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排序方式: 共有1647条查询结果,搜索用时 15 毫秒
71.
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
72.
73.
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
74.
J. B. Copetti E. Lorenzo F. Chenlo 《Progress in Photovoltaics: Research and Applications》1993,1(4):283-292
A battery model is proposed as a tool to simulate and optimize photovoltaic (PV) / storage systems. the normalized form of the equations with respect to the battery capacity allows us to generalize its use for any type and size of lead-acid batteries. The validity of this model to represent the battery voltage evolution during charge, overcharge and discharge processes and to predict the performance of solar systems under different operational conditions is analysed. Moreover, the battery efficiency losses are presented as a function of the upper regulation thresholds of the charge controllers and the size of the array and storage systems in a domestic application in the climate of Madrid. 相似文献
75.
This paper submits a systematic analysis of user consumption patterns of several photovoltaic (PV)-powered rural dwellings in a Mediterranean area of Spain. the measurements have been carried out within the framework of two projects and assessed in contrast with other experiences. This analysis allows a consumption scenario developed previsouly to be tested by means of the classification of families according to the number and age of their members into three types—extended, mean and reduced—with the aim of establishing a few standard cases of optimization for sizing purposes. Because the use of AC current is indispensable, at least for domestic appliances, the scenario hereby proposed leads to PV system sizes of 160, 320 and 480 Wp for reduced, mean and extended families, respectively, enjoying a level of comfort similar to grid-conneced systems. 相似文献
76.
Giulia Sierri Roberta Dal Magro Barbara Vergani Biagio Eugenio Leone Beatrice Formicola Lorenzo Taiarol Stefano Fagioli Marcelo Kravicz Lucio Tremolizzo Laura Calabresi Francesca Re 《International journal of molecular sciences》2022,23(1)
The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ1-42-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs. 相似文献
77.
The role of inner-layer (interphase) in fiber-reinforced composites is often assessed by measuring the interfacial shear strength of single fibers embedded in matrix blocks. Interfacial shear strength is calculated using simple shear lag analyses (Kelly and Tyson model). This paper shows that application of Kelly and Tyson's equation may result in gross overprediction of interfacial shear strengths if the thickness of the inner-layer is not negligible in comparison with the fiber diameter. 相似文献
78.
Zhiyuan Jiang Peng Liu Qihui Chen Hung-Jue Sue Tim Bremner Lorenzo P. DiSano 《应用聚合物科学杂志》2020,137(33):48966
Interest in developing high-performance blends for niche applications has grown significantly in efforts to meet ever-increasing harsh environment demands. In this work, four model poly(aryl-ether-ketone)/polybenzimidazole (PAEK/PBI) blends were chosen to study the influence of premixing methods, processing, and matrix polymers, on their mechanical properties. Among the model poly(ether ether ketone) (PEEK) and PBI blends, mechanical properties are greatly enhanced by melt premixing. The molding process mainly affects the matrix crystallinity, which in turn greatly influences fracture toughness of the blend. Poly(ether ketone ketone) (PEKK) and PBI blend exhibits a slightly lower tensile strength and fracture toughness than PEEK/PBI due to the differences in inherent properties of PEEK and PEKK matrices and their interfacial interaction with PBI. The processing−structure–property relationship of PAEK/PBI blends is established to help guide optimal design of high-performance polymer blends for structural applications. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48966. 相似文献
79.
Angelo Cichelli Ylenia Riciputi Lorenzo Cerretani Maria F. Caboni Nicola d'Alessandro 《Journal of the American Oil Chemists' Society》2020,97(1):15-23
A series of authentic virgin, refined, and mixtures of olive oils was analyzed for their content of 2-and 3-chloropropanediol (MCPD) esters expressed as 2−/3-MCPD, glycidol (and related glycidyl esters) (GE), and diglycerides (DAG). High concentrations of MCPD and GE were found, above all, in pomace oils, which come from the poorer starting raw materials, while virgin olive oils, as expected, do not contain any process contaminant. On the other hand, DAGs are present in all samples, demonstrating that their involvement in the formation of such contaminants only occurs when temperatures are higher than that used during the refining steps. The lack of correlation between the amounts of MCPD and GE can be ascribed to their completely different chemical stability as the epoxy ring of the GE opens easily, leading to both short-chain derivatives and/or MCPD itself. This finding can also explain the data about the absence of 2-MCPD in all the analyzed oil samples: other than the statistical probability and the steric effect of the SN2 formation mechanism, both in favor of the 3- derivative, we have also to consider the MCPD formation pathway involving glycidol that, under opportune conditions of refining, can increase the whole amount of 3-MCPD (under thermodynamic control, 3-MCPD is more stable). 相似文献
80.
Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid
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Dr. Anna K. Stavrinides Dr. Evangelos C. Tatsis Dr. Thu‐Thuy Dang Dr. Lorenzo Caputi Dr. Clare E. M. Stevenson Dr. David M. Lawson Dr. Bernd Schneider Prof. Sarah E. O'Connor 《Chembiochem : a European journal of chemical biology》2018,19(9):940-948
Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids (Catharanthus roseus and Rauvolfia serpentina) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence‐based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches. 相似文献