Vernunft und Temperament

Gunnarsson, Logi; Braungart, Anna

doi:10.30965/9783957437402

Cited by 7 publications

(6 citation statements)

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“…The pentasulfated quercetin (SQ) 6 and its regioisomer, the pentasulfated morin (SMo) 7 (Figure 4) were also found to bind ATIII with K D values of 17 and 1.8 µM (Table 2), respectively, at pH 6.0. They also accelerated the ATIII-mediated inhibition of FXa by 17.5-and 21.8-fold, respectively [63]. In a similar study, the pentasulfated flavonoids indirectly inhibited FXa by 82-89% whereas the tetrasulfated and trisulfated flavonoids inhibited FXa by 40-60% and 0-12%, respectively [64].…”

Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 88%

“…They also accelerated the ATIII-mediated inhibition of FXa by 17.5-and 21.8-fold, respectively [63]. In a similar study, the pentasulfated flavonoids indirectly inhibited FXa by 82-89% whereas the tetrasulfated and trisulfated flavonoids inhibited FXa by 40-60% and 0-12%, respectively [64]. Hydropathic interaction analyses of the nonsaccharidic activators binding to ATIII predicted more favorable interaction of most of the above activators, except (−)-catechin sulfate ((−)-CS) 8 (Figure 4), with the activated form of ATIII than with the native ATIII form supporting the fact that these molecules work as ATIII activators [65].…”

Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 90%

“…Kinetic studies indicated that ECS binds ATIII with K D values of 10.5 and 66 µM at pH 6.0, I 0.025, and pH 7.4, I 0.035, respectively, (Table 2) which compared well with 2 and 80 µM, respectively, observed for DEF. However, ECS accelerated the ATIII inhibition of FXa only 8-fold as compared to the ~300-fold observed with DEF [61]. Subsequently, two more analogs of ECS were synthesized and tested for ATIII activation.…”

Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 96%

“…Among the multiple GAG-serpin interaction platforms, heparin-ATIII interface has served as a novel platform to design and develop new anticoagulants that address the different issues related to the clinical use of heparins. Particularly, sulfated flavonoids [61][62][63][64][65] and tetrahydroisoquinolines (THIQs) [66][67][68] were designed as ATIII activators and indirect FXa inhibitors. Details are provided in subsequent sections.…”

Section: A) Serine Protease Inhibitors (Serpins)mentioning

confidence: 99%

“…This suggested that nonionic forces contributed 55-73% of the binding energy in the case of nonsaccharide activators compared to 40-60% in the case of DEFGH. Moreover, competition studies with a tetrasaccharide EFGH" and low affinity heparin indicated that the small nonsaccharide activators may bind in the extended heparin-binding site and not in the pentasaccharide-binding site [62]. The pentasulfated quercetin (SQ) 6 and its regioisomer, the pentasulfated morin (SMo) 7 (Figure 4) were also found to bind ATIII with K D values of 17 and 1.8 µM (Table 2), respectively, at pH 6.0.…”

Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 99%

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Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies

Afosah¹,

Al‐Horani

2020

CMC

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Glycosaminoglycans (GAGs) are very complex, natural anionic polysaccharides. They are polymers of repeating disaccharide units of uronic acid and hexosamine residues. Owing to their template-free, spatiotemporally-controlled, and enzyme-mediated biosyntheses, GAGs possess enormous polydispersity, heterogeneity, and structural diversity which often translate into multiple biological roles. It is well documented that GAGs contribute to physiological and pathological processes by binding to proteins including serine proteases, serpins, chemokines, growth factors, and microbial proteins. Despite advances in the GAG field, the GAG-protein interface remains largely unexploited by drug discovery programs. Thus, Non-Saccharide Glycosaminoglycan Mimetics (NSGMs) have been rationally developed as a novel class of sulfated molecules that modulate GAG-protein interface to promote various biological outcomes of substantial benefit to human health. In this review, we describe the chemical, biochemical, and pharmacological aspects of recently reported NSGMs and highlight their therapeutic potentials as structurally and mechanistically novel anti-coagulants, anti-cancer agents, anti-emphysema agents, and anti-viral agents. We also describe the challenges that complicate their advancement and describe ongoing efforts to overcome these challenges with the aim of advancing the novel platform of NSGMs to clinical use.

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Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 88%

Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 90%

Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 96%

Section: A) Serine Protease Inhibitors (Serpins)mentioning

confidence: 99%

Section: A) Sulfated Nsgm-based Allosteric Modulators Of Coagulation and Fibrinolysis Proteinsmentioning

confidence: 99%

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Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies

Afosah¹,

Al‐Horani

2020

CMC

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Lipid and protein corona of food-grade TiO2 nanoparticles in simulated gastrointestinal digestion

et al. 2020

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In the presence of biological matrices, engineered nanomaterials, such as TiO 2 , develop a biomolecular corona composed of lipids, proteins, etc. In this study, we analyzed the biocorona formed on the food grade TiO 2 (E171) going through an in vitro simulated gastrointestinal digestion system in either a fasting food model (FFM), a standardized food model (SFM), or a high fat food model (HFFM). Lipids and proteins were extracted from the biocorona and underwent untargeted lipidomic and label-free shotgun proteomic analyses. Our results showed that the biocorona composition was different before and after food digestion. After digestion, more diverse lipids were adsorbed compared to proteins, most of which were the enzymes added to the simulated digestion system. The corona lipid profile was distinct from the digested food model they presented in, although similarity in the lipid profiles between the corona and the food matrix increased with the fat content in the food model. The corona formed in the two low-fat environments of FFM and SFM shared a higher degree of similarity while very different from their corresponding matrix, with some lipid species adsorbed with high enrichment factors, indicating specific interaction with the TiO 2 surface outperforming lipid matrix concentration in determination of corona formation. Formation of the biocorona may have contributed to the reduced oxidative stress as well as toxicological impacts observed in cellular studies. The present work is the first to confirm persistent adsorption of biomolecules could occur on ingested *

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Wir müssen abwägen – aber wie sollen wir abwägen?

Wingert

2021

Deutsche Zeitschrift Für Philosophie

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The global Covid-19 crisis raises at least three moral questions, which my contribution answers as follows: (1) Which patient should get treatment according to triage criteria? The patient whose treatment has the best prospect of success. (2) How should we resolve the conflict between public health measures and economic needs? Public health should have priority, but reaches its limits where the individual right to stay afloat through one’s own work is violated. (3) How should we resolve the conflict between public health measures and civil liberties? Public health should have priority, but reaches its limits where the restriction of freedom violates the integrity of individual health and personal freedom. The answers and the arguments behind these are developed through the discussion of a wide range of current public health policies, concrete measures, and competing approaches to moral questions in the Covid-19 pandemic.

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Vernunft und Temperament

Cited by 7 publications

References 0 publications

Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies

Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies

Lipid and protein corona of food-grade TiO2 nanoparticles in simulated gastrointestinal digestion

Wir müssen abwägen – aber wie sollen wir abwägen?

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