Research progress of Notch signaling pathway in tumor / 基础医学与临床

Notch gene encodes a class of highly conserved cell surface receptors that determine the fate of cells in embryonic development and mature tissue, which is an important pathway of communication between adjacent cells, and then regulates of cell development, proliferation and apoptosis. The occurrence and progression of multiple tumors are associated with abnormal Notch signaling pathways. For different tumors, it is important significance for anti-tumor therapy to effectively regulate the Notch participants and target molecules.

Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function / 中华医学杂志(英文版)

<p><b>Background</b>Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection.</p><p><b>Methods</b>After intragastric administration of TXL (0.1 ml/10 g body weight) to C57BL/6J wild-type mice (n = 8) and ApoE-/- mice (n = 8), total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate (HR), left ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and left ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity (PSV), end diastolic flow velocity, and mean flow velocity (MFV) were measured. The pulsatility index (PI) and resistant index were calculated in order to evaluate the vascular elasticity and resistance. The endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor (VEGF). Immunohistochemical detection was performed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P < 0.05 was considered statistically significant.</p><p><b>Results</b>Although there was no significant decrease of cholesterol level (F = 2.300, P = 0.240), TXL inhibited the level of triglyceride and VLDL (F = 9.209, P = 0.024 and F = 9.786, P = 0.020, respectively) in ApoE-/- mice. TXL improved heart function of ApoE-/- mice owing to the elevations of LVEF, SV, CO, and LVFS (all P < 0.05). TXL enhanced aortic PSV and MFV (F = 10.774, P = 0.024 and F = 11.354, P = 0.020, respectively) and reduced PI of ApoE-/- mice (1.41 ± 0.17 vs. 1.60 ± 0.17; P = 0.037). After incubation with 10 μmol/L acetylcholine, the ApoE-/- mice treated with TXL aortic segment relaxed by 44% ± 3%, significantly higher than control group mice (F = 9.280, P = 0.040). TXL also restrain the angiogenesis of ApoE-/- mice aorta (F = 21.223, P = 0.010). Compared with C57BL/6J mice, the MVD was decreased in heart tissue of untreated ApoE-/- mice (54.0 ± 3.0/mmvs. 75.0 ± 2.0/mm; F = 16.054, P = 0.010). However, TXL could significantly enhance MVD (65.0 ± 5.0/mmvs. 54.0 ± 3.0/mm; F = 11.929, P = 0.020) in treated ApoE-/- mice. In addition, TXL obviously increased the expression of VEGF protein determined by Western blot (F = 20.247, P = 0.004).</p><p><b>Conclusions</b>TXL obviously improves the ApoE-/- mouse heart function from different pathways, including reduces blood fat to lessen atherosclerosis; enhances aortic impulsivity, blood supply capacity, and vessel elasticity; improves endothelium-dependent vasodilatation; restraines angiogenesis of aorta-contained plaque; and enhances MVD of heart. The molecular mechanism of MVD enhancement maybe relate with increased VEGF expression.</p>

Changes in common chemical signal molecules of neuroendocrine-immune network and intervention of Tongxinluo in rats under hypoxia qi-asthenia condition / 第二军医大学学报

Objective: To investigate the changes in common chemical signal molecules of neuroendocrine-immune (NEI) network and intervention of Tongxinluo (TXL, ultramicro-pulverization) of rats under hypoxia qi-asthenia condition. Methods: Forty-five male Wistar rats were randomly assigned to the following groups: control group, qi-asthenia model group and TXL group (n=15). The rats in the former 2 groups were gavaged with CMC-Na (10 ml/ kg) once daily; those in the TXL group were gavaged with TXL (ultramicrot-pulverization) suspended in CMC-Na (10 ml/kg) once daily; After gavage, animals in the qi-asthenia model group and TXL group were placed in a cabin with normal pressure hypoxia (7 h daily, 6 d weekly for 5 weeks). At the end of the experiment, the biological characters of rats were observed and arterial blood gas was analyzed. The serum contents of serotonin (5-HT), norepinephrine (NE), epinephrine (E), dopamine (DA) and IFN-γ and TRH level in the hypothalamus were examined by enzyme linked immunosorbent assay (ELISA); the serum contents of corticosterone (Cort), T3,T4,IL-1β,TNF-α, and corticotropin release hormone(CRH) in the hypothalamus, and adrenocorticotropic hormone/thyroid stimulating hormone(ACTH/TSH) in the hypophysis cerebri were examined using radio-immunity method. Results: Compared with control group, the biological character scores of rats in the qi-asthenia model group were significantly bigher(P

