PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), v integrin is a crucial mediator of multicellular clustering and collective movement ; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent . Firstly, we found marked enrichment of v integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of v integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed v integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC . Overall, these results suggest that PEP06 polypeptide 30 inhibiting v integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

Research advances of M3 receptor: a new target for treating and preventing cardiovascular disease / 药学学报

Cardiovascular disease, with high morbidity and mortality, has been threatening the health of human beings. Therefore, expecting to find a more effective therapeutic method, a plenty of researchers devote themselves to the study of the cardiovascular disease all the time. Since discovered on the heart, M3 receptor of muscarinic acetylcholine receptor (mAchR, M receptor) became a new starting point of the research of the cardiovascular disease. With more and more investigation, many people found that M3 receptor could protect the heart from kinds of cardiovascular disease, which may make it a new hopeful therapeutic point. So, expecting to give support to the reference and encouragement for the study of disease related to M3 receptor in future, this review expounds M3 receptor on the heart from the main following aspects: the effect on the heart, the influence on the cardiovascular disease and the mechanism of M3 receptor involved.

Protective Effect of Wenxin Granula on Heart from Myocardial Infarction through Regulating Intracellular Ca2+ / 中草药·英文版

Objective To assess the anti-arrhythmic activity and cardioprotective effects of Wenxin Granula, a traditional Chinese formula (consisting of Salviae Miltiorrhizae Radix, Polygonati Rhizoma, Notoginseng Radix et Rhizoma, Nardostachyos Radix et Rhizoma, Angelicae Sinensis Radix, and Succinum), on heart in ischemic-induced myocardial infarction (MI) rats and compare with those of Amiodarone which have been demonstrated in clinic. Methods Rats were randomly divided into Sham-operated (control), Ml + Amiodarone [5 mg/(kg·d)] (MI), and MI + Wenxin Granula [10 mg/(kg·d)] groups and left anterior descending coronary artery was occluded in each group. After left anterior descending for 12 h, standard lead Ⅱ of administration electrocardiogram was recorded in order to analyze the occurrence of arrhythmia. After one month, the size of the infarct area of heart was evaluated by TTC staining method and haemodynamic function was assessed to detect the heart function. Laser scanning confocal microscope and the technique of patch clamp were used to detect the intracellular Ca2+ ([Ca2+]j) and L-type calcium current (ICa-L), respectively. Results Both Wenxin Granula [10 mg/(kg·d)] and Amiodarone [5 mg/(kg·d)] could markedly decrease the incidence of arrhythmia in heart of rats which were subjected to ischemic injury. After one month, Wenxin Granula could significantly decrease mortality to 22.22% and reduce the infarct area (P < 0.05), but Amiodarone did not. The mechanism may involve that Wenxin Granula attenuated [Ca2+]j decreasing in MI rats. Additionally, Wenxin Granula could obviously ameliorate the impaired heart function of MI rats by decreasing the elevated left ventricular end-diastolic pressure and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period. On the other hand, electrophysiological experiment results revealed that Wenxin Granula administration one month later also increased the reduced ICa-L density in rat ventricular myocytes in MI rats. The results of LSCM showed that Wenxin Granula could recover the amplitude of [Ca2+]j decreased by heart failure during long term. Conclusion Wenxin Granula could not only inhibit the incidence of arrhythmia but also decrease the mortality, which was accompanied by recovering the amplitude of [Ca2+]j. This protective effect of Wenxin Granula may partially be mediated through changing ICa-L.as well as increasing [Ca2+]j.

Bone marrow mesenchymal stem cells upregulate transient outward potassium currents in postnatal rat ventricular myocytes.

