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31.
Ahmed Abd El-Fattah Elizabeth Grillo Fernandes Federica Chiellini Emo Chiellini 《International journal of molecular sciences》2022,23(3)
Amphiphilic copolymers are appealing materials because of their interesting architecture and tunable properties. In view of their application in the biomedical field, the preparation of these materials should avoid the use of toxic compounds as catalysts. Therefore, enzymatic catalysis is a suitable alternative to common synthetic routes. Pentablock copolymers (CUC) were synthesized with high yields by ring-opening polymerization of ε-caprolactone (ε-CL) initiated by Pluronic (EPE) and catalyzed by Candida antarctica lipase B enzyme. The variables to study the structure–property relationship were EPEs’ molecular weight and molar ratios between ε-CL monomer and EPE macro-initiator (M/In). The obtained copolymers were chemically characterized, the molecular weight determined, and morphologies evaluated. The results suggest an interaction between the reaction time and M/In variables. There was a correlation between the differential scanning calorimetry data with those of X-ray diffraction (WAXD). The length of the central block of CUC copolymers may have an important role in the crystal formation. WAXD analyses indicated that a micro-phase separation takes place in all the prepared copolymers. Preliminary cytotoxicity experiments on the extracts of the polymer confirmed that these materials are nontoxic. 相似文献
32.
Barbara Eleni Rosato Roberta Marra Vanessa DOnofrio Federica Del Giudice Simone Della Monica Achille Iolascon Immacolata Andolfo Roberta Russo 《International journal of molecular sciences》2022,23(3)
Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells. 相似文献
33.
Giulia Fiscon Federica Conte Lorenzo Farina Paola Paci 《International journal of molecular sciences》2022,23(7)
Drug repurposing strategy, proposing a therapeutic switching of already approved drugs with known medical indications to new therapeutic purposes, has been considered as an efficient approach to unveil novel drug candidates with new pharmacological activities, significantly reducing the cost and shortening the time of de novo drug discovery. Meaningful computational approaches for drug repurposing exploit the principles of the emerging field of Network Medicine, according to which human diseases can be interpreted as local perturbations of the human interactome network, where the molecular determinants of each disease (disease genes) are not randomly scattered, but co-localized in highly interconnected subnetworks (disease modules), whose perturbation is linked to the pathophenotype manifestation. By interpreting drug effects as local perturbations of the interactome, for a drug to be on-target effective against a specific disease or to cause off-target adverse effects, its targets should be in the nearby of disease-associated genes. Here, we used the network-based proximity measure to compute the distance between the drug module and the disease module in the human interactome by exploiting five different metrics (minimum, maximum, mean, median, mode), with the aim to compare different frameworks for highlighting putative repurposable drugs to treat complex human diseases, including malignant breast and prostate neoplasms, schizophrenia, and liver cirrhosis. Whilst the standard metric (that is the minimum) for the network-based proximity remained a valid tool for efficiently screening off-label drugs, we observed that the other implemented metrics specifically predicted further interesting drug candidates worthy of investigation for yielding a potentially significant clinical benefit. 相似文献
34.
Luca Maria Chiesa Maria Nobile Federica Ceriani Francesco Arioli 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2018,35(7):1340-1355
Demand for honey is increasing, especially if it is organic and if its nutritional properties are linked to untreated environments in order to guarantee quality for health. Sources of contamination of honey can be divided into environmental and apicultural. Therefore, the distribution of persistent organic pollutants, pesticides and antibiotic residues from geographical areas with different contamination sources (high anthropic impact, intensive farming, husbandry and low anthropic impact) was investigated in order to confirm the potential transfer of xenobiotics into the supply chain and to give beekeepers tools for the selection of areas dedicated to organic production. The presence of polychlorinated biphenyls, polybrominated diphenyl ether and polycyclic aromatic hydrocarbons was confirmed, not only in proximity to highly urbanised centres, where the concentrations were higher, but in all environment contexts, confirming their ubiquity. No antibiotics or neonicotinoids were detected in 95 organic honeys, demonstrating the absence of apicultural treatments and consequently the good quality of honey of different areas. These results are important due to the undefined regulatory European situation on honey antibiotic limits. 相似文献
35.
Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands
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Dr. Silvia Pace Dr. Giandomenico Brogin Dr. Maria Antonietta Stasi Dr. Teresa Riccioni Franco Borsini Dr. Francesca Capocasa Dr. Francesco Manera Carlo Tallarico Dr. Pietro Grossi Dr. Federica Vacondio Dr. Michele Bassi Dr. Francesca Bartoccini Dr. Simone Lucarini Dr. Giovanni Piersanti Prof. Giorgio Tarzia Walter Cabri Dr. Patrizia Minetti 《ChemMedChem》2015,10(7):1149-1152
Inhibition of adenosine A2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A2AR (Ki=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours). 相似文献
36.
Francesca Bugli Federica Massaro Francesco Buonocore Paolo Roberto Saraceni Stefano Borocci Francesca Ceccacci Cecilia Bombelli Maura Di Vito Rosalba Marchitiello Melinda Mariotti Riccardo Torelli Maurizio Sanguinetti Fernando Porcelli 《International journal of molecular sciences》2022,23(4)
The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens. 相似文献
37.
Erica Costantini Lisa Aielli Federica Serra Lorenzo De Dominicis Katia Falasca Pamela Di Giovanni Marcella Reale 《International journal of molecular sciences》2022,23(4)
Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive faster healing, evaluating the keratinocytes migration, cytokines, and matrix metalloproteinases (MMPs) expression. The results showed that RF-EMF treatment promotes keratinocytes’ migration and regulates the expression of genes involved in healing, such as MMPs, tissue inhibitors of metalloproteinases, and pro/anti-inflammatory cytokines, to improve WH. 相似文献
38.
Diana Valeria Rossetti Ilaria Inserra Alessia Nestic Federica Vincenzoni Federica Iavarone Irene Messana Massimo Castagnola Luca Massimi Gianpiero Tamburrini Massimo Caldarelli Claudia Desiderio 《International journal of molecular sciences》2022,23(6)
The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization. 相似文献
39.
The Rovereto Emotion and Cooperation Corpus (RECC) is a new resource collected to investigate the relationship between cooperation
and emotions in an interactive setting. Previous attempts at collecting corpora to study emotions have shown that this data
are often quite difficult to classify and analyse, and coding schemes to analyse emotions are often found not to be reliable.
We collected a corpus of task-oriented (MapTask-style) dialogues in Italian, in which the segments of emotional interest are
identified using psycho-physiological indexes (Heart Rate and Galvanic Skin Conductance) which are highly reliable. We then
annotated these segments in accordance with novel multimodal annotation schemes for cooperation (in terms of effort) and facial
expressions (an indicator of emotional state). High agreement was obtained among coders on all the features. The RECC corpus
is to our knowledge the first resource with psycho-physiological data aligned with verbal and nonverbal behaviour data. 相似文献
40.