Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness.

Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response (n=12), and healthy control subjects (n=6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics.

[Poteintation of vincristine-induced apoptosis by tetrandrine, neferine and dauricine in the human mammary MCF-7 multidrug-resistant cells].

AIM: To investigate the poteintation of vincristine-induecd apoptosis by tetrandrine, neferine and dauricine isolated from Chinese medicinal plants in the human mammary MCF-7 multidrug resistant cells. METHODS: The apoptotic cells were detected by fluorescent staining of a combination of Hoechst 33342 and propidium iodide (PI), flow cytometry and agarose electrophoresis. RESULTS: The apoptotic cells induced by vincristine alone accounted for about 10% of all the cancer cells, while the percentage of apoptotic cells induced by a combination of vincristine with tetrandrine, neferine, or dauricine was found to be significantly higher than that by vincristine alone, and their reversal effects were positively correlated with the drug concentration and the exposure time. In addition, tetrandrine was shown to be the most potent in the reversal efficacy among the three compounds to be tested for apoptosis in vitro. CONCLUSION: Tetrandrine, neferine and dauricine showed obvious potenitiation of vincristine-induced apoptosis in the human mammary MCF-7 multidrug-resistant cells.

Synergistic anticancer effects of tetrandrine combined with doxorubicin or vincristine in vitro.

AIM: To study the interaction between tetrandrine (Tet) and doxorubicin (Dox) or vincristine (Vin) against human breast cancer cell lines MCF-7 and MCF-7/Dox or human nasopharyngeal cancer cell lines KB and KBV200 in vitro. METHODS: Anticancer activities of a drug alone and a drug combination of Tet and Dox or Vin were determined by tetrazolium (MTT) method. The interaction between Tet and Dox or Vin was evaluated by both a value of a sum of fractional inhibitory concentration (SFIC) and an isobologram method. RESULTS: The SFIC values of the three-different-ratio combinations between Tet and Dox ranged from 0.14 to 0.38 for MCF-7, and 0.10 to 0.29 for MCF-7/Dox; those of Tet-Vin combinations ranged from 0.21 to 0.37 for KB, and 0.32 to 0.63 for KBV200. All the SFIC values of the combination between Tet and Dox or Vin were less than 1.0 when the 3 ratios of the 2 drugs in combination were used, and the shapes of isobolic curves obtained from the combination were concave. CONCLUSION: The interaction between Tet and Dox or Vin against the human cancer cells was markedly synergistic.

[Effects of scoparone on hemodynamics in anesthetized rabbits].

The effects of scoparone (Sco), tetramethylpyrazine (TMP), and papaverine (Pap) on hemodynamics were compared in anesthetized rabbits. Three dosage levels (1.25, 2.5, 5 mg.kg-1, iv) were used for each agent. Sco lowered the blood pressure (BP), increased the cerebral blood flow (CBF) dose-dependently, but did not show significant influence on the femoral artery blood flow (FBF), the maximal decrease of BP, and the maximal increases of CBF being 15% and 20% of the control, respectively. In contrast, TMP raised the BP as well as increased the CBF and FBF simultaneously. Pap, however, lowered the BP, slightly increased the CBF and decreased the FBF only at large doses. The results suggested that Sco may cause a selective dilatation of cerebral blood vessels.

[Effects of 6,7-dimethoxycoumarin on left ventricular function and hemodynamics in anesthetized cats].

Scoparone (6,7-dimethoxycoumarin 1.25, 2.5, 5 mg.kg-1) influenced the cardiohemodynamic functions in anesthetized cats. After i.v. injection the LVP-dP/dt loops and blood pressure were decreased. Both the contractile and relaxant functions of the left ventricle were inhibited. These were demonstrated by the reduction of dP/dtmax, Vmax, Vce-dp40, LVSP, prolongation of LVET, diminution of -dP/dtmax, and extension of the constant time of isometric diastolic pressure decay (T value). The preload of the left ventricle, LVEDF, was raised and the afterload (MAP, TPB) was decreased: The systolic volume, systolic index, cardiac output, and cardiac index were decreased slightly. The parameters TTI and TTI x HR, which reflect the myocardial oxygen consumption, were reduced. Furthermore, the heart rate was decreased at 5 mg.kg-1. The results indicate that scoparone could suppress the myocardial activity.