Comfortable lifestyle-induced imbalance of neuro-endocrine-immunity network: a possible mechanism of vascular endothelial dysfunction / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the changes of vascular endothelial functions and general neuro-endocrine-immunity (NEI) network under the state of qi-deficiency syndrome induced by excessive idleness and to approach their internal relevance and illuminate initially the pathophysiological mechanism of vascular lesion induced by excessive idleness.</p><p><b>METHODS</b>A total of 100 male Wistar rats were randomly divided into the control group and the qi-deficiency syndrome model group, 50 rats in each group. The qi-deficiency syndrome model was established by feeding the animals with hyper-alimentation diet in combination with restricting movement for 10 weeks. Changes of common chemical signal molecules related to NEI and vascular endothelial functions were measured by the end of the experiment. Furthermore, their internal relevance was analyzed by the method of canonical correlation analysis.</p><p><b>RESULTS</b>The vascular endothelial structure and function were obviously injured in the model group. Compared with the control group, the chemical signal molecules, such as 5-hydroxytryptamine (5-HT), corticosterone (CORT), triiodothyronine (T3), tetraiodothyronine (T4), angiotensin II (Ang II), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood of the model group (n=43) were changed significantly (P<0.05 or P<0.01). Canonical correlation analysis showed that vascular endothelial dysfunction was correlated to the changes of these signal molecules in the NEI network.</p><p><b>CONCLUSIONS</b>Comfort-based lifestyle induced not only vascular endothelial dysfunction but also an imbalance of the NEI network. Vascular endothelial dysfunction and the imbalanced NEI network interacted with each other, and an imbalance of the NEI network may be the pathophysiologic basis for the genesis and development of vascular endothelial dysfunction, even diseases of the blood vessel.</p>

The effects of Tongxinluo Supermicro Powder on nuclear factor-kappaB, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in aorta of rabbits fed with high-lipid diet / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of Tongxinluo Supermicro Powder on the nuclear factor-kappaB (NF-kappaB), inter-cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in aorta of rabbits fed with high-lipid diet.</p><p><b>METHODS</b>Healthy male New Zealand rabbits were randomly divided into 4 groups (n = 8 each): control group, model group, atorvastatin group (3 mg x kg(-1) x d(-1) per gavage), and Tongxinluo group (0.31 g x kg(-1) x d(-1) per gavage). At the end of 6 weeks, the expression of NF-kappaB, ICAM-1 and VCAM-1 were observed by immunochemistry methods, Western blotting and reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULT</b>The nuclear translocation of NF-kappaB in aortic endothelial cells and the gene expressions of NF-kappaB, ICAM-1 and VCAM-1 at protein and mRNA levels of the model group was significantly increased compared that in the control group (all P < 0.05), these effects could be significantly attenuated by atorvastatin and Tongxinluo Supermicro Powder (P < 0.01 vs. model group).</p><p><b>CONCLUSIONS</b>Similar as atorvastatin, Tongxinluo Supermicro Powder could relieve the process of atherosclerosis by decreasing the nuclear translocation of NF-kappaB and reducing the expression of ICAM-1, VCAM-1 in this model.</p>

Experimental study on effect of Tongxinluo on nerve cell apoptosis after cerebral ischemia in middle cerebral arterial obstructive model rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the action mechanism of Tongxinluo Capsule (TXL) in protecting brain from ischemic damage.</p><p><b>METHODS</b>SD rats were divided into five groups randomly, the sham operation group, the model group, the MK-801 group, the large and low dosage TXL groups (TXLL and TXLS). After the middle cerebral arterial obstructive (MCAO) model was established, peritoneal injection of MK-801 0.5 mg/kg per day was given to the MK-801 group, and 1.0 g/(kg x d) and 0.5 g/(kg x d) of TXL powder was administered in twice via gastrogavage to the two TXL groups respectively. The nerve cell apoptosis rate, protein and mRNA expressions of Caspase-3, p53 and heat shock protein (HSP70) were observed using flow cytometry, Western blot and RT-PCR technique.</p><p><b>RESULTS</b>Both TXL and MK-801 could obviously lower the apoptosis rate in model rat (P < 0.05, P < 0.01), TXLL showed the optimal effect. Caspase-3, p53 protein and mRNA expression in the model group were obviously higher than those in the sham operated group. As compared with the model group, the expressions of Caspase-3 and p53 were lower and those of HSP70 and mRNA were higher in the two TXL and MK-801 groups (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>TXL displays it brain protective effect through reducing nerve cell apoptosis rate in MCAO model rats, the mechanism may be related to its actions in inhibiting apoptosis related factors Caspase-3 and p53, and promoting stress protecting factor HSP70.</p>