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排序方式: 共有1159条查询结果,搜索用时 31 毫秒
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Dr. Anders Højgaard Hansen Henriette B. Christensen Dr. Sunil K. Pandey Dr. Eugenia Sergeev Alice Valentini Julia Dunlop Domonkos Dedeo Simone Fratta Dr. Brian D. Hudson Prof. Graeme Milligan Prof. Trond Ulven Prof. Elisabeth Rexen Ulven 《ChemMedChem》2021,16(21):3326-3341
Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties. 相似文献
143.
Manuel Gentiluomo Alice Luddi Annapaola Cingolani Marco Fornili Laura Governini Ersilia Lucenteforte Laura Baglietto Paola Piomboni Daniele Campa 《International journal of molecular sciences》2021,22(8)
Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2˗rs11125529 and decreased sperm motility (p = 0.03); PXK˗rs6772228 with a lower sperm count (p = 0.02); NAF1˗rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208˗rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process. 相似文献
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Joana Silva Celso Alves Alice Martins Patrícia Susano Marco Simes Miguel Guedes Stephanie Rehfeldt Susete Pinteus Helena Gaspar Amrico Rodrigues Mrcia Ines Goettert Amparo Alfonso Rui Pedrosa 《International journal of molecular sciences》2021,22(4)
Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells’ exposure to 6-OHDA in the presence of Loliolide led to an increase of cells’ viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential. 相似文献
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Dr. Francesco A. Greco Dr. Elisa Albini Dr. Alice Coletti Dr. Daniela Dolciami Prof. Andrea Carotti Dr. Ciriana Orabona Prof. Ursula Grohmann Prof. Antonio Macchiarulo 《ChemMedChem》2019,14(24):2084-2092
Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the oxidative cleavage of l -Tryptophan (l -Trp) to yield N-formyl-kynurenine in the first and rate limiting step of the kynurenine pathway. Bioactive metabolites, involved in the regulation of important immunological responses and neurological processes, are then produced by downstream enzymes along the pathway. Inhibitors of IDO1 are being designed and developed as therapeutic agents for immuno-oncology. In this work, we investigated the molecular recognition path of l -Trp to IDO1, integrating biophysical methods with supervised molecular dynamics (suMD) and mutagenesis experiments. Results allowed disclosing for the first time high and low dissociation constants of l -Trp to IDO1, and the presence of a metastable interaction site located at the upper part of a channel whose borders are defined by the EF-loop and the C-terminal part of the JK-loop. Collectively, our results provide new clues for the design of next-generation IDO1 ligands. 相似文献
149.
André F. Soares Alice R. Honorio Diana C. Nunes de Lima Alline A. L. Tribst 《International Journal of Food Science & Technology》2021,56(9):4428-4433
This study characterised the main sweet beverages and food products marketed in Brazil regarding (i) the addition of sugar/sweeteners, (ii) nutritional profile and (iii) sugar claims. Results revealed that most of the beverages had added sweeteners, while food products were mainly sweetened with sugar. Moreover, >90% of the powdered products had added sweeteners. ‘Zero sugar’ (46%) and ‘light’ (55%) were the most common sugar claims in sugar-free and reduced-sugar products, respectively. Powdered products, soya drinks and baked products included claims less frequently. Regarding the nutritional profile, beverages with sugar substitution had a proportionally greater reduction in the content of carbohydrates and calories (up to 99%, for both) in relation to food (<82% and <85%, respectively). The results suggest that reducing sugar in solid foods remains a greater challenge than in beverages and that this reduction has less impact on the final energy density of foods. 相似文献
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