Growth and glycemic control in children with type 1 diabetes and asymptomatic celiac disease treated with a gluten -free diet for 1 year

To compare growth and glycemic control in children with type 1 diabetes and silent celiac disease treated with a gluten-free diet for 1 year with those of similar age and gender with type 1 diabetes but without celiac disease, 16 type 1 diabetes patients with silent celiac disease were enrolled and each celiac disease-positive case was matched for age, sex, and duration of diabetes with two type 1 diabetes controls with negative serologic markers of celiac disease. All 16 children with positive celiac disease serology had histologic features consistent with celiac disease despite the absence of symptoms. The mean growth and metabolic control values were similar between children with type 1 diabetes and celiac disease and those with type 1 diabetes but without celiac disease. This study seems to suggest that the early diagnosis of celiac disease and initiation of a gluten-free diet may prevent further deterioration in the nutritional status of children with type 1 diabetes and celiac disease and may reduce the prospect of celiac disease complications without any impact on type 1 diabetes control

First Characterization of Human Amniotic Fluid Stem Cell Extracellular Vesicles as a Powerful Paracrine Tool Endowed with Regenerative Potential

Human amniotic fluid stem cells (hAFS) have shown a distinct secretory profile and significant regenerative potential in several preclinical models of disease. Nevertheless, little is known about the detailed characterization of their secretome. Herein we show for the first time that hAFS actively release extracellular vesicles (EV) endowed with significant paracrine potential and regenerative effect. c-KIT(+) hAFS were isolated from leftover samples of amniotic fluid from prenatal screening and stimulated to enhance EV release (24 hours 20% O2 versus 1% O2 preconditioning). The capacity of the c-KIT(+) hAFS-derived EV (hAFS-EV) to induce proliferation, survival, immunomodulation, and angiogenesis were investigated in vitro and in vivo. The hAFS-EV regenerative potential was also assessed in a model of skeletal muscle atrophy (HSA-Cre, Smn(F7/F7) mice), in which mouse AFS transplantation was previously shown to enhance muscle strength and survival. hAFS secreted EV ranged from 50 up to 1,000 nm in size. In vitro analysis defined their role as biological mediators of regenerative, paracrine effects while their modulatory role in decreasing skeletal muscle inflammation in vivo was shown for the first time. Hypoxic preconditioning significantly induced the enrichment of exosomes endowed with regenerative microRNAs within the hAFS-EV. In conclusion, this is the first study showing that c-KIT(+) hAFS dynamically release EV endowed with remarkable paracrine potential, thus representing an appealing tool for future regenerative therapy. Stem Cells Translational Medicine 2017;6:1340-1355

Epidemiological study of pathogens isolated from blood in Liguria (January-April 2010)

Objectives. An epidemiological study to identify the most represented pathogens isolated from blood and to evaluate their antibiotic susceptibility patterns, was conducted. Methods. Seven clinical microbiology laboratories, homogeneously distributed in the Ligurian area,were required to collected all consecutive non-duplicates strains isolated froom blood cultures during January 2010 to April 2010. The strains were sent to the reference laboratory (Sezione di Microbiologia del DISC, University of Genoa, Italy). Results. A total of 277 microorganisms were enrolled, including 155 Gram positive and 122 Gram negative.The most represented pathogens were: Escherichia coli (68), Staphylococcus aureus (57), Staphylococcus epidermidis (32), Staphylococcus hominis (17), Pseudomonas aeruginosa (15), Klebsiella pneumoniae (15), Enterococcus faecalis (11). Samples were collected mainly from medicine (66, 33.3%, of this number was determined by E. coli), intensive care units (33, 18.2% of this number consisted of S. epidermidis), surgery (24, 33.3% consisted of E. coli) and infectious diseases (20, of which S. aureus, E. coli and S. epidermidis equally represented 20.0%).Among the Staphylococci the most active molecules were: vancomycin and teicoplanin (100% of susceptible strains), chloramphenicol (92.3%) and trimethoprim-sulfamethoxazole (89.8%). Among the OXA-R Staphylococci (81/123, 65.9%) the most active molecules were: vancomycin and teicoplanin (100% of susceptible strains), chloramphenicol (93.8%) and trimethoprim-sulfamethoxazole (84.8%). Enterococci showed rates of resistance to vancomycin of 5.9%. Enterobacteriaceae exhibited resistance to ampicillin (77.5%), trimethoprim-sulfamethoxazole (42.6%), ciprofloxacin (41.2%), ceftriaxone (37.5%), ceftazidime (28.2%), cefepime (26.7%), cefoxitin (22.1%), piperacillintazobactam (20.4%), imipenem (4.7%) and amikacin (2.9%). The Gram negative non-Enterobacteriaceae showed rates of resistance of 100% to ceftriaxone, 81.3% to trimethoprim-sulfamethoxazole, 42.1% to ciprofloxacin and piperacillin-tazobactam, 33.3% to ceftazidime, 31.6% to cefepime, 27.8% to imipenem, 26.3 % to amikacin. Conclusions. The data show a higher incidence of Gram positive (56%) in comparison to Gram negative (44%).This confirms the high incidence of oxacillino-resistance in Staphylococci in our geographic area.Against Enterobacteriaceae rates of resistance were observed in excess of 20% for all drugs tested except imipenem (4.7%) and amikacin (2.9%). The proportion of imipenem-resistant isolates was constituted of strains of K. pneumoniae carbapenemase producers

