Plasma Indoleamine 2,3-Dioxygenase Concentration is Increased in Hemodialysis Patients and May Contribute to the Pathogenesis of Coronary Heart Disease

Introduction: Coronary heart disease (CHD) is the leading cause of death in hemodialysis (HD) patients. Inflammation contributes to the pathogenesis of atherosclerosis in this population. Indoleamine 2,3-dioxygenase (IDO), an enzyme with immunomodulatory properties, was evaluated in HD patients with or without CHD. Methods: Of the total of 66 HD patients, 22 of them with CHD were confirmed by coronary angiography and 24 healthy volunteers were enrolled in the study. Plasma IDO was assessed by means of enzyme-linked immunosorbent assay. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) were also measured. Results: Compared with healthy volunteers, plasma IDO concentration was markedly increased in HD patients (median 8.04 ng/mL vs. 48.9 ng/mL). Serum IL-6 and CRP were also significantly increased in HD patients. Compared with HD patients without CHD, plasma IDO concentration was significantly increased in HD patients with CHD (median 38.6 ng/mL vs. 74.5 ng/mL). Neither IL-6 nor CRP differed between the last two groups. IDO was negatively correlated with IL-6 and CRP. Conclusion: IDO concentration is increased in HD patients and is increased further in HD patients with CHD. It remains to be elucidated if increased IDO plays a direct role in the pathogenesis of atherosclerosis or if it affects atherosclerosis indirectly by curtailing chronic inflammation or both

Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children

© 2018 The Author(s). Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD. Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder. 27 families unaffected by cardiovascular disease were also included as controls. Firstly, we screened 84 circulating miRNAs relating to cardiovascular development in 6 children with atrial septal defects (ASD) and 5 healthy children. We validated the selected miRNAs with differential expression in a larger sample size (n = 27 for controls, n = 26 for cases), and evaluated their signal in different types of septal defects. Finally, we examined the identified miRNAs signatures in the parent population and assessed their diagnostic values for predicting CHD. Results: The three miRNAs hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in children with ASD. A further validation study showed that overexpression of hsa-let-7a and hsa-let-7b was specifically present in ASD children, but not in children with other subtypes of septal defects. A similar expression profile of hsa-let-7a and hsa-let-7b was discovered in mothers of ASD children. Receiver-operating characteristic curve analyses indicated that hsa-let-7a and hsa-let-7b had significant diagnostic values for detecting ASD and in maternal samples predicting the occurrence of ASD in offspring. Conclusions: Circulating miRNAs are important markers not only for diagnosing CHD, but also for predicting CHD risk in offspring. The distinct miRNA signatures are likely to present in various subtypes of CHD, and the phenotypic heterogeneity of CHD should be considered to develop such miRNA-based assays

Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells

Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic “universal” cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing