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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.

Aims Insulin pump failure and/or malfunction requiring replacement have not been thoroughly investigated. This study evaluated pump replacement in children and adolescents with Type 1 diabetes using insulin pump therapy. Methods Data were collected for all participants younger than 19 years, starting insulin pump therapy before 31 December 2013. For each child, age, disease duration, date of insulin pump therapy initiation, insulin pump model, failure/malfunction/replacement yes/no and reason were considered for the year 2013. Results Data were returned by 40 of 43 paediatric centres belonging to the Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type 1 diabetes were using an insulin pump: 29.2% Animas VIBE™, 9.4% Medtronic MiniMed 715/515™, 34.3% Medtronic MiniMed VEO™, 24.3% Accu-Check Spirit Combo™ and 2.8% other models. In 2013, 0.165 insulin pump replacements per patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental damage) were recorded. Animas VIBE™ (22.1%) and Medtronic MiniMed VEO™ (17.7%) were the most replaced. Conclusions In a large cohort of Italian children and adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent replacement are aligned with rates previously reported and higher in more sophisticated pump models. This article is protected by copyright. All rights reserved.

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.

Intravesical gemcitabine has been tested in several phase I studies. The 2000 mg dose of gemcitabine in 50/100 ml normal saline when administered intravesically for up to 2 hours once a week for 6 weeks has unremarkable systemic and local side effects and therefore should be considered the most convenient schedule. Phase II studies have assessed the activity of intravesical gemcitabine on a marker lesion in intermediate risk non-muscle invasive bladder cancer (NMIBC), showing complete responses in up to 60% of cases. Few attempts have been made to test the activity of intravesical gemcitabine in high risk NMIBC achieving unexpected complete responses in BCG refractory CIS. Initial trials have also documented "clinically relevant" responses in prophylaxis. The current level of evidence indicates that gemcitabine possesses clinical activity but further confirmation is awaited from additional exploratory phase II and preferably phase III trials.

Neuroendocrine bladder cancer is extremely rare, with an estimated incidence of 0.5%- 0.7%. In bladder cancers there is no evident connection between the neuroendocrine phenotypic expression and the clinical history. However, prognosis is usually poor and the survival rate at 5 years does not exceed 8%, if untreated. METHODS. We are here describing three case reports of bladder carcinoma with neuroendocrine differentiation, which is extremely aggressive and leads rapidly to death. At the present time, the local control of these tumors is achieved by radical cystectomy and radiotherapy; they can be both associated to chemotherapy. However, since these lesions are fairly rare, there is no gold standard therapy and there are no prospective studies on the management of these tumors. CONCLUSIONS. Considering the quick evolution and progression of any variant of the neuroendocrine tumors of the bladder, urologists and anesthetists should see them as real oncological emergencies. A prompt intervention through radical surgery with cystectomy and linfadenectomia, and the anathomo-pathologist's systematic investigation of the scraps could make the approach therapeutic and not only palliative. Prospective studies on neo-adjuvant chemotherapy as well as experimental studies about target therapies may yield new guidelines on the tumor management.

Hematopoietic stem cells derive regulatory information also from parathyroid hormone (PTH). To explore the possibility that PTH may have a role in regulation of other stem cells residing in bone marrow, such as mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) we assessed the effect of this hormone on the in vitro behavior of MSCs and EPCs. Weevidenced that MSCs were much more responsive to PTH than EPCs. PTH increased the proliferation rate of MSCs with a diminution of senescence and apoptosis. Taken together, our results may suggest a protective effect of PTH on MSCs that reduces stress phenomena and preserve genome integrity. At the opposite, PTH did not modify the fate of EPCs in culture. © 2009 Wiley-Liss, Inc.

Alteration of levels and functional activities of circulating endothelial progenitor cells (EPCs) induced by risk factors for coronary heart disease (CHD) profoundly influence their role in the regeneration of tissue ischemia and angiogenesis. Among antioxidant nutrients in the prevention of CHD, L-arginine is particularly effective in enhancing the protection afforded by moderate physical exercise. Here, we aimed to evaluate the effects of L-arginine on EPC levels in C57BL/6J mice subjected to moderate physical exercise. Results showed that supplementation with L-arginine potentiates the effects of moderate physical exercise by increasing significantly EPCs (P

Background The development of alloantibodies may complicate the management of patients with β-thalassemia. An extended antigenic matching may reduce the risk of alloimmunization. Our previous study showed that the introduction of molecular red blood cell (RBC) typing allows finding suitable blood units for multi-transfused patients. The aim of this study was to evaluate the benefit of RBC transfusion with extended antigenic match. Materials and methods At the University of Campania “L. Vanvitelli”, we selected β-thalassemia major patients (age ≤23 years), without preformed alloantibodies. Data of patients receiving transfusion of leukoreduced RBC units for a period of one year with partial better match (PBM) including ABO, RhD, C/c, E/e, K/k antigens and consecutive one year with extended match (EM) including ABO, RhD, C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, S/s antigens, were compared. Results Eighteen patients, 8 males and 10 females with a mean age of 15.4 years (6.4 SD) received a mean number of 41.2 (6.0 SD) RBC units transfused with PBM and 41.8 (6.2 SD) with EM protocols. After two years of RBC transfusions with both antigen matching protocols, no new alloantibodies were developed in patients. No significant differences in Hb concentration and volume of RBC transfused were found between PBM and EM protocols. Conclusions Thalassemia patients may benefit from receiving RBC transfusions based on extended antigen matching as demonstrated by the lack of new alloantibodies. However, our data show a high concordance between PBM and EM protocols considering pre-transfusion Hb, increment of Hb and volume of RBC transfused.

Aim Hyperglycemia status induces endothelial dysfunction, although the underlying pathogenic mechanisms are not fully understood. There are several studies connecting sugar/sweetened beverages to the cardiovascular disease. Currently, many sweeteners have been extensively introduced into lifestyle to normalize blood glucose levels without altering the sweet taste. However, there is growing concern for their impact on metabolic health. Methods Human endothelial cells were treated with Glucose, Fructose, Aspartame, Rebaudioside A, Stevioside, or Steviol. Morphological characteristics, in vitro angiogenesis and array gene expression were analyzed. Results High-glucose and fructose concentrations significantly decreased cell features such as angiogenic capability. Interestingly, non-caloric sweeteners did not significantly modified all cell characteristics and they did not compromised cell angiogenic ability. Array gene expression analysis revealed that the chemokine fractalkine (CX3CL1) and the enzyme transferase (HPRT1) were always significantly upregulated and downregulated respectively, after glucose and fructose treatments (P > .05), whereas they were non-differentially expressed with all the other sweeteners. Interestingly, both genes are considered as cardiovascular disease risk biomarkers. Specifically, upregulation of CX3CL1/CX3CR1 occurs in the human placenta and serum levels of the ligand are associated with markers of insulin resistance in GDM. Conclusions Differently from glucose and fructose, steviol glycosides do not damage endothelial cells. Prospective preclinical studies and clinical trials are warranted to confirm the long-term safety of such compounds.