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| 2. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Henning-Knechtel, Anja, et al.
(author)
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Designed Cell-Penetrating Peptide Inhibitors of Amyloid-beta Aggregation and Cytotoxicity
- 2020
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In: Cell Reports Physical Science. - : Elsevier BV. - 2666-3864. ; 1:2
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Journal article (peer-reviewed)abstract
- Amyloid proteins and peptides are a major contributing factor to the development of various neurodegenerative disorders, including Alzheimer’s and prion diseases. Previously, a designed cell-penetrating peptide (CPP) comprising a hydrophobic signal sequence followed by a prion protein (PrP)-derived polycationic sequence (PrP23–28: KKRPKP) was shown to have potent anti-prion properties. Here, we extend this approach toward the amyloid-beta (Aβ) peptide amyloid formation, which is associated with Alzheimer’s disease. We characterized the interactions of the CPP with Aβ using complementary in vitro and in silico experiments. We report that the CPP stabilizes Aβ in a non-amyloid state and inhibits Aβ-induced neurotoxicity. Moreover, replacing PrP23–28 with a corresponding segment from Aβ results in a construct with similar CPP functionality and antagonism of Aβ aggregation and neurotoxicity. Our findings reveal a general underlying principle for inhibition of pathogenic protein aggregation that may facilitate the design of CPP-based therapeutics for amyloid diseases.
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| 4. |
- Hunashal, Yamanappa, et al.
(author)
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Approaching Protein Aggregation and Structural Dynamics by Equilibrium and Nonequilibrium Paramagnetic Perturbation
- 2022
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:31, s. 10949-10958
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Journal article (peer-reviewed)abstract
- PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation) is the presented nuclear magnetic resonance (NMR) approach to identify at once the location of proteins' exposed surface, hindered accessibility, and exchange processes occurring on a mu s-ms time scale. In addition to mapping the protein surface accessibility, the application of this method under specific conditions makes it possible to distinguish conformational mobility and chemical exchange processes, thereby providing an alternative to characterization by more demanding techniques (transverse relaxation dispersion, saturation transfer, and high-pressure NMR). Moreover, its high sensitivity enables studying samples at low, physiologically more relevant concentrations. Association, dynamics, and oligomerization are addressed by PENELOP for a component of SARS-CoV-2 replication transcription complex and an amyloidogenic protein.
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| 5. |
- Landi, Antonio, et al.
(author)
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Transient vs In-Hospital Persistent AcuteKidney Injury in Patients With Acute Coronary Syndrome.
- 2023
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In: JACC. Cardiovascular interventions. - : Elsevier BV. - 1876-7605 .- 1936-8798. ; 16:2, s. 193-205
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Journal article (peer-reviewed)abstract
- The occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ.The aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS.In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding.Persistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95%CI: 1.48-3.64; P< 0.001; NACE: adjusted HR: 2.29; 95%CI: 1.48-3.52; P< 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95%CI: 2.03-5.82; P< 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria.Among patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627).
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| 6. |
- Silverio, Angelo, et al.
(author)
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Validation of the academic research consortium high bleeding risk criteria in patients undergoing percutaneous coronary intervention : A systematic review and meta-analysis of 10 studies and 67,862 patients
- 2022
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In: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 347, s. 8-15
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Research review (peer-reviewed)abstract
- Background: To assess the performance of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in stratifying the risk of bleeding and ischaemic events after percutaneous coronary intervention (PCI).Methods: MEDLINE, COCHRANE, Web of Sciences, and SCOPUS were searched for studies aimed at validating the ARC-HBR criteria in patients treated with PCI. The primary outcome measure of this meta-analysis was major bleeding.Results: The analysis included 10 studies encompassing 67,862 patients undergoing PCI; the HBR definition was fulfilled in 44.7% of the cases. The risk of major bleeding was significantly higher in HBR vs. Non-HBR group (RR, 2.56, 95% CI 2.28-2.89). The average C-statistic was 0.64 (95% CI 0.60-0.68), indicating modest discrimination. The risk of intracranial hemorrhage, gastrointestinal bleeding, fatal bleeding, ischaemic stroke, cardiac death and all-cause death was higher in HBR vs. Non-HBR group. Despite a higher incidence of myocardial infarction and stent thrombosis in patients deemed at HBR, the rate of target lesion revascularization was comparable between groups (RR, 1.01, 95% CI 0.88-1.16). The mean effect size for the cumulative incidence of major bleeding exceeded the HBR cut-off value of 4% for all major criteria except one, and for two out of six minor criteria, namely age >= 75 years and moderate CKD.Conclusion: The ARC-HBR definition identifies patients at higher risk of major bleeding and other adverse cardiovascular events after PCI. Almost all major criteria, but also two of the minor criteria, were individually associated with rates of major bleeding above 4% thus fulfilling the definition of major HBR criteria.
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| 7. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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