Cortisol regulates the paracrine action of macrophages by inducing vasoactive gene expression in endometrial cells

The human endometrium undergoes inflammation and tissue repair during menstruation. We hypothesized that the local availability of bioactive glucocorticoids plays an important role in immune cell–vascular cell interactions in endometrium during tissue repair at menstruation, acting either directly or indirectly via tissue resident macrophages. We sought to determine whether endometrial macrophages are direct targets for glucocorticoids; whether cortisol-treated macrophages have a paracrine effect on angiogenic gene expression by endometrial endothelial cells; and whether endometrial macrophages express angiogenic factors. Human endometrium (n = 41) was collected with ethical approval and subject consent. Donor peripheral blood monocyte-derived macrophages were treated with estradiol, progesterone, or cortisol. The effect of peripheral blood monocyte-derived macrophage secretory products on the expression of angiogenic RNAs by endothelial cells was examined. Immunofluorescence was used to examine localization in macrophages and other endometrial cell types across the menstrual cycle. Endometrial macrophages express the glucocorticoid receptor. In vitro culture with supernatants from cortisol-treated peripheral blood monocyte-derived macrophages resulted in altered endometrial endothelial cell expression of the angiogenic genes, CXCL2, CXCL8, CTGF, and VEGFC. These data highlight the importance of local cortisol in regulating paracrine actions of macrophages in the endometrium. CXCL2 and CXCL8 were detected in endometrial macrophages in situ. The expression of these factors was highest in the endometrium during the menstrual phase, consistent with these factors having a role in endometrial repair. Our data have indicated that activation of macrophages with glucocorticoids might have paracrine effects by increasing angiogenic factor expression by endometrial endothelial cells. This might reflect possible roles for macrophages in endometrial repair of the vascular bed after menstruation

Experimental investigations on stored product insect infestation of grains and seeds recently introduced into the Italian market

The growing demand for healthy foods has recently brought new kinds of products to the Italian market to meet consumers’ needs. Currently, quinoa, teff and hemp seeds can be found quite commonly in most stores, as whole or broken grains or flour. These products can be susceptible to pest attacks in different stages of the production process: from storage as whole seeds through the transformation phases to the final products ready for consumption. The aim of this work is to verify susceptibility to infestations, even if only temporary, for these recently introduced products, by two of northern Italy’s most common stored product pests, known for their high polyphagy: Tenebrio molitor L. (Coleoptera: Tenebrionidae) and Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae). Artificial infestation assays were carried out to evaluate the mating and development possibilities for such pests on these grains. The growth rate of larvae, life cycle length and number of individuals which reached the adult stage were also assessed. Insects were obtained from colonies maintained under constant conditions in a climatic chamber (23 ± 1 °C and 65 ± 5% R.H.) at the Di.Pro.Ve.S. laboratory. These environmental conditions were maintained throughout all the assays. Insect colonies were fed on commercially available grains. Significant differences as regards the bionomical traits investigated under the above climatic conditions were observed for each species and the different grain

Insect pest susceptibility of grains and seeds recently introduced to the Italian market: An experimental evaluation

To assess the susceptibility of pseudocereals (amaranth and quinoa), minor cereals (teff and millet), and oilseeds (chia and hemp), now commercially available on the European market, to attacks by polyphagous and cosmopolitan insect pests, laboratory tests were set up. Tests involving controlled infestation of seeds, using laboratory-bred insects (Tenebrio molitor, Tribolium confusum, Oryzaephilus surinamensis, Cryptolestes pusillus and Plodia interpunctella), were carried out in a climatic chamber at 23\ub12 \ub0C and 65\ub15% R.H.. Development time, the number of adults and the weight of these adults were evaluated. The results show that each considered foodstuff has a different susceptibility to infestation and differences both in the number of adults emerged and in their weight compared to control. Millet was the only product that allowed larval development up to the adult stage for all the species examined. No species developed on amaranth. T. confusum and O. surinamensis reached the adult stage on the greatest number of products, 5 and 4 respectively; C. pusillus and T. molitor completed their life cycles on only two commodities: millet and teff, while P. interpunctella only on millet and hemp seeds. Considering the impact of the different pests on the studied grains, T. confusum was the only species able to develop on all the grains, but the number of emerged adults was lower than on the standard diet. These results show that, even if these commodities are new in the European market, they are susceptible to the infestation of common stored product pests that could led to a removal from the market of a contaminated stock, so a continuous monitoring is needed

Preliminary observations on the susceptibility of pseudo-cereals and other new grains for the European market to the attack of stored product beetles

