Nutraceuticals and their role in tumor angiogenesis

Angiogenesis plays a pivotal role in cancer initiation, maintenance, and progression. Diet may inhibit, retard or reverse these processes affecting angiogenesis (angioprevention). Nutraceuticals, such as omega-3 fatty acids, amino acids, proteins, vitamins, minerals, fibers, and phenolic compounds, improve health benefits as they are a source of bioactive compounds that, among other effects, can regulate angiogenesis. The literature concerning the pro-angiogenic and/or anti-angiogenic nutraceuticals and the possible activated pathways in cancer and other non-neoplastic diseases by in vivo and in vitro experiments are reviewed

Involvement of vascular endothelial growth factor in schizophrenia

Vascular endothelial growth factor (VEGF), which acts as an angiogenic and neurotrophic factor, is involved the regulation of cerebral blood volume and flow in Schizophrenia (SCZ). Several evidence indicates that modification of brain blood circulation due to alterations in the VEGF system affects cognitive performance and brain function in patients with SCZ. The aim of this study is: 1) To analyze the literature data concerning the role of VEGF in modulating the angiogenic response in SCZ. These data are controversial because some studies found elevated VEGF serum levels of VEGF in patients with SCZ, whereas others demonstrated no significant differences between SCZ patients and controls. 2)To analyze the role of VEGF as a predictive factor on the effects of antipsychotics agents used in the treatment of SCZ. In this context, high VEGF levels, associated to better responses to antipsychotics, might be predictive of the use of first generation antipsycotic drugs, whereas low VEGF levels, expression of resistance to therapy, might be predictive for the use of second generation antipsycotic drugs

Different spatial distribution of inflammatory cells in the tumor microenvironment of ABC and GBC subgroups of diffuse large B cell lymphoma

Diffuse Large B-Cell Lymphoma (DLBCL) presents a high clinical and biological heterogeneity, and the tumor microenvironment chracteristics are important in its progression. The aim of this study was to evaluate tumor T, B cells, macrophages and mast cells distribution in GBC and ABC DLBCL subgroups through a set of morphometric parameters allowing to provide a quantitative evaluation of the morphological features of the spatial patterns generated by these inflammatory cells. Histological ABC and GCB samples were immunostained for CD4, CD8, CD68, CD 163, and tryptase in order to determine both percentage and position of positive cells in the tissue characterizing their spatial distribution. The results evidenced that cell patterns generated by CD4-, CD8-, CD68-, CD163- and tryptase-positive cell profiles exhibited a significantly higher uniformity index in ABC than in GCB subgroup. The positive-cell distributions appeared clustered in tissues from GCB, while in tissues from ABC such a feature was lower or absent. The combinations of spatial statistics-derived parameters can lead to better predictions of tumor cell infiltration than any classical morphometric method providing a more accurate description of the functional status of the tumor, useful for patient prognosis

PB2064 USE OF RNASCOPE TECHNOLOGY TO DETERMINE STAT-3 EXPRESSION IN HUMAN DIFFUSE LARGE B-CELL LYMPHOMA

Diffuse large B-cell lymphoma (DLBCL) is the most common and one of the most heterogeneous lymphomas. Therefore, it is critical to further stratify cases of DLBCL into biologically similar and clinically meaningful subgroups, which will not only guide prognostic assessment and facilitate therapeutic decisions, but also stimulate further research to understand the pathogenesis and develop potential novel treatments. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that exerts important biological functions related to cell proliferation, differentiation, survival, angiogenesis and immune response

A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

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PTX3 shapes profibrotic immune cells and epithelial/fibroblast repair and regeneration in a murine model of pulmonary fibrosis

The long pentraxin 3 (PTX3) is protective in different pathologies but was not analyzed in-depth in Idiopathic Pulmonary Fibrosis (IPF). Here, we have explored the influence of PTX3 in the bleomycin (BLM)-induced murine model of IPF by looking at immune cells (macrophages, mast cells, T cells) and stemness/regenerative markers of lung epithelium (SOX2) and fibro-blasts/myofibroblasts (CD44) at different time points that retrace the progression of the disease from onset at day 14, to full-blown disease at day 21, to incomplete regression at day 28. We took advantage of transgenic PTX3 overexpressing mice (Tie2-PTX3) and Ptx3 null ones (PTX3-KO) in which pulmonary fibrosis was induced. Our data have shown that PTX3 overexpression in Tie2-PTX3 compared to WT or PTX3-KO: reduced CD68+ and CD163+ macrophages and the Tryptase+ mast cells during the whole experimental time; on the contrary, CD4+ T cells are consistently present on day 14 and dramatically decreased on day 21; CD8+ T cells do not show significant differences on day 14, but are significantly reduced on day 21; SOX2 is reduced on days 14 and 21; CD44 is reduced on day 21. Therefore, PTX3 could act on the proimmune and fibrogenic microenvironment to prevent fibrosis in BLM-treated mice

STAT3, tumor microenvironment, and microvessel density in diffuse large B cell lymphomas

