Adenosine triphosphate (ATP) is an extracellular signaling molecule that mainly affects the pathophysiological situation in the body and can be sensed by purinergic receptors, including ionotropic P2X7. Neuronal stem cells (NSCs) remain in adult neuronal tissues and can contribute to physiological processes via activation by evoked pathophysiological situations. In this study, we revealed that human-induced pluripotent stem cell-derived NSCs (iNSCs) have ATP-sensing ability primarily via the purinergic and ionotropic receptor P2X7. Next, to develop a machine learning (ML)-based screening system for food-derived neuronal effective substances and their effective doses, we collected ATP-triggered calcium responses of iNSCs pretreated with several substances and doses. Finally, we discovered that ML was performed using composite images, each containing nine waveform images, to achieve a better ML model (MLM) with higher precision. Our MLM can correctly sort subtle unidentified changes in waveforms produced by pretreated iNSCs with each substance and/or dose into the positive group, with common mRNA expression changes belonging to the gene ontology signatures.

The effects of Ryanodine, an inhibitor of salcoplasmic reticulum function, was investigated in isolated hearts of the Wistar rat strain. The cytosolic calcium was measured with the intracellular Ca2+ fluorescent indicator Fura-2. After 3 minutes perfusion of various cardioplegic solution which were added potassium (the concentration; 20 mmol/L) and four Ryanodine groups (1, 4, 10, and 20 nmol/L), these were obtained cardiac arrest. The arrested hearts were kept at 37 degrees C (normothermia) measuring hemodynamic studies. Hemodynamic parameters were heart rate, LVDP, LV dp/dt, coronary flow, and the intracellular calcium fluorescents which were calculated intracellular Ca2+. The significant difference was not noted in LVDP, but comparable improvement was achieved with Ryanodine groups (p < 0.05; 20 nM vs 0 nM). Other cardiac functions were likely same as above. The cytosolic calcium concentration of Ryanodine groups was depressed during cardiac arrest, it was 97.4 +/- 17.2% at the end of cardiac arrest, and it was slowly increased to 161.9 +/- 46.9% after 40 minutes reperfusion. On the other hand, that of the control group was higher than Ryanodine groups at every measuring points about two times. There was significant difference between both groups (p < 0.01). Concequently these phenomena caused that Ca2+ handling in the salcoplasmic reticulum were supressed by Ryanodine and the contractile function was recovered for that reason.