Definitive treatment of stroke constitutes an important thesis of regenerative medicine in the cerebrovascular field. However, to date, no cell therapy products for stroke are yet on the market. In this study, we examined the clinical research trends related to cell therapy products in the stroke field based on data obtained from the ClinicalTrials.gov website and International Clinical Trials Research Platform (ICTRP) portal site. These data do not offer results of clinical trials comprehensively but provide information regarding various attributes of planned clinical trials including work in progress. We selected 78 cell therapy studies related to the field of stroke treatment from ClinicalTrial.gov and ICTRP. These were analyzed according to, e.g., the reporting countries, origin (autologous or allogeneic), of cell used, cell types and source organs, the progress of translational phases, target phase of the disease (acute or chronic stroke), and route of administration. This analysis revealed a trend whereby in the acute phase, mesenchymal stem cells were administered intravenously at a relatively higher dose, whereas in the chronic phase a small number of cells were administered intracranially. Only two randomized controlled Phase III studies with over 100 patients are registered, but none of them has been completed. Thus, cell therapy against stroke appears to constitute a premature area compared with cartilage repair as assessed in our previous report. In addition, tracking by means of the ID number of each trial via PubMed revealed that 44% of clinical studies in this field have corresponding published results, which was also discussed.

LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5. siRNA knockdown experiments indicate that TRBP is important for Cardiovirus-triggered interferon responses, but TRBP is not involved in Sendai virus-triggered interferon response that is mediated mainly by RIG-I. To support functional interaction with LGP2, overexpressed TRBP increased Cardiovirus-triggered interferon promoter activity only when LGP2 and MDA5 are co-expressed but not MDA5 alone. Together, our findings illustrate a possible connection between an RNAi-regulatory factor and antiviral RNA recognition that is specifically required for a branch of the virus induced innate immune response.

The induced pluripotent stem cell (iPSC) was first described more than 10 years ago and is currently used in various basic science and clinical research fields. The aim of this report is to examine the trends in research using iPSCs over the last 10 years. The 2006-2016 PubMed database was searched using the MeSH term "induced pluripotent stem cells." Only original research articles were selected, with a total of 3323 articles. These were classified according to research theme into reprogramming, differentiation protocols for specific cells and/or tissues, pathophysiological research on diseases, and discovery of new drugs, and then the trends over the years were analyzed. We also focused on 232 research publications on the pathophysiological causes of diseases and drug discovery with impact factor (IF; Thomson Reuters) of six or more. The IF of each article was summed up by year, by main target disease, and by country, and the total IF score was expressed as trends of research. The trends of research activities of reprogramming and differentiation on specific cells and/or tissues reached maxima in 2013/2014. On the other hand, research on pathophysiology and drug discovery increased continuously. The 232 articles with IF ≥6 dealt with neurological, immunological/hematological, cardiovascular, and digestive tract diseases, in that order. The majority of articles were published from the United States, followed by Japan, Germany, and United Kingdom. In conclusion, iPSCs have become a general tool for pathophysiological research on disease and drug discovery.

Conversion of CD4+CD25+FOXP3+ T regulatory cells (Tregs) from the immature (CD45RA+) to mature (CD45RO+) phenotype has been shown during development and allergic reactions. The relative frequencies of these Treg phenotypes and their responses to oxidative stress during development and allergic inflammation were analysed in samples from paediatric and adult subjects. The FOXP3lowCD45RA+ population was dominant in early childhood, while the percentage of FOXP3highCD45RO+ cells began increasing in the first year of life. These phenotypic changes were observed in subjects with and without asthma. Further, there was a significant increase in phosphorylated ERK1/2 (pERK1/2) protein in hydrogen peroxide (H2O2)-treated CD4+CD25high cells in adults with asthma compared with those without asthma. Increased pERK1/2 levels corresponded with increased Ca2+ response to T cell receptor stimulation. mRNA expression of peroxiredoxins declined in Tregs from adults with asthma. Finally, CD4+CD25high cells from paediatric subjects were more sensitive to oxidative stress than those from adults in vitro. The differential Treg sensitivity to oxidative stress observed in children and adults was likely dependent on phenotypic CD45 isoform switching. Increased sensitivity of Treg cells from adults with asthma to H2O2 resulted from a reduction of peroxiredoxin-2, -3, -4 and increased pERK1/2 via impaired Ca2+ response in these cells.