Constitutively activated STAT3 is correlated with more advanced clinical stage and overall poor survival of diffuse large B-cell lymphoma (DLBCL). The aim of this study was to evaluate STAT3 and Ki67 tumor cell expression, inflammatory cell infiltration, microvascular density in DLBCL bioptic specimens. RNA-scope showed that activated B cell (ABC) tissue samples contained a significant higher number of STAT3+ cells as compared to germinal center B (GCB) tissue samples. Immunohistochemical analysis showed a significant increased levels of CD3, CD8, CD68, CD163, CD34, and Ki67 positive cells in ABC patients. A positive correlation between STAT3 and CD3, CD8, CD68, and CD163 was evidenced in ABC group. In ABC group, we found also a positive correlation between CD8 and CD34 and a positive correlation between Ki67 and, CD68, and CD163. These data indicate that in ABC—as compared to GCB-DLBCL, a higher STAT3 expression is associated with a higher CD163+ TAM and CD8+ cell infiltration which induces a strong angiogenic response

Dp71 expression in human glioblastoma

Background: Dp71 is the most abundant dystrophin (DMD) gene product in the nervous system. Mutation in the Dp71 coding region is associated with cognitive disturbances in Duchenne muscular dystrophy (DMD) patients, but the function of dystrophin Dp71 in tumor progression remains to be established. This study investigated Dp71 expression in glioblastoma, the most common and aggressive primary tumor of the central nervous system (CNS). Methods: Dp71 expression was analyzed by immunofluorescence, immunohistochemistry, RT-PCR, and immunoblotting in glioblastoma cell lines and cells isolated from human glioblastoma multiforme (GBM) bioptic specimens. Results: Dp71 isoform was expressed in normal human astrocytes (NHA) cell lines and decreased in glioblastoma cell lines and cells isolated from human glioblastoma multiforme bioptic specimens. Moreover, Dp71 was localized in the nucleus in normal cells, while it was localized into the cytoplasm of glioblastoma cells organized in clusters. We have shown, by double labeling, that Dp71 colocalizes with lamin B in normal astrocytes cells, confirming the roles of Dp71 and lamin B in maintaining nuclear architecture. Finally, we demonstrated that decreased Dp71 protein in cells isolated from human bioptic specimens was inversely correlated with the Ki-67 tumor proliferative index. Conclusion: A decreased Dp71 expression is associated with cancer proliferation and poor prognosis in glioblastoma

Discontinuous Transition from a Real Bound State to Virtual Bound State in a Mixed-Valence State of SmS

Golden SmS is a paramagnetic, mixed-valence system with a pseudogap. With increasing pressure across a critical pressure Pc, the system undergoes a discontinuous transition into a metallic, anti-ferromagnetically ordered state. By using a combination of thermodynamic, transport, and magnetic measurements, we show that the pseudogap results from the formation of a local bound state with spin singlet. We further argue that the transition Pc is regarded as a transition from an insulating electron-hole gas to a Kondo metal, i.e., from a spatially bound state to a Kondo virtually bound state between 4f and conduction electrons.Comment: 5 pages, 5 figure

Defining the role of NG2-expressing cells in experimental models of multiple sclerosis. A biofunctional analysis of the neurovascular unit in wild type and NG2 null mice

During experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis associated with blood-brain barrier (BBB) disruption, oligodendrocyte precursor cells (OPCs) overexpress proteoglycan nerve/glial antigen 2 (NG2), proliferate, and make contacts with the microvessel wall. To explore whether OPCs may actually be recruited within the neurovascular unit (NVU), de facto intervening in its cellular and molecular composition, we quantified by immunoconfocal morphometry the presence of OPCs in contact with brain microvessels, during postnatal cerebral cortex vascularization at postnatal day 6, in wildtype (WT) and NG2 knock-out (NG2KO) mice, and in the cortex of adult naive and EAE-affected WT and NG2KO mice. As observed in WT mice during postnatal development, a higher number of juxtavascular and perivascular OPCs was revealed in adult WT mice during EAE compared to adult naive WT mice. In EAE-affected mice, OPCs were mostly associated with microvessels that showed altered claudin-5 and occludin tight junction (TJ) staining patterns and barrier leakage. In contrast, EAE-affected NG2KO mice, which did not show any significant increase in vessel-associated OPCs, seemed to retain better preserved TJs and BBB integrity. As expected, absence of NG2, in both OPCs and pericytes, led to a reduced content of vessel basal lamina molecules, laminin, collagen VI, and collagen IV. In addition, analysis of the major ligand/receptor systems known to promote OPC proliferation and migration indicated that vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor-AA (PDGF-AA), and the transforming growth factor-beta (TGF-beta) were the molecules most likely involved in proliferation and recruitment of vascular OPCs during EAE. These results were confirmed by real time-PCR that showed Fgf2, Pdgfa and Tgfb expression on isolated cerebral cortex microvessels and by dual RNAscope-immunohistochemistry/ in situ hybridization (IHC/ISH), which detected Vegfa and Vegfr2 transcripts on cerebral cortex sections. Overall, this study suggests that vascular OPCs, in virtue of their developmental arrangement and response to neuroinflammation and growth factors, could be integrated among the classical NVU cell components. Moreover, the synchronized activation of vascular OPCs and pericytes during both BBB development and dysfunction, points to NG2 as a key regulator of vascular interactions