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Introduction: Human leukocyte antigen-G (HLA-G) gene encodes for a tolerogenic molecule constitutively expressed in human pancreas and upregulated upon inflammatory signals. The 14 bp INS/DEL polymorphism in the 3ʹUTR of HLA-G may influence the susceptibility for diabetes and coronary heart diseases (CHD), thus suggesting a novel candidate gene. DNA hypomethylation at HLA-G promoter may be a putative useful clinical biomarker for CHD onset. Upregulation of soluble HLA-G isoform (sHLA-G) was detected in prediabetic and diabetic subjects, suggesting a putative role in metabolic dysfunctions. Areas covered: We conducted a scoping literature review of genetic and epigenetic-sensitive mechanisms regulating HLA-G in diabetes. English-language manuscripts published between 1997 and 2019, were identified through PubMed, Google Scholar, and Web of Science database searches. After selecting 14 original articles representing case-control studies, we summarized and critically evaluated their main findings. Expert commentary: Although epigenetic modifications are involved in the onset of hyperglycemic conditions evolving into diabetes and CHD, it is still difficult to obtain simple and useful clinical biomarkers. Inflammatory-induced KDM6A/INF-β/HLA-G axis might be a part of the epigenetic network leading to overexpression of HLA-G at pancreatic level. Network medicine may show whether HLA-G is involved in diabetes and CHD.

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normalcholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p-value

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value

Innate immune mechanisms are central players in response to the binding of pathogens to pattern-recognition receptors providing a crucial initial block on viral replication. Moreover, innate immune response mobilizes cells of the cellular-mediated immune system, which develop into effector cells that promote viral clearance. Here, we observed circulating leukocyte T cell response in healthy subjects, COVID-19 infected, and in healthy vaccinated subjects. We found a significant CD8+ T cells (p < 0,05) decrease and an augmented CD4+/CD8+ ratio (p < 0,05) in COVID-19 infected group compared with vaccinated subjects. In addition, healthy vaccinated subjects have a significant increased expression of CD8+ T cells, and a reduction of CD4+/CD8+ ratio with respect to subjects previously COVID-19 infected. Central Memory and Terminal Effector Memory cells (TEMRA) increased after vaccine but not among groups.

Objectives: Several donor and recipient factors are known to be associated with graft loss in a kidney transplant. In this retrospective single-center study, we analyzed the effect of clinical and immunologic factors on kidney transplant outcomes in our region in Italy. Materials and Methods: The study included 245 transplanted recipients from deceased donors at Federico II University of Naples, Kidney Transplant Centre, between the years 2000 and 2006. Age, cause of death, history of hypertension, hypotension or cardiac arrest, length of time spent in the intensive care unit, serum creatinine levels and human leukocyte antigen typing all were evaluated in the donors. Age, time spent on the wait list, human leukocyte antigen typing, antibody sensitization, and allocation were evaluated in the recipients. Age, donor/recipient matching, and human leukocyte antigen mismatches also were evaluated. Results: Cox regression analysis showed that in recipients, time spent on the wait list increased the risk of restarting dialysis (OR 1.019, 95% CI: 1.000-1.038; P =.050) and dying (OR 1.017, 95% CI: 1.000-1.038; P =.032). Patients who received a kidney from a donor with a history of hypertension presented a major risk of death (OR 3.212, 95% CI: 1.190-8.668; P =.021), while human leukocyte antigen-A mismatch increased the risk of restarting dialysis (OR 3.137, 95% CI: 1.255-7.842; P =.014). Conclusions: In our study, in recipients, time spent on the wait list, and a history of hypertension were associated with a greater risk of death. Human leukocyte antigen-A mismatch is associated with a greater risk of restarting dialysis.

Background: Despite left ventricular (LV) dysfunction contributing to mortality in chronic heart failure (HF), the molecular mechanisms of LV failure continues to remain poorly understood and myocardial biomarkers have yet to be identified. The aim of this pilot study was to investigate specific transcriptome changes occurring in cardiac tissues of patients with HF compared to healthy condition patients to improve diagnosis and possible treatment of affected subjects. Methods: Unlike other studies, only dilated cardiomyopathy (DCM) (n = 2) and restrictive cardiomyopathy (RCM) (n = 2) patients who did not report family history of the disease were selected with the aim of obtaining a homogeneous population for the study. The transcriptome of all patients were studied by RNA-sequencing (RNA-Seq) and the read counts were adequately filtered and normalized using a recently developed user-friendly tool for RNA-Seq data analysis, based on a new graphical user interface (RNA-SeqGUI). Results: By using this approach in a pairwise comparison with healthy donors, we were able to identify DCM- and RCM-specific expression signatures for protein-coding genes as well as for long noncoding RNAs (lncRNAs). Differential expression of 5 genes encoding different members of the mediator complex was disclosed in this analysis. Interestingly, a significant alteration was found for genes which had never been associated with HF until now, and 27 lncRNA/mRNA pairs that were significantly altered in HF patients. Conclusions: The present findings revealed specific expression pattern of both protein-coding and lncRNAs in HF patients, confirming that new LV myocardial biomarkers could be reliably identified using Next-Generation Sequencing-based approaches.

