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11.
Michela Pecoraro Stefania Marzocco Silvia Franceschelli Ada Popolo 《International journal of molecular sciences》2022,23(12)
Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancer cases, causing a more aggressive tumour growth and poor prognosis. Trastuzumab, the humanized antibody targeted to HER2, increased the life expectancy of patients, but severe cardiotoxicity emerged as a long-term adverse effect. Clinical evidence highlights that Trastuzumab-induced cardiotoxicity drastically increases in association with Doxorubicin; however, the exact mechanisms involved remain incompletely understood. In order to analyse the molecular mechanisms involved and the possible adaptative responses to Trastuzumab and Doxorubicin treatment, in this study, H9c2 cardiomyoblasts were used. Results showed that Trastuzumab and Doxorubicin sequential administration in cardiomyoblast increased cytosolic and mitochondrial ROS production, intracellular calcium dysregulation, mitochondrial membrane depolarization, and the consequent apoptosis, induced by both Trastuzumab and Doxorubicin alone. Furthermore, in these conditions, we observed increased levels of Connexin43 phosphorylated on Ser368 (pCx43). Since phosphorylation on Ser368 decreases gap junction intracellular communication, thus reducing the spread of death signals to adjacent cells, we hypothesized that the increase in pCx43 could be an adaptative response implemented by cells to defend neighbouring cells by Trastuzumab and Doxorubicin sequential administration. However, the other side of the coin is the resulting conduction abnormalities. 相似文献
12.
Marika Lanza Alessia Filippone Giovanna Casili Letterio Giuffr Sarah Adriana Scuderi Irene Paterniti Michela Campolo Salvatore Cuzzocrea Emanuela Esposito 《International journal of molecular sciences》2022,23(9)
Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we evaluated the role of the short-chain fatty acids (SCFAs) as sodium propionate (SP) and sodium butyrate (SB) on microbiota profile and intestinal permeability in a mouse model of migraine induced by nitroglycerine (NTG). The mice were orally administered SB and SP at the dose of 10, 30 and 100 mg/kg, 5 min after NTG intraperitoneal injections. Behavioral tests were used to evaluate migraine-like pain. Histological and molecular analyses were performed on the intestine. The composition of the intestinal microbiota was extracted from frozen fecal samples and sequenced with an Illumina MiSeq System. Our results demonstrated that the SP and SB treatments attenuated hyperalgesia and pain following NTG injection. Moreover, SP and SB reduced histological damage in the intestine and restored intestinal permeability and the intestinal microbiota profile. These results provide corroborating evidence that SB and SP exert a protective effect on central sensitization induced by NTG through a modulation of intestinal microbiota, suggesting the potential application of SCFAs as novel supportive therapies for intestinal disfunction associated with migraine. 相似文献
13.
Nowadays two main approaches are being pursued to reduce energy consumption of networks: the use of sleep modes in which devices enter a low-power state during inactivity periods, and the adoption of energy proportional mechanisms where the device architecture is designed to make energy consumption proportional to the actual load. Common to all the proposals is the evaluation of energy saving performance by means of simulation or experimental evidence, which typically consider a limited set of benchmarking scenarios. 相似文献
14.
The ninth edition of the biennial conference series “Nexus: Relationships Between Architecture and Mathematics” took place at the Politecnico di Milan in June 2012. There are many connections between architecture and mathematics: mathematic principles may be used as a basis for an architectural design, or as a tool for analyzing an existing monument; architecture may be a concrete expression of mathematical ideas, becoming, in a sense, “visual mathematics”. The purpose of the Nexus conference series is to bring together all those working with ideas related to both architecture and mathematics, and to allow researchers to exchange ideas first-hand. Papers presented at the conference are published in the Nexus Network Journal, providing a permanent archive of studies in architecture and mathematics, and in 2012 a special volume of papers from the Ph.D. Day and the poster session was published. 相似文献
15.
Rossella Di Guida Angela Casillo Juan M. Toms Susana Merino Maria Michela Corsaro 《International journal of molecular sciences》2022,23(3)
Aeromonas species are found in the aquatic environment, drinking water, bottled mineral water, and different types of foods, such as meat, fish, seafood, or vegetables. Some of these species are primary or opportunistic pathogens for invertebrates and vertebrates, including humans. Among the pathogenic factors associated with these species, there are the lipopolysaccharides (LPSs). LPSs are the major components of the external leaflet of Gram-negative bacterial outer membrane. LPS is a glycoconjugate, generally composed of three portions: lipid A, core oligosaccharide, and O-specific polysaccharide or O-antigen. The latter, which may be present (smooth LPS) or not (rough LPS), is the most exposed part of the LPS and is involved in the pathogenicity by protecting infecting bacteria from serum complement killing and phagocytosis. The O-antigen is a polymer of repeating oligosaccharide units with high structural variability, particularly the terminal sugar, that confers the immunological specificity to the O-antigen. In this study, we established the structure of the O-chain repeating unit of the LPS from Aeromonas bivalvium strain 868 ET (=CECT 7113T = LMG 23376T), a mesophilic bacterium isolated from cockles (Cardium sp.) and obtained from a retail market in Barcelona (Spain), whose biosynthesis core LPS cluster does not contain the waaE gene as most of Aeromonas species. After mild acid hydrolysis, the lipid A was removed by centrifugation and the obtained polysaccharide was fully characterized by chemical analysis and NMR spectroscopy. The polymer consists of a heptasaccharide repeating unit containing D-GalNAc, L-Rha, D-GlcNAc, and D-FucNAc residues. 相似文献
16.