Anthropometric and glucometabolic changes in an aged mouse model of lipocalin-2 overexpression

Background:: Lipocalin-2 (LCN2) is widely expressed in the organism with pleiotropic roles. In particular, its overexpression correlates with tissue stress conditions including inflammation, metabolic disorders, chronic diseases and cancer. Objectives:: To assess the effects of systemic LCN2 overexpression on adipose tissue and glucose metabolism. Subjects:: Eighteen-month-old transgenic mice with systemic LCN2 overexpression (LCN2-Tg) and age/sex-matched wild-type mice. Methods:: Metabolic cages; histology and real-time PCR analysis; glucose and insulin tolerance tests; ELISA; flow cytometry; microPET and serum analysis. Results:: LCN2-Tg mice were smaller compared to controls but they ate (P = 0.0156) and drank (P = 0.0057) more and displayed a higher amount of visceral adipose tissue. Furthermore, LCN2-Tg mice with body weight 6520 g showed adipocytes with a higher cell area (P < 0.0001) and altered expression of genes involved in adipocyte differentiation and inflammation. In particular, mRNA levels of adipocyte-derived Pparg (P 64 0.0001), Srebf1 (P < 0.0001), Fabp4 (P = 0.056), Tnfa (P = 0.0391), Il6 (P = 0.0198), and Lep (P = 0.0003) were all increased. Furthermore, LCN2-Tg mice displayed a decreased amount of basal serum insulin (P = 0.0122) and a statistically significant impaired glucose tolerance and insulin sensitivity consistent with Slc2a2 mRNA (P 64 0.0001) downregulated expression. On the other hand, Insr mRNA (P 64 0.0001) was upregulated and correlated with microPET analysis that demonstrated a trend in reduced whole-body glucose consumption and MRGlu in the muscles and a significantly reduced MRGlu in brown adipose tissue (P = 0.0247). Nevertheless, an almost nine-fold acceleration of hexokinase activity was observed in the LCN2-Tg mice liver compared to controls (P = 0.0027). Moreover, AST and ALT were increased (P = 0.0421 and P = 0.0403, respectively), which indicated liver involvement also demonstrated by histological staining. Conclusions:: We show that LCN2 profoundly impacts adipose tissue size and function and glucose metabolism, suggesting that LCN2 should be considered as a risk factor in ageing for metabolic disorders leading to obesity

Addition of Conductive Materials to Support Syntrophic Microorganisms in Anaerobic Digestion

Syntrophy and interspecies electron transfer among different microbial groups occurs in anaerobic digestion, and many papers recently reported their positive effect on biogas and methane production. In this paper, we present the results on the effect of conductive material, i.e., graphene, PAC and biochar addition in 3.5 L batch experiments, analyzing the biogas production curve. A peculiar curve pattern occurred in the presence of conductive materials. Compared to the respective controls, the addition of graphene produced a biogas surplus of 33%, PAC 20% and biochar 8%. Microbial community molecular analysis showed that syntrophic microorganisms present in the inoculum were stimulated by the conductive material addition. Graphene also appears to promote an interspecies electron transfer between Geobacter sp. and ca. Methanofastidiosum. This paper contributes to the understanding of the DIET-related microbial community dynamic in the presence of graphene and PAC, which could be exploited to optimize biogas and methane production in real-scale applications

Addition of Conductive Materials to Support Syntrophic Microorganisms in Anaerobic Digestion

