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| 2. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 4. |
- Chudinova, E., et al.
(författare)
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Determination of the properties and loading efficiency of encapsulated BSA-FITC and dexamethasone for drug delivery systems
- 2019
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Ingår i: IOP Conference Series. - : Institute of Physics Publishing (IOPP).
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Konferensbidrag (refereegranskat)abstract
- In this work porous microparticles of calcium carbonate were synthesized with bovine serum albumin - fluorescein isothiocyanate conjugate (BSA-FITC) and dexamethasone, and then used for encapsulation in polymer microcapsules by means of layer-by-layer assembly (LbL). The properties of the obtained microcapsules were characterized by scanning electron microscopy, dynamic light scattering, infrared-, ultraviolet- and visible spectroscopy. According to the performed DLS measurements, an average hydrodynamic diameter ranged from 4 to 8 m and zeta-potential for all types of capsules was determined as -18 and -21 mV. BSA-FITC was encapsulated using this approach yielded a loading efficiency of 49 % protein. This value calculated for dexamethasone was of 38%. The microcapsules filled with an encapsulated drug may find applications in the field of biotechnology, biochemistry, and medicine.
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| 5. |
- Chudinova, E., et al.
(författare)
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Functionalization of additive-manufactured Ti6Al4V scaffolds with poly(allylamine hydrochloride)/poly(styrene sulfonate) bilayer microcapsule system containing dexamethasone
- 2021
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Ingår i: Materials Chemistry and Physics. - : Elsevier BV. - 0254-0584 .- 1879-3312. ; 273
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Tidskriftsartikel (refereegranskat)abstract
- Porous titanium alloy Ti6Al4V scaffolds manufactured via electron beam melting (EBM®) reveal broad prospects for applications in bone tissue engineering. However, local inflammation and even implant failure may occur while placing an implant into the body. Thus, the application of drug carriers to the surface of a metallic implant can provide treatment at the inflammation site. In this study, we propose to use polyelectrolyte (PE) microcapsules formed by layer-by-layer (LbL) synthesis loaded with both porous calcium carbonate (CaCO3) microparticles and the anti-inflammatory drug dexamethasone (DEX) to functionalize implant surfaces and achieve controlled drug release. Scanning electron microscopy indicated that the CaCO3 microparticles coated with PE bilayers loaded with DEX had a spherical shape with a diameter of 2.3 ± 0.2 μm and that the entire scaffold surface was evenly coated with the microcapsules. UV spectroscopy showed that LbL synthesis allows the manufacturing of microcapsules with 40% DEX. According to high performance liquid chromatography (HPLC) analysis, 80% of the drug was released within 24 h from the capsules consisting of three bilayers of polystyrene sulfonate (PSS) and poly(allylamine)hydrochloride (PAH). The prepared scaffolds functionalized with CaCO3 microparticles loaded with DEX and coated with PE bilayers showed hydrophilic surface properties with a water contact angle below 5°. Mouse embryonic fibroblast cells were seeded on Ti6Al4V scaffolds with and without LbL surface modification. The surface modification with LbL PE microcapsules with CaCO3 core affected cell morphology in vitro. The results confirmed that DEX had no toxic effect and did not prevent cell adhesion and spreading, thus no cytotoxic effect was observed, which will be further studied in vivo.
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| 6. |
- Ehrenbolger, Kai, et al.
(författare)
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Differences in structure and hibernation mechanism highlight diversification of the microsporidian ribosome
- 2020
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Ingår i: PLoS biology. - : Public Library of Science. - 1544-9173 .- 1545-7885. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- Assembling and powering ribosomes are energy-intensive processes requiring fine-tuned cellular control mechanisms. In organisms operating under strict nutrient limitations, such as pathogenic microsporidia, conservation of energy via ribosomal hibernation and recycling is critical. The mechanisms by which hibernation is achieved in microsporidia, however, remain poorly understood. Here, we present the cryo-electron microscopy structure of the ribosome from Paranosema locustae spores, bound by the conserved eukaryotic hibernation and recycling factor Lso2. The microsporidian Lso2 homolog adopts a V-shaped conformation to bridge the mRNA decoding site and the large subunit tRNA binding sites, providing a reversible ribosome inactivation mechanism. Although microsporidian ribosomes are highly compacted, the P. locustae ribosome retains several rRNA segments absent in other microsporidia, and represents an intermediate state of rRNA reduction. In one case, the near complete reduction of an expansion segment has resulted in a single bound nucleotide, which may act as an architectural co-factor to stabilize a protein-protein interface. The presented structure highlights the reductive evolution in these emerging pathogens and sheds light on a conserved mechanism for eukaryotic ribosome hibernation.
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| 7. |
- Graham, Jesse R., et al.
(författare)
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The pipeline project: Pre-publication independent replications of a single laboratory's research pipeline
- 2016
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Ingår i: Journal of Experimental Social Psychology. - : Elsevier. - 1096-0465 .- 0022-1031. ; 66, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had “in the pipeline” as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed.
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| 8. |
- Palin, K, et al.
(författare)
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Contribution of allelic imbalance to colorectal cancer
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3664-
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Tidskriftsartikel (refereegranskat)abstract
- Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
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| 9. |
- Smelov, V, et al.
(författare)
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Beta and gamma human papillomaviruses in anal and genital sites among men: prevalence and determinants
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8241-
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Tidskriftsartikel (refereegranskat)abstract
- Data regarding the anogenital distribution of and type-specific concordance for cutaneous β- and γ-HPV types in men who have sex with women is limited and geographically narrow. Knowledge of determinants of anogenital detection of cutaneous HPV types in different regions is needed for better understanding of the natural history and transmission dynamics of HPV, and its potential role in the development of anogenital diseases. Genital and anal canal samples obtained from 554 Russian men were screened for 43 β-HPVs and 29 γ-HPVs, using a multiplex PCR combined with Luminex technology. Both β- and γ-HPVs were more prevalent in the anal (22.8% and 14.1%) samples than in the genital (16.8% and 12.3%) samples. Low overall and type-specific concordance for β-HPVs (3.5% and 1.1%) and γ-HPVs (1.3% and 0.6%) were observed between genital and anal samples. HIV-positive men had higher anal β- (crude OR = 12.2, 95% CI: 5.3–28.1) and γ-HPV (crude OR = 7.2, 95% CI: 3.3–15.4) prevalence than HIV-negative men. Due to the lack of genital samples from the HIV-positive men, no comparison was possible for HIV status in genital samples. The lack of type-specific positive concordance between genital and anal sites for cutaneous β- and γ-HPV types in heterosexual men posits the needs for further studies on transmission routes to discriminate between contamination and true HPV infection. HIV-positive status may favor the anal acquisition or modify the natural history of cutaneous HPV types.
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