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Introduction: Circular RNA (circRNA) plays an important role in regulating metabolism of red blood cells (RBCs) and their storage lesions, but the study of how circRNA expression changes in stored RBCs has rarely been conducted. Methods: The expression change of circRNA was systemically evaluated via high-throughput sequencing on healthy RBCs on day 0, 20, and 40. And then we confirmed the reliability of the high-throughput sequencing analysis by RT-qPCR characterization on selected circRNAs. A higher parental gene enrichment was used to explore circRNA function in pathways. In addition, we deciphered a dysregulated circRNA-related ceRNAs network, and identified three circRNA-miRNA-mRNA regulatory axes related to storage lesion. Results: We identified 2,586 known and 6,216 putative novel circRNAs, more than 100 circRNAs expression levels were shifted, and the number of downregulated circRNAs was greater with longer storage time. Furthermore, a higher parental gene enrichment related to circRNA was found in pathways, including cAMP signaling pathway, ubiquitin-mediated proteolysis, apoptosis, adhesion, MAPK signaling pathway, cystine methionine metabolism, RNA degradation, RNA transport, TGF-β, and actin regulatory pathway. hsa_circ_0007127-miR-513a-5p-SMAD4, hsa_circ_0000033-miR-19a-3p-VAMP3, and hsa_circ_0005546-miR-4720-CCND3 regulatory axes related to storage lesion was found. Conclusions: Through investigation in circRNAs profile and circRNA-miRNA-mRNA interactions, this study provides insights on stored RBC circRNA expression changes, which closely relate to the storage lesion of RBCs and their physiological functions. [ABSTRACT FROM AUTHOR]

Immune escape of cancer cells has become the main challenge in the immunocytotherapy field. In this study, we analyzed the cytotoxicity of DC-CIK cells induced by anti-PD-1 and anti-CTLA-4 antibodies in RCC cell lines. Flow cytometry analysis was performed to analyze the immune phenotypes of DC-CIK cells. Click-iT EdU assay was performed to analyze the proliferation of DC-CIK cells. ELISA analysis was performed to detect the expression of cytokines in DC-CIK cells. Compared with DC-CIK cells without any treatment, the growth inhibition rate was significantly higher in the other three groups. Moreover, combined induction with anti-PD-1 plus anti-CTLA-4 antibodies provides synergistic antitumor effects of DC-CIK cells in renal carcinoma cell lines. The combined treatment promoted DC-CIK cell proliferation and differentiation into CD3 + CD56 + NKT cells and CD3 + CD8 + CTL cells. Compared with the control group, combined treatment significantly up-regulated the secretion of immune-stimulatory cytokines, such as IFN-γ and TNF-α, and down-regulated the secretion of the immunosuppressive cytokine IL-10. Furthermore, the co-induction promoted the early activation of DC-CIK cells. These results indicated the co-induction with anti-PD-1 plus anti-CTLA-4 antibodies improved antitumor effects of DC-CIK cells by promoting proliferation, differentiation, and early activation and regulating the secretion of immune-stimulatory and suppressive cytokines in renal carcinoma cell lines., Competing Interests: None., (IJCEP Copyright © 2019.)

Background: The influence of different non-myeloablative conditioning regimens on clinical outcome remains undefined., Material and Methods: We retrospectively analyzed the hematopoietic reconstitution, graft-versus-host disease (GVHD), and quality of life (QOL) in 56 patients with hematologic malignancies who underwent non-myeloablative stem cell transplantation (NST) with a conditioning regimen based on anti-thymocyte globulin (ATG), followed by donor lymphocyte infusion (n=24), or Fludarabine (FLU) (n=32). Hematopoietic stem cells were derived from low-resolution HLA-matched identical sibling donors., Results: The blood type transformation and platelet reconstitution presented significantly earlier in the FLU group than the ATG group (P<0.05). Within 100 days post-transplantation, the incidence of grade I-IV acute GVHD was significantly lower in the ATG group than the FLU group (P<0.05). After 100 days post-transplant, extensive chronic GVHD (cGVHD) was more prevalent in the ATG group than the FLU group (P<0.05). There were lower cumulative risk of relapse and higher non-relapse-related mortality in the ATG group, but better QOL in the FLU group within 24 months, and no difference in 3-year disease-free survival (DFS) or overall survival (OS) between the 2 groups (P>0.05)., Conclusions: The FLU-based conditioning regimen improved hematopoietic reconstitution and decreased extensive cGVHD, but there was no difference in 3-year DFS or OS between the 2 groups.