acute ischemic stroke and its correlation with TOAST subtypes].

UNLABELLED: OBJECTIVE To compare the differences in the scores of blood stasis syndrome (BSS) in three subtypes of acute ischemic stroke (AIS) based on modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, and to explore the influencing factors of BSS. METHODS: Patients with AIS were classified by modified TOAST criteria. The BSS score was determined in 418 patients of atherosclerosis thrombosis (AT), cardioembolism (CE), and small artery disease (SAD) subtypes. The BSS scores were compared in the three subtypes. Univariate analysis and multivariable Logistic analysis were carried out to analyze the influencing factors of BSS. RESULTS: As for the BSS score, CE (120.08 +/- 14.91) > AT (79.56 +/- 11.43) > SAD (37.88 +/- 8.32), and there was statistical difference among different subtypes (P < 0.01). Univariate analysis indicated that age, heart disease, carotid stenosis, NIHSS, GCS, and multiple infarction positions had significant effects on BSS. Multiple Logistic regression analysis suggested that age (OR: 1.71, 95% CII: 1.13-2.74, P = 0.034), heart disease (OR: 2.05,95% CI: 1.52-4.15, P = 0.000), carotid stenosis (OR: 2.74, 95% CI: 1.65-4.55, P = 0.007), and multiple infarction positions (OR: 3.46, 95% CI: 2.16-6.62, P = 0.005) were independent influencing factors of BSS. CONCLUSIONS: Different TOAST subtypes of BSS had different BSS scores, which was helpful to indicate the reasons for BSS. Age, heart disease, carotid stenosis, and multiple infarction positions were independent influencing factors of BSS.

[Chemical study on aerial parts of Ligusticum chuanxiong].

OBJECTIVE: To study the chemical constituents of the aerial parts of Liusticum chuanxiong. METHOD: The chemical components were isolated by silica gel and Sephadex LH-20 column chromatography. Structures were elucidated on the basis of physico-chemical properities and spectral data. RESULT: Eight chemical constituents were isolated, and identified as protocatechuic acid (1), caffeic acid (2), scopoletin (3), apigenin (4), quercetin (5), cosmosiin (6), kaempferol-3-O-beta-D-glucopyranosid (7) and glucose (8). CONCLUSION: Compounds 1-8 were obtained from the aerial parts of the plant for the first time, compounds 3-8 were obtained from the plant for the first time.