Syntrophy and interspecies electron transfer among different microbial groups occurs in anaerobic digestion, and many papers recently reported their positive effect on biogas and methane production. In this paper, we present the results on the effect of conductive material, i.e., graphene, PAC and biochar addition in 3.5 L batch experiments, analyzing the biogas production curve. A peculiar curve pattern occurred in the presence of conductive materials. Compared to the respective controls, the addition of graphene produced a biogas surplus of 33%, PAC 20% and biochar 8%. Microbial community molecular analysis showed that syntrophic microorganisms present in the inoculum were stimulated by the conductive material addition. Graphene also appears to promote an interspecies electron transfer between Geobacter sp. and ca. Methanofastidiosum. This paper contributes to the understanding of the DIET-related microbial community dynamic in the presence of graphene and PAC, which could be exploited to optimize biogas and methane production in real-scale applications

Fenretinide (4-HPR) targets caspase-9, ERK 1/2 and the Wnt3a/\u3b2-catenin pathway in medulloblastoma cells and medulloblastoma cell spheroids

Medulloblastoma (MB), a neuroectodermal tumor arising in the cerebellum, represents the most frequent childhood brain malignancy. Current treatments for MB combine radiation and chemotherapy and are often associated with relevant side effects; novel therapeutic strategies are urgently needed. N-(4-Hydroxyphenyl) retinamide (4-HPR, fenretinide), a synthetic analogue of all-trans retinoic acid, has emerged as a promising and well-tolerated cancer chemopreventive and chemotherapeutic agent for various neoplasms, from breast cancer to neuroblastoma. Here we investigated the effects of 4-HPR on MB cell lines and identified the mechanism of action for a potential use in therapy of MB. Flow cytometry analysis was performed to evaluate 4-HPR induction of apoptosis and oxygen reactive species (ROS) production, as well as cell cycle effects. Functional analysis to determine 4-HPR ability to interfere with MB cell migration and invasion were performed. Western Blot analysis were used to investigate the crucial molecules involved in selected signaling pathways associated with apoptosis (caspase-9 and PARP-1), cell survival (ERK 1/2) and tumor progression (Wnt3a and \u3b2-catenin). We show that 4-HPR induces caspase 9-dependent cell death in DAOY and ONS-76 cells, associated with increased ROS generation, suggesting that free radical intermediates might be directly involved. We observed 4-HPR induction of cell cycle arrest in G1/S phase, inactivated \u3b2-catenin, and inhibition of MB cell migration and invasion. We also evaluated the ability of 4-HPR to target MB cancer-stem/cancer-initiating cells, using an MB spheroids model, followed by flow cytometry and quantitative real-time PCR. 4-HPR treatment reduced DAOY and ONS-76 spheroid formation, in term of number and size. Decreased expression of the surface markers CD133+ and ABCG2+ as well as Oct-4 and Sox-2 gene expression were observed on BTICs treated with 4-HPR further reducing BITIC invasive activities. Finally, we analyzed 4-HPR ability to inhibit MB tumor cell growth in vivo in nude mice. Taken together, our data suggest that 4-HPR targets both parental and MB tumor stem/initiating cell-like populations. Since 4-HPR exerts low toxicity, it could represent a valid compound in the treatment of human MB

Effects of diet-derived molecules on the tumor microenvironment

It is now widely accepted that tumors are a complex tissue composed, in addition to the cancer cells, by endothelial cells and their precursors, stromal cells, pericytes, smooth muscle cells, fibroblasts, myofibroblasts. Inflammatory and immune cells such as macrophages, neutrophils, granulocytes, mast cells, B and T cells, natural killer (NK) and dendritic cells also infiltrate the tumor to constitute the microenvironment. All these players interact with each other and with tumor cells through specific molecular pathways resulting in the production of an intricate network of molecular mediators, cytokines and growth factors providing the proper conditions for tumor maintenance, growth and propagation. Several pathways of cell-cell interactions within the microenvironment have been previously investigated and extensively studied in physiological and pathological scenarios. Some of these pathways can be targeted with therapeutic drugs during tumor progression. However, a more efficacious approach would be to halt tumor-host interactions before a cancer develops or metastasizes. Many phytochemicals and diet derivatives are able to act as chemopreventive agents, targeting the tumor microenvironment and in particular inflammatory angiogenesis, in a new discipline that we named "angioprevention". In this review we analyze some of the potential phytochemical drugs, natural or synthetic, that seem to owe part of their chemopreventive potential to their action on the tumor microenvironment. In particular, we provide an overview of the pathways regulated by chemopreventive microenvironment-active substances: oleanic acid triterpenoids (CDDOs), resveratrol, epigallocathechin gallate (EGCG), xanthohumol and curcumin