Adipose-derived Mesenchymal Stem Cells Improve Both Spontaneous Pain and Allodynia in a Rat Neuropathic Pain Model

Purpose：Several studies investigated the efficacy of transplanting adipose-derived mesenchymal stem cells（ADMSCs）in the treatment of neuropathic pain in animals. However, these studies evaluated the effects of ADMSCs transplantation by assessing the mechanical allodynia but not spontaneous pain. Here, we verify whether ADMSCs transplantation improves spontaneous pain in a rat model of neuropathic pain. Methods：ADMSCs were isolated from rat adipose tissue and cultured. Chronic constriction injury（CCI） model rats were created by surgical maneuver. A total of 20 F344 rats underwent surgery and were divided into 2 groups, the ADMSCs group and the control group. One week after CCI surgery, ADMSCs were transplanted into the epineurium of the damaged nerve. The effects of ADMSCs transplantation were evaluated by the number of spontaneous pain-related behaviors and the degree of mechanical allodynia. The degree of mechanical allodynia was assessed with the von-Frey filament test. Results：No rats died during the experiments and all CCI model rats were established successfully. ADMSCs transplantation improved mechanical allodynia on and after 7-day post-transplantation and spontaneous pain on and after 21-day post-transplantation with the statistically significant differences. These improvement effects were observed until 6-week post-transplantation in mechanical allodynia and 5-week post-transplantation in spontaneous pain. Conclusion：ADMSCs transplantation improved not only mechanical allodynia but also spontaneous pain. ADMSCs transplantation may be an effective treatment for neuropathic pain in clinical practice

CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses

A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected CA9 and PRELID2 as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment

Earthquake-induced prompt gravity signals identified in dense array data in Japan

Abstract Earthquake ruptures cause mass redistribution, which is expected to induce transient gravity perturbations simultaneously at all distances from the source before the arrival of P-waves. A recent research paper reported the detection of such prompt gravity signals from the 2011 Tohoku-Oki earthquake by comparing observed acceleration waveforms and model simulations. The 11 observed waveforms presented in that paper recorded in East Asia shared a similar trend above the background seismic noise and were in good agreement with the simulations. However, the signal detection was less quantitative because the significance of the observed signals was not discussed and the waveforms at other stations in the region were not shown. In this study, similar trends were not observed in most of the data recorded near the stations used in the aforementioned study, suggesting that the reported signals were only local noises. We thus took a different approach to identify the prompt signals. We optimized the multi-channel data recorded by superconducting gravimeters, broadband seismometers, and tiltmeters. Though no signal was identified in the single-trace records, the stacked trace of the broadband seismometer array data in Japan showed a clear signal above the reduced noise level. The signal amplitude was 0.25 nm/s2 for an average distance of 987 km from the event hypocenter. This detection was confirmed with a statistical significance of $$7\sigma$$ 7σ , where $$\sigma$$ σ is the standard deviation of the amplitude of the background noise. This result provided the first constraint on the amplitude of the observed prompt signals and may serve as a reference in the detection of prompt signals in future earthquakes