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排序方式: 共有536条查询结果,搜索用时 16 毫秒
41.
Dr. Francesca Ferlenghi Dr. Michele Mari Prof. Gabriella Gobbi Dr. Gian Marco Elisi Prof. Marco Mor Prof. Silvia Rivara Prof. Federica Vacondio Dr. Silvia Bartolucci Prof. Annalida Bedini Dr. Fabiola Fanini Prof. Gilberto Spadoni 《ChemMedChem》2021,16(19):3071-3082
The MT2-selective melatonin receptor ligand UCM765 (N-(2-((3-methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT1 and MT2 binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with a N-methyl-N-phenyl-amino one led to highly soluble compounds with good microsomal stability and receptor binding affinity. Docking studies into the receptor crystal structure provided a rationale for their binding affinity. Pharmacokinetic characterization in rats highlighted higher plasma concentrations for the N-methyl-N-phenyl-amino derivative, consistent with its improved microsomal stability and makes this compound worthy of consideration for further pharmacological investigation. 相似文献
42.
Bokyung Kim Young Ho Ko Massimiliano Runfola Simona Rapposelli Gabriella Ortore Grazia Chiellini Jin Hae Kim 《International journal of molecular sciences》2021,22(7)
Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases. 相似文献
43.
Domestication is a process of selection driven by humans, transforming wild progenitors into domesticated crops. The grapevine (Vitis vinifera L.), besides being one of the most extensively cultivated fruit trees in the world, is also a fascinating subject for evolutionary studies. The domestication process started in the Near East and the varieties obtained were successively spread and cultivated in different areas. Whether the domestication occurred only once, or whether successive domestication events occurred independently, is a highly debated mystery. Moreover, introgression events, breeding and intense trade in the Mediterranean basin have followed, in the last thousands of years, obfuscating the genetic relationships. Although a succession of studies has been carried out to explore grapevine origin and different evolution models are proposed, an overview of the topic remains pending. We review here the findings obtained in the main phylogenetic and genomic studies proposed in the last two decades, to clarify the fundamental questions regarding where, when and how many times grapevine domestication took place. Finally, we argue that the realization of the pan-genome of grapes could be a useful resource to discover and track the changes which have occurred in the genomes and to improve our understanding about the domestication. 相似文献
44.
A young red wine was aged in containers with different oxygen permeability, i.e. glass, polyethyleneterephtalate (PET) and
polyethyleneterephtalate including an oxygen scavenger (PETA), to determine variations in antioxidant components and antioxidant
activity, determined as radical scavenging activity. The phenolic composition and the antioxidant activity of the wine were
evaluated during approximately 24 weeks of storage at 20 or 30 °C. Significant changes were observed in total anthocyanin
concentration in all samples, while other indexes such as total phenolics and total flavonoids remained stable during storage
in all conditions. The antioxidant activity diminished in all samples, with differences between the various containers, both
at 20 and 30 °C. HPLC analysis showed that important changes occurred in some flavonoid components (catechin, epicatechin,
procyanidin TB2) and in most anthocyanidins in all storage conditions, with greater degradation at 30 °C and in PET bottles.
Samples stored in PETA bottles showed the highest stability. The research demonstrated that ageing-related changes during
storage are influenced by the oxygen permeability of the containers and can be slowed by the use of PET materials with enhanced
oxygen barrier capacity. 相似文献
45.
Domenico Mirri Gaetano Pasini Fabio Filicori Gaetano Iuculano Gabriella Pellegrini 《Measurement》1999,25(4):265
A new model has been proposed for the characterisation of the non-linear dynamic effects of a S/H-ADC device and a new mathematical approach has been introduced to describe its non-ideal dynamic behaviour. The measurement procedure to deduce the parameters of the proposed model is given together with the experimental results on a commercial device. 相似文献
46.
