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

Non-dipper blood pressure pattern and glycemic alterations: does post-prandial glucose rise predict lack of nocturnal pressure drop?

Type 2 diabetes (T2DM) and non-dipping pattern of blood pressure (that is, when nocturnal systolic blood pressure falls by < 10% from the daytime systolic blood pressure values) during 24-h ambulatory blood pressure (ABPM) monitoring are two factors both increasing the risk for cardiovascular disease. Little is known about the relationship between the circadian profile of blood pressure dipping pattern and insulin glucose metabolism in patients without any known overt metabolic diseases

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

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

Is there a rationale for supplementing with vitamin D patients under treatment with allergen immunotherapy?

Vitamin D (VD) has been shown to exert immunomodulatory activities, especially in promoting immune tolerance. For these properties VD has been proposed in the therapy of immunological conditions in which the loss of tolerance is the key pathogenetic aspect of the disease, such as allergies. Despite these properties available literature suggests VD is not useful in treating or preventing allergic diseases and whether low serum VD levels favor allergic sensitization and severity is debated. The level of VD is one of the many conditions that can influence allergic sensitization and therefore only a multivariate analysis on a numerically adequate cohort of patients, that considers all the factors that can favor allergy, would be able to assign the weight of each variable and determine the extent to which VD inhibits allergic sensitization and march. On the contrary, VD is able to potentiate the antigen-specific tolerogenic response induced by Allergen Immunotherapy (AIT) as demonstrated by the large majority of studies. In our experience, the association of VD and Sublingual AIT (LAIS, Lofarma, Italy) gave an excellent clinical and immune response in particular enhancing the differentiation of memory T regulatory cells. While waiting for a more extensive literature, VD/AIT combination should be always performed in treating allergies. In any case, the assessment of the level of VD should become a routine in allergic patients with an indication to AIT as, in case of VD deficiency or insufficiency, VD seems a particularly active adjuvant to the immune treatment

Implications of the heterogeneity between guideline recommendations for the use of low dose aspirin in primary prevention of cardiovascular disease

The most recent primary cardiovascular disease (CVD) prevention clinical guidelines used in Europe, Italy, the USA, China, and South Korea differ in aspects of their approach to CVD risk assessment and reduction. Low dose aspirin use is recommended in certain high-risk patients by most but not all the countries. Assessment of traditional risk factors and which prediction models are commonly used differ between countries. The assessments and tools may not, however, identify all patients at high risk but without manifest CVD. The use of coronary artery calcium (CAC) score to guide decisions regarding primary prevention aspirin therapy is recommended only by the US primary prevention guidelines and the 2021 European Society of Cardiology guidelines. A more consistent and comprehensive global approach to CVD risk estimation in individual patients could help to personalize primary CVD prevention. Wider detection of subclinical atherosclerosis, together with structured assessment and effective mitigation of bleeding risk, may appropriately target patients likely to gain net benefit from low dose aspirin therapy