2,333 research outputs found

    Design of hybrid gels based on gellan-cholesterol derivative and P90G liposomes for drug depot applications

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    Gels are extensively studied in the drug delivery field because of their potential benefits in therapeutics. Depot gel systems fall in this area, and the interest in their development has been focused on long-lasting, biocompatible, and resorbable delivery devices. The present work describes a new class of hybrid gels that stem from the interaction between liposomes based on P90G phospholipid and the cholesterol derivative of the polysaccharide gellan. The mechanical properties of these gels and the delivery profiles of the anti-inflammatory model drug diclofenac embedded in such systems confirmed the suitability of these hybrid gels as a good candidate for drug depot applications

    Synthesis of a novel ester of hydroxytyrosol and lipoic acid exhibiting an antiproliferative effect on human colon cancer HT-29 cells

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    A novel hydroxytyrosol-lipoic acid derivative has been synthesized. Key steps are an esterification reaction between tyrosol and cJipoic acid derivatives and a regioselective aromatic hydroxylation ofthe monohydroxylated ester performed by 2-iodoxybenzoic acid (IBX) followed by an in situ reductionw ith sodium dithionite (Na2S2O4T).h e novel estere xhibited an antiproliferative effect on the human colorectal adenocarcinoma HT-29 cell line signifrcantly more potent than its parent compounds

    Metrology for marine monitoring: cooperation between INRiM and ENEA

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    The study of the status of the marine environment is typically carried out by monitoring several parameters, both chemical and physicochemical, classified as Essential Ocean Variables by the Global Climate Observing System. These variables are useful to obtain quantifiable indications to monitor the phenomena occurring in the oceans and to relate them to the changes occurring on the global scale in all the environmental compartments. In this framework, a research collaboration is ongoing between the Italian National Metrology Institute (INRiM) and the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), to support the collection, validation and maintenance of reliable and accurate databases, by applying the concepts of metrology from the laboratory to the field. Among the main Essential Ocean Variables, the dissolved oxygen and the partial pressure of carbon dioxide are key parameters to monitor the changing ocean and are largely measured in stations around the globe. INRiM and ENEA are collaborating in the measurement of these variables, focusing on the metrological traceability issues and the measurement uncertainty evaluation, also exploiting innovative Internet of Underwater Things (IoUT) in situ monitoring systems developed by WSense, spinoff of Sapienza University

    Association between proton-pump inhibitors (PPI) and metronomic capecitabine (MCAP) as salvage treatment for patients with advanced gastro-intestinal tumoursa. A randomized phase II study

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    Background: Several researches have shown that acidification of tumor microenvironment is the basis for tumor invasiveness, ability to metastasize S382 Abstracts and cytotoxic agents resistance; therefore proton pump inhibitors (PPI) could significantly increase the chemosensitivity. In our retrospective work we have investigated the role of capecitabine (mCAP) at metronomic dosage of 1500 mg/die as salvage chemotherapy in patients with metastatic colorectal cancer, showing a moderately activity and well tolerability. In this prospective study we evaluated safety and activity of mCAP in the advanced gastro-intestinal patients and the putative chemosensitizing activity of a specific PPI (Rabeprazole) in association to this therap

    Role of D(-)-Lactic Acid in Prevention of Chlamydia trachomatis Infection in an In Vitro Model of HeLa Cells

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    A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(-)-lactic acid isomer are known to exert stronger protection. However, the molecular mechanisms underlying this antimicrobial action are not well understood. The aim of this study was to investigate the role of D(-)-lactic acid isomer in the prevention of C. trachomatis infection in an in vitro HeLa cell model. We selected two strains of lactobacilli belonging to different species: a vaginal isolate of Lactobacillus crispatus that releases both D(-) and L(+) isomers and a strain of Lactobacillus reuteri that produces only the L(+) isomer. Initially, we demonstrated that L. crispatus was significantly more effective than L. reuteri in reducing C. trachomatis infectivity. A different pattern of histone acetylation and lactylation was observed when HeLa cells were pretreated for 24 h with supernatants of Lactobacillus crispatus or L. reuteri, resulting in different transcription of genes such as CCND1, CDKN1A, ITAG5 and HER-1. Similarly, distinct transcription patterns were found in HeLa cells treated with 10 mM D(-)- or L(+)-lactic acid isomers. Our findings suggest that D(-) lactic acid significantly affects two non-exclusive mechanisms involved in C. trachomatis infection: regulation of the cell cycle and expression of EGFR and α5β1-integrin

