Valutazione del potenziale angiogenico di cellule mesenchimali staminali adulte derivate dalla polpa dentaria umana

Dental pulp has been revealed as an accessible and a rich source of mesenchymal stem cells (MSCs) and its biological potential is currently under intense investigation. MSCs from dental pulp stem cells (DPSC) have been indicated as a heterogeneous population oriented not only in repairing dentine but also in maintaining vascular and nervous homeostasis of the teeth. We sought to verify the phenotype of cells isolated from dental pulp of young donors and to investigate in vitro their role as pericyte-like cells. Specifically, we evaluated how different culture conditions can modulate expression of pericyte markers in DPSC and their capacity to stabilize endothelial tubes in vitro. DPSC cultured in standard conditions expressed MSC markers and demonstrated to contain a population expressing the pericyte marker NG2. These DPSC were associated with low sprouting capacity in extracellular (EC) Matrix and limited ability in retaining tubes formed by endothelial cells in a coculture angiogenesis model. When cultured in endothelial growth medium (EGM-2), DPSC significantly upregulated NG2. The resulting population conserved the stem marker CD73 but was negative for calponin and endothelial markers. EGM-2-conditioned DPSC showed a higher sprouting ability in EC Matrix and efficient association with human umbilical vein endothelial cells allowing the partial retention of endothelial tubes for several days. Among growth factors contained in EGM-2 we identified basic fibroblast growth factor (FGF) as mainly responsible for NG2 upregulation and long-term stabilization of endothelial tubes. According to the in vitro analysis, DPSC represent an effective source of pericytes, and the appropriate culture conditions could result in a population with a promising ability to stabilize vessels and promote vascular maturation

Role of Prion protein-EGFR multimolecular complex during neuronal differentiation of human dental pulp-derived stem cells

Cellular prion protein (PrPC) is expressed in a wide variety of stem cells in which regulates their self-renewal as well as differentiation potential. In this study we investigated the presence of PrPCin human dental pulp-derived stem cells (hDPSCs) and its role in neuronal differentiation process. We show that hDPSCs expresses early PrPCat low concentration and its expression increases after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of PrPCwith gangliosides and EGF receptor (EGF-R) during neuronal differentiation process. PrPCassociates constitutively with GM2 in control hDPSCs and with GD3 only after neuronal differentiation. Otherwise, EGF-R associates weakly in control hDPSCs and more markedly after neuronal differentiation. To analyze the functional role of PrPCin the signal pathway mediated by EGF/EGF-R, a siRNA PrP was applied to ablate PrPCand its function. The treatment with siRNA PrP significantly prevented Akt and ERK1/2 phosphorylation induced by EGF. Moreover, siRNA PrP treatment significantly prevented neuronal-specific antigens expression induced by EGF/bFGF, indicating that cellular prion protein is essential for EGF/bFGF-induced hDPSCs differentiation. These results suggest that PrPCinteract with EGF-R within lipid rafts, playing a role in the multimolecular signaling complexes involved in hDPSCs neuronal differentiation

Low-density lipoprotein-lowering medication and platelet function

Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) levels represent one of the most important risk factors for atherosclerosis and therefore cardiovascular morbidity and mortality. LDL-C operates at different levels and through various classic and non-classic mechanisms. In particular, increased or modified LDL enhances platelet function and increases sensitivity of platelets to several naturally occurring agonists. Agents that lower LDL-C in hypercholesterolemic patients have been shown to interfere with platelet function. Several studies, in fact, suggested that statins exert anti-thrombotic effects largely as a result of an anti-platelet activity. Among the other LDL-C-lowering agents those acting by interfering with cholesterol reabsorption from the gut (cholestyramine, colestipol) do not appear to interfere with platelet function, whereas peroxisome proliferator-activated receptor agonists (such as fibrates) can inhibit platelet function. The full potential of these drugs in vascular protection is only just being realized. Further studies are still needed to elucidate the full therapeutic benefits of these agents in plaque stabilization and thrombosis. Copyright (c) 2006 S. Karger AG, Basel

Inflammation, platelets and diabetes

Type 2 diabetes is a key player in atherothrombosis. Inflammation participates in metabolic homeostasis interacting with adipose tissue-specific macrophages. Platelets appear as addresses and players carrying and transducing metabolic derangement into vascular injury. AGE-RAGE pathway is recognized as the driver of metabolic memory. Human platelets have insulin receptors that participate in the regulation of platelet function and platelets are potential sites of insulin resistance. The present mini-review addresses key pathophysiological aspects including i) the role of inflammation in the pathogenesis of diabetes; ii) platelets as inflammatory cells; iii) the involvement on inflammation in the interindividual variability in aspirin response. Taken together, these aspects may contribute to expand knowledge about the link between the extent of inflammation, platelet activation and turnover, and interindividual variability in the development of atherothrombosis and its prevention, in a view of precision medicine

Cancer mortality trend in central Italy. focus on a “low rate of land use” area from 1982 to 2011