Bone marrow mesenchymal stem cell (BMSC) transplantation has been shown to effectively improve cardiac function in experimental animals and patients with myocardial infarction and heart hypertrophy. BMSCs exert potent effects on cardiomyocytes through the inhibition of cardiac apoptosis, the attenuation of cardiac inflammation, etc. However, novel biological actions of BMSCs on cardiomyocytes remain to be explored. The present study was designed to investigate whether BMSCs affect electrophysiological features of neonatal rat ventricular myocytes (NRVMs). BMSCs and NRVMs were indirectly co-cultured at a ratio of 1:10 with a semi-permeable membrane. We found that compared with mono-cultured NRVMs, co-cultured NRVMs exhibited an obvious increase of transient outward potassium current (I(to)), accompanied by significant changes in activation, inactivation and recovery of I(to). Meanwhile, K(V)4.2 mRNA which encodes the channel carrying I(to) was more abundant in co-cultured NRVMs than mono-cultured NRVMs. The increases in basic fibroblast growth factor (bFGF) and insulin growth factor-1 (IGF-1) levels were observed in culture medium of BMSCs. bFGF but not IGF-1 upregulated the K(V)4.2 mRNA expression and enhanced I(to) currents. Taken together, we conclude that BMSCs upregulate I(to) of NRVMs, at least partially, by secreting bFGF that in turn upregulates K(V)4.2 expression and alters the kinetics of I(to).

Inhibition of matrine on potassium currents in guinea pig ventricular myocytes / 中国药理学与毒理学杂志

AIM To elucidate the possible antiarrhythmic mechanism of matrine. METHODS Whole-cell patch-clamp technique was used to record ionic currents in ventricular myocytes. RESULTS In guinea pig ventricular myocytes, matrine 100 μmol·L-1 prolonged 90% action potential duration (APD90) by 40% at a stimulation of 0.1 Hz in a frequency-independent manner, inhibited IK1 by 47% at the test potential of -120 mV, reduced IKr,tail by 50% and had no effect on IKs,tail. CONCLUSION Matrine prolonged APD through blockade of multiple potassium currents, which may relate to its antiarrhythmic efficacy.

Biomechanical characteristics of reconstruction of femoral shaft fracture with medial cortical defect / 中国组织工程研究

BACKGROUND: After internal fixation is applied to femoral shaft fracture with medial cortical defect, the fixation device is often bended and broken due to the stress on it. So far, reliable methods have not been found to solve this problem in clinic.OBJECTIVE: To evaluate the biomechanical stability of the allograft bone plate after a bony defect of the medial cortex is reconstructed with allograft bone plate.DESIGN: A randomized controlled experimental study.SETTING: This trial was conducted in the Department of Orthopaedics, the 175 Hospital of Chinese PLA, and Laboratory of Biomechanics, First Military Medical University of Chinese PLA.PARTICIPANTS: This trial was conducted in Laboratory of Medical Biomechanics, First Military Medical University. MTS858 Biomix biomaterial testing machine was used to simulate model of femoral shaft fracture on 3male adult femurs donated voluntarily by their relatives, aged 23, 24 and 28years old.INTERVENTIONS: The fracture model of medial cortical defect was made in the femurs. Different kinds of fixation were applied and the results were compared between fixated femurs and the normal ones. The fixations included steel plate fixation(fixation for group 1 ), steel plate with allograft bone plate fixation(fixation for group 2), steel plate with allograft bone plate fixation and reduction of the medial cortical fragment(fixation for group 3).MAIN OUTCOME MEASURES: The vertical compression displacement under 500 N load, three-point bending strength under 10 N and anti-torsional angle under 300 N load are all measured.RESULTS: The vertical compression displacement and three-point bending strength of the control group were insignificantly different from those of the fixation group 3 ( P ＞ 0.05), but significantly different from those of the fixation group 1 and 2 ( P ＜ 0.05). The anti-torsional angle of the control group was significantly different from that of the three fixation groups( P ＜ 0. 05) . The result of fixation in fixation group 1 was the worst, better in fixation group 2and the best in fixation group 3.CONCLUSION: When there is a medial cortical defect in the femur, reconstruction with a bone plate can recover the integrity of the femoral medial cortex, and the successful rate of the plate internal fixation is increased.