Carlo Ricciardi Giancarlo Canavese Riccardo Castagna Gabriella Digregorio Ivan Ferrante Simone L. Marasso Alessandro Ricci Valentina Alessandria Kalliopi Rantsiou Luca S. Cocolin 《Food and Bioprocess Technology》2010,3(6):956-960
The micro- and nano-technologies coupled with a deep knowledge of organic/inorganic interfaces guarantee an exceptional sensitivity
and specificity of the sensor, while the lab-on-a-chip platform reduces assay times and limits sampling and/or sample preparation,
providing compact and portable objects. Therefore, the development of innovative biosensors such as antibody-immobilized microcantilevers
can overcome the evident limits of nowadays technologies, such as time consuming, expensiveness, difficult automation, low
sensitivity, accuracy, and precision for quantitative methods. The present study proposes two device designs for the detection
of food pathogens, exploiting an antibody-immobilized microcantilever biosensors, a novel class of mass detectors. For the
first one, we integrated the mechanical sensors on a microfluidic platform (lab-on-a-chip) to perform online analysis, directly
in liquid environment. We showed that our portable biosensors could easily detect the presence of pathogenic bacteria such
as Salmonella enterica serotype enteritidis in concentration 105 cfu/mL in just 40 min, without any enrichment and/or sample preparation. To increase the mass sensitivity of our analysis,
we also fabricated microstructures optimized for vibrating in vacuum environment. Using a dip-and-dry technique, we showed
that, in such configuration, the experimental limit of detection is as low as 103 cfu/mL. Due to the extremely small volumes needed, our biosensors operating in vacuum have the potentiality of detecting
the presence or absence of a single cell. 相似文献
47.
48.
Lucia Marseglia Sara Manti Gabriella D’Angelo Antonio Nicotera Eleonora Parisi Gabriella Di Rosa Eloisa Gitto Teresa Arrigo 《International journal of molecular sciences》2015,16(1):378-400
Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases. 相似文献
49.
Patrizia Ferroni Raffaele Palmirotta Gabriella Egeo Cinzia Aurilia Maria Giovanna Valente Antonella Spila Alberto Pierallini Piero Barbanti Fiorella Guadagni 《International journal of molecular sciences》2022,23(22)
White matter hyperintensities (WMHs) in migraine could be related to inflammatory and antioxidant events. The aim of this study is to verify whether migraine patients with WMHs carry a genetic pro-inflammatory/pro-oxidative status. To test this hypothesis, we analyzed lymphotoxin alpha (LTA; rs2071590T and rs2844482G) and superoxide dismutase 1 (SOD1; rs2234694C) and 2 (SOD2; rs4880T) gene polymorphisms (SNPs) in 370 consecutive patients affected by episodic (EM; n = 251) and chronic (CM; n = 119) migraine and in unrelated healthy controls (n = 100). Brain magnetic resonance was available in 183/370 patients. The results obtained show that genotypes and allele frequencies for all tested SNPs did not differ between patients and controls. No association was found between single SNPs or haplotypes and sex, migraine type, cardiovascular risk factors or disorders. Conversely, the LTA rs2071590T (OR = 2.2) and the SOD1 rs2234694C (OR = 4.9) alleles were both associated with WMHs. A four-loci haplotype (TGCT haplotype: rs2071590T/rs2844482G/rs2234694C/rs4880T) was significantly more frequent in migraineurs with WMHs (7 of 38) compared to those without WMHs (4 of 134; OR = 8.7). We may, therefore, conclude by suggesting that that an imbalance between pro-inflammatory/pro-oxidative and antioxidant events in genetically predisposed individuals may influence the development of WMHs. 相似文献
50.
Gian-Pietro Di Sansebastiano Silvia Fornaciari Fabrizio Barozzi Gabriella Piro Laura Arru 《International journal of molecular sciences》2014,15(3):4565-4582
We investigated the effect of auxin and acetylcholine on the expression of the tomato expansin gene LeEXPA2, a specific expansin gene expressed in elongating tomato hypocotyl segments. Since auxin interferes with clathrin-mediated endocytosis, in order to regulate cellular and developmental responses we produced protoplasts from tomato elongating hypocotyls and followed the endocytotic marker, FM4-64, internalization in response to treatments. Tomato protoplasts were observed during auxin and acetylcholine treatments after transient expression of chimerical markers of volume-control related compartments such as vacuoles. Here we describe the contribution of auxin and acetylcholine to LeEXPA2 expression regulation and we support the hypothesis that a possible subcellular target of acetylcholine signal is the vesicular transport, shedding some light on the characterization of this small molecule as local mediator in the plant physiological response. 相似文献