Inhibition of influenza virus replication in cultured cells by RNA-cleaving DNA enzyme

AbstractInfluenza virus replication has been effectively inhibited by antisense phosphothioate oligonucleotides targeting the AUG initiation codon of PB2 mRNA. We designed RNA-cleaving DNA enzymes from 10-23 catalytic motif to target PB2-AUG initiation codon and measured their RNA-cleaving activity in vitro. Although the RNA-cleaving activity was not optimal under physiological conditions, DNA enzymes inhibited viral replication in cultured cells more effectively than antisense phosphothioate oligonucleotides. Our data indicated that DNA enzymes could be useful for the control of viral infection

Safe and efficient method for cryopreservation of human induced pluripotent stem cell-derived neural stem and progenitor cells by a programmed freezer with a magnetic field

AbstractStem cells represent a potential cellular resource in the development of regenerative medicine approaches to the treatment of pathologies in which specific cells are degenerated or damaged by genetic abnormality, disease, or injury. Securing sufficient supplies of cells suited to the demands of cell transplantation, however, remains challenging, and the establishment of safe and efficient cell banking procedures is an important goal. Cryopreservation allows the storage of stem cells for prolonged time periods while maintaining them in adequate condition for use in clinical settings. Conventional cryopreservation systems include slow-freezing and vitrification both have advantages and disadvantages in terms of cell viability and/or scalability. In the present study, we developed an advanced slow-freezing technique using a programmed freezer with a magnetic field called Cells Alive System (CAS) and examined its effectiveness on human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs). This system significantly increased cell viability after thawing and had less impact on cellular proliferation and differentiation. We further found that frozen-thawed hiPSC-NS/PCs were comparable with non-frozen ones at the transcriptome level. Given these findings, we suggest that the CAS is useful for hiPSC-NS/PCs banking for clinical uses involving neural disorders and may open new avenues for future regenerative medicine

Effects of hydrophilic polymer-coated polysulfone membrane dialyzers on intradialytic hypotension in diabetic hemodialysis patients (ATHRITE BP Study) : a pilot study

Background: Intradialytic hypotension (IDH) is a common clinical manifestation associated with poor prognosis in hemodialysis (HD) patients. HD patients who suffer from diabetic nephropathy (DN) are increasing and diabetes is a major cause of IDH. Effective interventional treatments for IDH have yet to be fully evaluated. The aim of this multicenter prospective study is to clarify the effect of biocompatible hydrophilic polymer-coated polysulfone (PS) membrane, TORAYLIGHT® NV (NV) dialyzers on IDH. Methods: This is a prospective stratified-randomized multicenter trial. Forty DN patients undergoing HD and receiving two or more times of treatments for IDH per month were enrolled in this study. They were stratified by the number of treatments for IDH and divided to two groups using NV or conventional PS/polyethersulfone (PES) dialyzers. The number of treatments for IDH and changes in systolic blood pressure (SBP) were monitored for 6 months. Patients’ demographic and clinical characteristics were also collected at enrollment and the last month of the observation period. In order to clarify the patient characteristics that induced preferable effects by using NV dialyzers, responders were defined as the patients whose average SBP falls in 1 month improved from over 30 mmHg to no more than 30 mmHg. Results: The total number of treatments for IDH decreased significantly in NV group, even though pre-dialysis body weight and ultrafiltration volume were similar. In addition, patients using NV had significantly higher post-dialysis SBP and the lowest SBP during HD at sixth month compared as those in PS/PES group. NV responders had valuables suggesting malnutrition and microinflammation, and better lipid profiles than non-responders. However, the representative markers related to nutritional status, arteriosclerosis, and inflammation were not improved by NV treatment. Conclusions: NV had preferable effects on IDH in DN HD patients. Our results suggest the usefulness of NV as a possible method to deal with IDH. Further studies are needed to clarify the mechanism of NV effects on hemodynamic status

Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma

Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBVencoded RNA.We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-a, and arginase 1, suggesting the immune regulatory role of BART miRNAs.The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma.These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV1 B-cell lymphoma. (Blood. 2018;131(23):2552-2567)

Clozapine and Antipsychotic Monotherapy

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription