Jiadifenolide induces the expression of cellular communication network factor (CCN) genes, and CCN2 exhibits neurotrophic activity in neuronal precursor cells derived from human induced pluripotent stem cells

Jiadifenolide has been reported to have neurotrophin-like activity in primary rat cortical neurons, and also possesses neurotrophic effects in neuronal precursor cells derived from human induced pluripotent stem cells (hiPSCs), as we have previously reported. However, the molecular mechanisms by which jiadifenolide exerts its neurotrophic effects in rat and human neurons are unknown. Thus, we aimed to investigate the molecular mechanisms and pathways by which jiadifenolide promotes neurotrophic effects. Here, we found that jiadifenolide activated cellular communication network factor (CCN) signaling pathways by up-regulating mRNA level expression of CCN genes in human neuronal cells. We also found that CCN2 (also known as connective tissue growth factor, CTGF) protein promotes neurotrophic effects through activation of the p44/42 mitogen-activated protein kinase signaling pathway. This is the first discovery which links neurotrophic activity with CCN signaling

Anomalous Radioisotope Production for 68ZnO Using Polyethylene by Accelerator Neutrons

We measured the yields of radionuclides after neutron irradiation on an enriched 68ZnO sample covered with polyethylene blocks. The neutrons were generated from the 9Be(d,n) reaction by 40 and 50 MeV deuterons. For 50 MeV deuterons we found anomalously large yields of 67Ga, 66Ga, 69mZn, and 64Cu, more than 20-times larger than the yields for a 68ZnO sample without the polyethylene blocks. At the same time, the yields of the same radioisotopes from an enriched metallic 68Zn sample were almost insensitive to the presence of polyethylene. On the other hand, for 40 MeV deuterons the enhanced production was not observed. This finding would provide a unique capability of accelerator neutrons to simultaneously produce large amounts of several radioisotopes via the neutrons- as well as protons-induced reactions on a single sample. The experimental data were compared with the yields calculated by the simulation code Particle and Heavy Ion Transport code System (PHITS). The calculated yields of these radioisotopes produced from the 68ZnO sample covered with the polyethylene blocks considerably disagree with the measured ones, while for the 68ZnO sample without the blocks they agree with each other

Efficacy and Safety of Naldemedine for Patients with Cancer with Opioid-Induced Constipation in Clinical Practice: A Real-World Retrospective Study

The efficacy and safety of naldemedine for opioid-induced constipation in patients with cancer has not been investigated in clinical practice. We conducted a multicenter, retrospective study to assess the effects of naldemedine among 10 Japanese institutions between June 2017 and August 2019. We evaluated the number of defecations 7 days before and after naldemedine administration. A total of 149 patients (89 male) with a median age of 72 years (range, 38–96) were included. The performance status was 0–1, 2, and ≥3 in 40, 38, and 71 patients, respectively. The median opioid dose in oral morphine equivalents was 30 mg/day (range: 7.5–800 mg). We observed 98 responders and 51 non-responders. The median number of defecations increased significantly in the 7 days following naldemedine administration from three to six (p < 0.0001). Multivariate analysis revealed that an opioid dose <30 mg/day [odds ratio, 2.08; 95% confidence interval, 1.01–4.32; p = 0.042] was significantly correlated with the effect of naldemedine. Diarrhea was the most common adverse event (38.2%) among all grades. The efficacy and safety of naldemedine in clinical practice are comparable to those of prospective studies, suggesting that it is effective in most patients