| 1. |
- Babenko, Vladislav V., et al.
(författare)
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Draft genome sequences of Hirudo medicinalis and salivary transcriptome of three closely related medicinal leeches
- 2020
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSalivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today.ResultsWe annotated the Hirudo medicinalis genome and performed RNA-seq on salivary cells isolated from three closely related leech species, H. medicinalis, Hirudo orientalis, and Hirudo verbana. Differential expression analysis verified by proteomics identified salivary cell-specific gene expression, many of which encode previously unknown salivary components. However, the genes encoding known anticoagulants have been found to be expressed not only in salivary cells. The function-related analysis of the unique salivary cell genes enabled an update of the concept of interactions between salivary proteins and components of haemostasis.ConclusionsHere we report a genome draft of Hirudo medicinalis and describe identification of novel salivary proteins and new homologs of genes encoding known anticoagulants in transcriptomes of three medicinal leech species. Our data provide new insights in genetics of blood-feeding lifestyle in leeches.
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| 2. |
- Maslov, Ivan O., et al.
(författare)
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Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4)
- 2022
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Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Compounds that contain (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors. Compound 12a (IC50 = 16.8 +/- 2.2 nM), named neogliptin, is a more potent DPP-4 inhibitor than vildagliptin and sitagliptin. Neogliptin interacts with key DPP-4 residues in the active site and has pharmacophore parameters similar to vildagliptin and sitagliptin. It was found to have a low cardiotoxic effect compared to sitagliptin, and it is superior to vildagliptin in terms of ADME properties. Moreover, compound 12a is stable in aqueous solutions due to its low intramolecular cyclisation potential. These findings suggest that compound 12a has unique properties and can act as a template for further type 2 diabetes mellitus drug development.
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| 3. |
- Arslanov, Temirlan R., et al.
(författare)
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Pressure control of magnetic clusters in strongly inhomogeneous ferromagnetic chalcopyrites
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 7720-
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Tidskriftsartikel (refereegranskat)abstract
- Room-temperature ferromagnetism in Mn-doped chalcopyrites is a desire aspect when applying those materials to spin electronics. However, dominance of high Curie-temperatures due to cluster formation or inhomogeneities limited their consideration. Here we report how an external perturbation such as applied hydrostatic pressure in CdGeP2:Mn induces a two serial magnetic transitions from ferromagnet to non-magnet state at room temperature. This effect is related to the unconventional properties of created MnP magnetic clusters within the host material. Such behavior is also discussed in connection with ab initio density functional calculations, where the structural properties of MnP indicate magnetic transitions as function of pressure as observed experimentally. Our results point out new ways to obtain controlled response of embedded magnetic clusters.
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| 4. |
- Dahlén, Amelia, et al.
(författare)
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Trends in Antidiabetic Drug Discovery : FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales
- 2022
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) continues to be a substantial medical problem due to its increasing global prevalence and because chronic hyperglycemic states are closely linked with obesity, liver disease and several cardiovascular diseases. Since the early discovery of insulin, numerous antihyperglycemic drug therapies to treat diabetes have been approved, and also discontinued, by the United States Food and Drug Administration (FDA). To provide an up-to-date account of the current trends of antidiabetic pharmaceuticals, this review offers a comprehensive analysis of the main classes of antihyperglycemic compounds and their mechanisms: insulin types, biguanides, sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors (AGIs), thiazolidinediones (TZD), incretin-dependent therapies, sodium-glucose cotransporter type 2 (SGLT2) inhibitors and combinations thereof. The number of therapeutic alternatives to treat T2DM are increasing and now there are nearly 60 drugs approved by the FDA. Beyond this there are nearly 100 additional antidiabetic agents being evaluated in clinical trials. In addition to the standard treatments of insulin therapy and metformin, there are new drug combinations, e.g., containing metformin, SGLT2 inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors, that have gained substantial use during the last decade. Furthermore, there are several interesting alternatives, such as lobeglitazone, efpeglenatide and tirzepatide, in ongoing clinical trials. Modern drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists, DPP4 inhibitors and SGLT2 inhibitors have gained popularity on the pharmaceutical market, while less expensive over the counter alternatives are increasing in developing economies. The large heterogeneity of T2DM is also creating a push towards more personalized and accessible treatments. We describe several interesting alternatives in ongoing clinical trials, which may help to achieve this in the near future.
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