Endothelial progenitor cells (EPCs) play a role in endogenous neovascularization of ischaemic tissues. Isolation and characterization of EPCs from circulating mononuclear cells are important for developing targeted cellular therapies and reproducibility of data are the major scientific goals. Here we compared two currently employed isolation methods, i.e. from total peripheral blood mononuclear cells (PBMCs) and from enriched CD133+ cells, by defining the cell morphology and functional activities. We show that EPCs from cultured PBMCs resulted in an adherent population of 23% ± 4% merged cells positive for Dil-Ac-LDL and lectin, whereas the percentage of double positive cells in cultured CD133+ enriched cells was 50% ± 7% (P < 0.01). These data were obtained through a novel and a more complete method of analysis of cell calculations (specifically by dividing each microscope field into 120 subfields). When stimulated with tumour necrosis factor α (TNF)-α and glucose, cell number was reduced in EPCs from total PBMCs and, more consistently, in CD133+ enriched cells. However, both cultured total PBMCs and CD133+ enriched cells respond similarly to TNF-α or glucose-induced p38-phosphorylation.EPCs from both procedures show similar results in terms of phenotype and response to modulators of their functional activities. However, when the cell phenotype of CD133 + enrichment-derived cells was compared with that of cells from the total PBMC, a significant increase in CD133+ expression was observed (P < 0.01) This may have relevance during intervention studies using cultured EPCs. © 2007 The Japanese Biochemical Society.

""The CD146 cell membrane adhesion molecule is highly expressed on the cell surface of several tumours. The level of its expression has been found to correlate directly with tumour progression and metastatic potential, thus establishing CD146 as an important candidate of tumour growth and metastasis. In order to characterize its expression in human osteosarcoma (OS) cell lines, we have examined the CD146 expression at protein and RNA levels in both normal and tumour osteoblast-like cell lines by several methods. Our results indicate that CD146 protein is expressed at low levels in normal osteoblast cells whereas it is highly expressed in all OS cell lines analysed, (SaOS, MG-63, U-2OS). Moreover, CD146 overexpression was partially reduced in shYY1 cells, where the Yin Yang 1 transcription factor, also found over-expressed in human OS cells, has been silenced""

"The participation in the external proficiency testing (EPT) workshops gives the opportunity to verify HLA typing results of a laboratory. comparing and analyzing its results with other participants. In 1996, the Regional Reference Laboratory of Transplant Immunology (LIT). of Campania started to the Quality Control for Regional HLA typing labs (CQR) working in the field of Organ and \/ or Stem Cells. Transplantation. Initially, the number of laboratory participants for serological HLA typing was 6. Later, more laboratories were involved.. The success of regional trials prompted us, as also requested from Mayor Institute of Health (ISS) and Italian National Transplant Center,. to expand the activity to the southern Italian regions, involving together with Campania also Calabria, Puglia and Sicilia. Information and. invitation letters were sent to 24 laboratories of southem Italy involved in HLA typing for The Proficiency Testing of HLA Class I & II.. Separate schemes have been provided for the three techniques routinely used: complement-dependent cytotoxicity (CDC), DNA low. resolution and, since 2009, high resolution only for DRB1. All samples submitted were selected to cover all the most common antigens.. In each trail each laboratory has been given a lab.code. Since the results of the first two years were heterogeneous and incomplete for most of the participants, the LIT decided not to proceed with the evaluation, and considered it as a mere exercise. Since 2000, we have. adopted the guidelines of EFI and ISS for HLA typing EPT. One discrepancy was considered as the maximum number allowed for each. technique. Most labs had problems with HLA-C and -DQ locus typing. They could not type antigens of these loci. From 1996 to 2010 all. the data have been analyzed at LIT and the results discussed versus the consensus typing. The participants have also received the. summary of all submitted results followed by an appropriate certificate, necessary for EFI accreditation."

Objectives: The relevance of anti-HLA antibodies in patients awaiting kidney transplants is well recognized. During the past 40 years, kidney transplant candidates have been tested for these antibodies, and the choice of the detection assay has become essential. Recently, the pioneer method, the complement-dependent cytotoxicity, has been integrated but has not been replaced by more-sensitive solid-phase assays, such as the enzyme-linked immunosorbent assay and the bead-based technology (ie, flow cytometry: FlowPRA, and Flow Analyzer: Luminex). Materials and Methods: We compared the sensitivity and antibody specificity of these 4 techniques for detecting panel-reactive antibodies in a population of 101 consecutive patients awaiting a renal transplant (which had already resulted positive in a prescreening analysis). Results: Sera positive for class I and class II antibodies were 62 and 90 as assessed by the complement-dependent cytotoxicity method, 76 and 58 by using enzyme-linked immunosorbent assay, 83 and 65 with Flow-panel-reactive antibodies, and 90 and 79 by Luminex. Luminex gave more positive scores than the others for class I HLA antibodies, whereas complement-dependent cytotoxicity revealed more positives for those of class II. Conclusions: Although Luminex appears more efficient among these assays, our results indicate that use of multiple methods is still the best approach for characterizing the immunologic status of these patients.