Federico Bolognesi Nicola Fazio Filippo Boriani Viscardo Paolo Fabbri Davide Gravina Francesca Alice Pedrini Nicoletta Zini Michelina Greco Michela Paolucci Maria Carla Re Sofia Asioli Maria Pia Foschini Antonietta DErrico Nicola Baldini Claudio Marchetti 《International journal of molecular sciences》2022,23(3)
Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique. 相似文献
17.
Emanuele Tosi Michela Azzolini Marilinda Lorenzini Sandra Torriani Bruno Fedrizzi Fabio Finato Michela Cipriani Giacomo Zapparoli 《European Food Research and Technology》2013,236(5):853-862
The influence of noble rot on the quality of Recioto di Soave, a “passito” sweet white wine, is greatly variable depending on the occurrence of favourable seasonal conditions for the mould infection. Botrytized wines were produced from grapes inoculated with conidia suspensions to evaluate the effects of noble rot on volatile compounds profile of Recioto di Soave wine. Different development stages of Botrytis cinerea and degree of grape withering were ascertained by must analysis. Several volatile components were involved in marked changes depending on the infection and grape withering level. Fruity esters, carbonyl compounds, phenols, lactones and acetamides greatly changed among botrytized wines. The results demonstrated that the level of B. cinerea infection and the degree of grape withering exert considerable influence on the volatile composition of this sweet wine. Strain-dependent effects were also preliminary ascertained. The process of induction of grape botrytization presented in this study could be recommendable for the industrial production of botrytized Recioto di Soave wine. 相似文献
18.
Dr. Lalit N. Goswami Dr. Tyson J. Olds Dr. Terri G. Monk Dr. Quinn L. Johnson Dr. James P. Dilger Dr. Mohammed A. Shanawaz Dr. Satish S. Jalisatgi Dr. M. Frederick Hawthorne Dr. George R. Kracke 《ChemMedChem》2019,14(11):1108-1114
We synthesized a family of neuromuscular blocking agents (NMB) based on decamethonium, but containing a carborane cluster in the methylene chain between the two quaternary ammonium groups. The carborane cluster isomers o-NMB, m-NMB, and p-NMB were tested in animals for neuromuscular block and compared with agents used clinically: rocuronium and decamethonium. All three isomers caused reversible muscle weakness in mice as determined by grip strength and inverted screen tests, with a potency rank of p-NMB > rocuronium > decamethonium > m-NMB > o-NMB. The mechanism of action of the compounds was determined by using the in vitro rat phrenic nerve hemi-diaphragm preparation and electrophysiologic measurements in cells. Neostigmine reversed hemi-diaphragm weakness caused by the three isomers and rocuronium, but not succinylcholine. In electrophysiologic recordings of currents through acetylcholine receptor channels, the carborane compounds did not activate channel activity but did inhibit channel activation by acetylcholine. These results demonstrate that the carborane neuromuscular blocking agents are non-depolarizers in contrast to the depolarizing action of the parent compound. 相似文献
19.
Volpini R Marucci G Buccioni M Dal Ben D Lambertucci C Lammi C Mishra RC Thomas A Cristalli G 《ChemMedChem》2011,6(6):1074-1080
Guanosine, released extracellularly from neurons and glial cells, plays important roles in the central nervous system, including neuroprotection. The innovative DELFIA Eu‐GTP binding assay was optimized for characterization of the putative guanosine receptor binding site at rat brain membranes by using a series of novel and known guanosine derivatives. These nucleosides were prepared by modifying the purine and sugar moieties of guanosine at the 6‐ and 5′‐positions, respectively. Results of these experiments prove that guanosine, 6‐thioguanosine, and their derivatives activate a G protein‐coupled receptor that is different from the well‐characterized adenosine receptors. 相似文献
20.
Dal Ben D Antonini I Buccioni M Lambertucci C Marucci G Thomas A Volpini R Cristalli G 《ChemMedChem》2011,6(7):1163-1171
Neuropeptide?S (NPS) is a 20-amino acid peptide of great interest due to its possible involvement in several biological processes, including food intake, locomotion, wakefulness, arousal, and anxiety. Structure-activity relationship studies of NPS have identified key points for structural modifications with the goal of modulating NPS receptor (NPSR) agonist activity or achieving antagonism at the same receptor. Only limited information is available for nonpeptide NPSR antagonists. In the last year, several studies have been reported in literature which present various series of small molecules as antagonists of this receptor. The results allow a comparison of the structures and activities of these molecules, leading to the design of new ligands with increased potency and improved pharmacological and pharmacokinetic profiles. This work presents a brief overview of the available information regarding structural features and pharmacological characterization of published nonpeptide NPSR antagonists. 相似文献