Modeling Lung Carcinoids with Zebrafish Tumor Xenograft

Lung carcinoids are neuroendocrine tumors that comprise well-differentiated typical (TCs) and atypical carcinoids (ACs). Preclinical models are indispensable for cancer drug screening since current therapies for advanced carcinoids are not curative. We aimed to develop a novel in vivo model of lung carcinoids based on the xenograft of lung TC (NCI-H835, UMC-11, and NCI-H727) and AC (NCI-H720) cell lines and patient-derived cell cultures in Tg(fli1a:EGFP)^y1 zebrafish embryos. We exploited this platform to test the anti-tumor activity of sulfatinib. The tumorigenic potential of TC and AC implanted cells was evaluated by the quantification of tumor-induced angiogenesis and tumor cell migration as early as 24 h post-injection (hpi). The characterization of tumor-induced angiogenesis was performed in vivo and in real time, coupling the tumor xenograft with selective plane illumination microscopy on implanted zebrafish embryos. TC-implanted cells displayed a higher pro-angiogenic potential compared to AC cells, which inversely showed a relevant migratory behavior within 48 hpi. Sulfatinib inhibited tumor-induced angiogenesis, without affecting tumor cell spread in both TC and AC implanted embryos. In conclusion, zebrafish embryos implanted with TC and AC cells faithfully recapitulate the tumor behavior of human lung carcinoids and appear to be a promising platform for drug screening.     

A Novel Morphological Parameter Predicting Fibrotic Evolution in Myeloproliferative Neoplasms: New Evidence and Molecular Insights

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions; still, a subset of cases shows a rapid evolution towards myelofibrotic bone marrow failure. Specific abnormalities in the megakaryocyte lineage seem to play a central role in this evolution, especially in the bone marrow fibrosis but also in the induction of myeloproliferation. In this review, we analyze the current knowledge of prognostic factors of MPNs related to their evolution to myelofibrotic bone marrow failure. Moreover, we focused the role of the megakaryocytic lineage in the various stages of MPNs, with updated examples of MPNs in vitro and in vivo models and new therapeutic implications.     

Glioblastoma Stem Cells—Useful Tools in the Battle against Cancer

Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy-resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. This review provides an overview of the molecular features, microenvironment, detection, and targeting strategies of GSCs, an essential information required for an efficient therapy. Despite the outstanding results in oncology, researchers are still developing novel strategies, of which one could be targeting the GSCs present in the hypoxic regions and invasive edge of the glioblastoma.     

Radio planning of energy-aware cellular networks

This paper introduces a joint planning and management optimization approach for cellular networks to limit energy consumption while guaranteeing QoS and minimizing operators Capex and Opex. The modeling framework shows that an effective energy-efficient operation depends on the planning decisions. Conversely, it also shows that planning with energy management operation in view yields more versatile topologies than more traditional models based only on Capex. Results for LTE networks are provided and show that savings up to 65% in energy expenses are possible with slight increases in capital investments.     

Effect of Processing on the Physico-Chemical Characteristics of Quinoa Flour (Chenopodium quinoa,Willd)

The nature and extent of the modification of starch in quinoa, caused by various processes like cooking and autoclaving of the seeds, drum drying of the flour and extrusion of the grits was investigated by measuring the physico-chemical properties - the water absorption, water solubility, swelling power, viscosity and degree of gelatinisation - of the processed samples. Autoclaved samples showed the lowest degree of gelatinisation (32.5% by DSC) of the starch, while the degree of gelatinisation of the precooked/drum dried samples was found to be 97.4% by DSC method. Higher polymer degradation was observed in cooked samples than in autoclaved samples as seen in the gel chromatographic separation. The water solubility in cooked samples (5.44 to 15.58) and in autoclaved samples (7.02 to 9.64) increased with the process time. In the extrusion process, the moisture content as well as the compression ratio was found to affect the degree of starch modification significantly (p <0.01).     

Thermal and flammability properties influenced by Zn/Al,Co/Al,and Ni/Al layered double hydroxide in low-density polyethylene nanocomposites

Layered double hydroxide (LDH) containing different metal constituents (Zn, Co, and Ni) was intercalated with different organic anions and has been used as fillers in low-density polyethylene (LDPE), and its thermal and flammability behavior was evaluated. The best thermal stability (∆T_0.5 = 21 °C) was obtained with the LDPE-Ni/Al-dodecyl sulfate (4 wt %) nanocomposite. Addition of hydrophobic LDHs systematically decreases the enthalpy of melting and crystallization compared to the neat polymer. In LDPE-Co/Al-dodecyl sulfate (2 wt %) nanocomposite, the melting and crystallization enthalpies declined by about 45 J/g, indicating a good interaction of the filler with the polymer matrix. A reduction of 20% of the flammability for the LDPE-Ni/Al-stearate (4 wt %) nanocomposite was obtained. On the other hand, Zn–Co LDH as filler in LDPE nanocomposite did not affect effectively the same property. In an innovative study, results indicate that different metal constituents and interlayer anion of LDH as filler can change thermal and flammability properties of the polymer nanocomposite. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48737.     

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT₁ receptors and NADPH oxidase, and lower expression of AT₂, Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.