The aim of the present study was to estimate total cancer mortality trends from 1982 to 2011 in a “low rate of land use” province of the Latium region (Rieti, central Italy) characterized by a low degree of urbanization, a high prevalence of elderly, and a low number of births. Mortality data of the studied period, provided by the Italian National Institute of Statistics, were used for calculating standardized cancer mortality rates. Trends in mortality were analyzed using Joinpoint regression analysis. Results showed that total standardized cancer mortality rates decreased in the monitored area over the study period. A comparison with other provinces of the same region evidenced that the studied province presented the lowest cancer mortality. The three systems/apparatuses affected by cancer that mainly influenced cancer mortality in the monitored province were the trachea-bronchus-lung, colorectal-anus, and stomach. These findings could be attributed to the implement of preventive initiatives performed in the early 2000s, to healthier environmental scenario, and to lower levels of carcinogenic pollutants in air, water, and soil matrices. Thus, our results indicate that the studied area could be considered a “healthy” benchmark for studies in oncological diseases

Insulin resistance as a determinant of platelet activation in obese women

OBJECTIVES We tested the hypothesis that insulin resistance, per se, contributes to increased platelet activation in obesity, independently of underlying inflammation. BACKGROUND Obesity, insulin resistance, and atherosclerosis are closely linked phenomena associated with low-grade inflammation. Obesity is associated with persistent platelet activation in otherwise healthy women. METHODS We performed a cross-sectional study in 40 obese and 20 non-obese healthy women using urinary thromboxane metabolite excretion as a non-invasive index of platelet activation. An index of insulin sensitivity, S, and plasma adiponectin, C-reactive protein (CRP), and CD40 ligand (CD40L) levels were measured. RESULTS Obese women had significantly (p < 0.0001) higher 11-dehydro-thromboxane B-2 (11-dehydro-TXB2) excretion (median 718 vs. 211 pg/mg creatinine), CRP (1.13 vs. 0.48 mg/1), and CD40L levels (4.45 vs. 0.90 ng/ml) than controls. Obese women had lower S, (median 2.51 vs. 5.0 10(4) min(-1)/[mu U/ml], p < 0.002) and adiponectin (6.3 vs. 10 mu g/ml, p < 0.01) than control subjects. On multiple regression analysis, waist-to-hip ratio (beta = 0.27, p < 0.05) and S, (beta = -0.72, p < 0.04) predicted 11-dehydro-TXB2 excretion rate, independently of adiponectin, CRP, CD40L, and lipid patterns. In order to investigate the cause-effect relationship of these associations, we examined the effects of a 12-week weight loss program or a 3-week pioglitazone treatment on urinary 11-dehydro-TXB2 in 10 women with impaired S-1 and visceral obesity. Successful weight loss (0.6 kg loss/week) achieved in 5 subjects was associated with increased S-1 (+92%) and decreased CD40L (-27%), CRP (-37%), and 11-dehydro-TXB2 (-53%) (p < 0.05). Consistently, improvement of insulin sensitivity achieved with pioglitazone significantly decreased urinary 11-dehydro-TXB2 excretion (-43%, p < 0.05) without changes in body weight. CONCLUSIONS Insulin resistance is a major determinant of platelet activation in female obesity

Could ischemic colitis be the first manifestation of COVID-19? A case report

We report on a case of SARS-CoV-2-infected patient with clinical and histologic features mimicking ischaemic colitis. This case provides evidence that SARS-CoV-2 may compromise the microvascular blood flow in the intestinal wall, with a parallel activation of the inflammatory cascade, either in the absence, or earlier of any pulmonary involvement

A Case of Coinfection with SARS-COV-2 and Cytomegalovirus in the Era of COVID-19

The World Health Organization has declared novel coronavirus disease 2019 (COVID-19) an international public health emergency. We describe the case of a 92-year-old woman who was admitted to our unit with fever and chills with laboratory evidence of coinfection with SARS-CoV-2 and cytomegalovirus

Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients

Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a potential correlation between Tyrosine Kinase Inhibitors (TKIs) treatment and CV events. One hundred and 10 chronic phase CML patients in complete cytogenetic response during nilotinib or imatinib, were screened for CV events and evaluated for: traditional CV risk factors, pro/anti-inflammatory biochemical parameters and detrimental ORL1 gene polymorphisms (encoding for altered oxidized LDL receptor-1). Multivariate analysis of the whole cohort showed that the cluster of co-existing nilotinib treatment, dyslipidaemia and G allele of LOX-1 polymorphism was the only significant finding associated with CV events. Furthermore, multivariate analysis according to TKI treatment confirmed IVS4-14 G/G LOX-1 polymorphism as the strongest predictive factor for a higher incidence of CV events in nilotinib patients. Biochemical assessment showed an unbalanced pro-inflammatory cytokines network in nilotinib vs imatinib patients. Surprisingly, pre-existing traditional CV risk factors were not always predictive of CV events. We believe that in nilotinib patients an induced "inflammatory/oxidative status", together with a genetic pro-atherothrombotic predisposition, may favour the increased incidence of CV events. Prospective studies focused on this issue are ongoing

Neurological features of COVID-19 infection: A case series of geriatric patients

The coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which is responsible for the coronavirus disease 2019 (COVID-19), is known to cause substantial pulmonary disease. However, clinicians observed many extrapulmonary manifestations of COVID-19. Neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of central nervous system disease caused by SARS-CoV-2 might be expected to be rare. We report four cases of neurologic manifestations of SARS-CoV-2 in elderly patients who presented to the Geriatric Department of Pescara Hospital (Italy)