    What’s in the bee nest holes? A single aggregation of Megachile parietina reveals and helps to fill up Eltonian shortfalls

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    Megachile (Chalicodoma) parietina (Geoffroy, 1785) is a Palearctic solitary bee included in the Red List of some central European Countries. Females build durable nests, reused year after year, by mixing soil with a salivary secretion. Like for most solitary bees, the resources contained within M. parietina nests attract several other insects which exploit pollen supplies or feed on the immature brood. These associated insects have mainly been studied for mantained bees and considered for their effect on the host reproductive success.A very large nesting aggregation of M. parietina in Central Tuscany has been studied for three consecutive years. We have identified 32 associated insect species, which certainly are an underestimate of the species present. Among the identified species, only eight had been previously reported for M. parietina. All the species were classified both according to the specificity for the host taxon (Chalicodoma, Megachilidae, Anthophila, Hymenoptera, Others) and to the ecological relationship (cleptoparasites, parasitoids, predators of larvae, food commensal, scavengers, and occasional nest users).This highlighted both the richness of the ecological network within the nesting aggregation and the value of studying these nesting sites to fill Eltonian shortfalls, i.e. the deficiency in ecology knowledge, of bees and their associated fauna.Implications for insect conservation.We suggest that, besides their role in pollination, large and stable bee nesting sites increase the local insect biodiversity, and that attention should be paid to their conservation within actions aimed to support populations of wild pollinators

    Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer

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    Familial aggregation is a significant risk factor for the development of thyroid cancer and Familial Non-Medullary Thyroid Cancer (FNMTC) accounts for 5-7% of all NMTC. Whole Exome Sequencing analysis in the family affected by FNMTC with oncocytic features where our group previously identified a predisposing locus on chromosome 19p13.2, revealed a novel heterozygous mutation (c.400G>A, NM_012335; p.Gly134Ser) in exon 5 of MYO1F, mapping to the linkage locus. In the thyroid FRTL-5 cell model stably expressing the mutant MYO1F p.Gly134Ser protein we observed an altered mitochondrial network, with increased mitochondrial mass and a significant increase of both intracellular and extracellular Reactive Oxygen Species, compared to cells expressing the wild-type protein or carrying the empty vector. The mutation conferred a significant advantage in colony formation, invasion and anchorage independent growth. These data were corroborated by in vivo studies in zebrafish, since we demonstrated that the mutant MYO1F p.Gly134Ser, when overexpressed, can induce proliferation in whole vertebrate embryos, compared to the wild-type one. MYO1F screening in additional 192 FNMTC families identified another variant in exon 7, which leads to exon skipping, and is predicted to alter the ATP-binding domain in MYO1F. Our study identified for the first time a role for MYO1F in NMTC. This article is protected by copyright. All rights reserved

    Vonoprazan for treatment of gastroesophageal reflux: pharmacodynamic and pharmacokinetic considerations

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    This review provides an update on the pharmacokinetic properties of vonoprazan and their correlates with pharmacodynamics; preliminary data on the therapeutic efficacy of vonoprazan as compared to lansoprazole in GERD patients Expert opinion: At variance from all available PPIs, vonoprazan acts directly on H+,K+-ATPase irrespectively of its activity, providing a fast onset of action without requiring acid activation and specific administration timing. Clinical and pharmacological investigations have confirmed a more rapid, potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability, as compared with PPIs. Preliminary data in patients with erosive esophagitis (EE) have shown the non-inferiority of vonoprazan to lansoprazole in terms of symptom relief and healing rate. Since these pharmacokinetic advantages, it is expected that it will have a significant favorable impact on GERD management. However, the clinical use of vonoprazan raises also some issues about its efficacy and safety in the long-term that deserve verification and careful investigation
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