Until a few years ago, pseudo-cereals and some other plants (originating either from Latin America or from Asia or Africa) of interest as food were almost unknown in Europe, but recently they have attracted the attention of researchers because of their growing diffusion in the agri-food industry. In the human diet, pseudo-cereals such as quinoa (Chenopodium quinoa Willdenow), amaranth (Amaranthus spp.) and buckwheat (Fagopyrum esculentum Moench) are appreciated for some properties including high nutritional values; similarly chia (Salvia hispanica L.), which is an oily seed, and teff (Eragrostis tef (Zuccagni) Trotter), which is instead a cereal, have interesting nutritional profiles. The grains of these plants can be consumed in the place of traditional cereals, as such or transformed into flour to obtain bread, pasta or other derivatives. Their cultivation is increasing in various countries of Europe, including Italy and, as for all (other) cereals, they are susceptible to attack by pests after harvest. This aspect cannot be ignored. Our laboratory research has investigated the susceptibility of pseudocereals, chia and teff to attack by some common stored-product beetles and moths known for their more or less marked polyphagy: Rhyzopertha dominica (F.) (Bostrichidae), Sitophilus granarius (L.) (Dryophthoridae), Tenebrio molitor (L.) (Tenebrionidae) and Plodia interpunctella (H\ufcbner) (Pyralidae). Results revealed significant differences in the timescale and means of infestation and larval development: S. granarius and R. dominica grew only on buckwheat; P. interpunctella grew on all seeds except amaranth, with high larval trophic activity, but most larvae died between 60 and 90 days after the beginning of the infestation. T. molitor larval activity was observed on all the grains and the life cycle was not interrupted. This study, still underway, is a first step towards optimizing the storage methods of these new products and to understanding their main risks of infestation and ntamination

Pyrethroid resistance in Italian populations of the mite Varroa destructor: a focus on the Lombardia region

Varroa destructor is one of the major pests against honey bees. Beekeepers can rely on different approaches to try and prevent colony collapses, and the most relevant are acaricide treatments. Pyrethroid resistance was first reported in Lombardia in 1991 and is now spread worldwide. Recently, three different mutations (L925V/I/M) occurring in the voltage-gated sodium channel have been associated with tau-fluvalinate resistance. Furthermore, indirect evidence from laboratory bioassays indicated that high levels of esterases may be involved in mites resistant to tau-fluvalinate. This study provides an update of the actual spread of target-site resistance to tau-fluvalinate in varroa samples collected in the Lombardia region. TaqMan assays showed that mutation L925V is present in this area, however only low frequencies of this resistant allele were detected. The majority of resistant mites were found in the homozygous form (11%), and only a small fraction possessed the heterozygous genotype (2%). Additionally, a protocol was set up to detect esterase activity directly in single mites to determine if metabolic resistance can occur. We observed slight variability among different populations, and piperonyl butoxide showed only very low inhibition of this activity in vitro. Additional evaluation of monooxygenases activity must also be explored in the future

enhanced sparcl1 expression in cancer stem cells improves preclinical modeling of glioblastoma by promoting both tumor infiltration and angiogenesis

Abstract Glioblastoma (GBM) is the most malignant brain tumor of adults and is characterized by extensive cell dissemination within the brain parenchyma and enhanced angiogenesis. Effective preclinical modeling of these key features suffers from several shortcomings. Aim of this study was to determine whether modulating the expression of extracellular matrix (ECM) modifiers in proneural (PN) and mesenchymal (MES) cancer stem cells (CSCs) and in conventional glioma cell lines (GCLs) might improve tumor invasion and vascularization. To this end, we selected secreted, acidic and rich in cysteine-like 1 (SPARCL1) as a potential mediator of ECM remodeling in GBM. SPARCL1 transcript and protein expression was assessed in PN and MES CSCs as well as GCLs, in their xenografts and in patient-derived specimens by qPCR, WB and IHC. SPARCL1 expression was then enforced in both CSCs and GCLs by lentiviral-based transduction. The effect of SPARCL1 gain-of-function on microvascular proliferation, microglia activation and advanced imaging features was tested in intracranial xenografts by IHC and MRI and validated by chorioallantoic membrane (CAM) assays. SPARCL1 expression significantly enhanced the infiltrative and neoangiogenic features of PN and MES CSC/GCL-induced tumors, with the concomitant activation of inflammatory responses associated with the tumor microenvironment, thus resulting in experimental GBMs that reproduced both the parenchymal infiltration and the increased microvascular density, typical of GBM. Overall, these results indicate that SPARCL1 overexpression might be instrumental for the generation of CSC-derived preclinical models of GBM in which the main pathognomonic hallmarks of GBMs are retrievable, making them suitable for effective preclinical testing of therapeutics

Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients

Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency