| 41. |
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| 42. |
- Altay, Özlem, et al.
(författare)
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Current Status of COVID-19 Therapies and Drug Repositioning Applications
- 2020
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Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
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Tidskriftsartikel (refereegranskat)abstract
- The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.
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| 43. |
- Izsak, Julia, et al.
(författare)
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Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Lithium salts are used as mood-balancing medication prescribed to patients suffering from neuropsychiatric disorders, such as bipolar disorder and major depressive disorder. Lithium salts cross the blood-brain barrier and reach the brain parenchyma within few hours after oral application, however, how lithium influences directly human neuronal function is unknown. We applied patch–clamp and microelectrode array technology on human induced pluripotent stem cell (iPSC)-derived cortical neurons acutely exposed to therapeutic (<1 mM) and overdose concentrations (>1 mM) of lithium chloride (LiCl) to assess how therapeutically effective and overdose concentrations of LiCl directly influence human neuronal electrophysiological function at the synapse, single-cell, and neuronal network level. We describe that human iPSC-cortical neurons exposed to lithium showed an increased neuronal activity under all tested concentrations. Furthermore, we reveal a lithium-induced, concentration-dependent, transition of regular synchronous neuronal network activity using therapeutically effective concentration (<1 mM LiCl) to epileptiform-like neuronal discharges using overdose concentration (>1 mM LiCl). The overdose concentration lithium-induced epileptiform-like activity was similar to the epileptiform-like activity caused by the GABAA-receptor antagonist. Patch–clamp recordings reveal that lithium reduces action potential threshold at all concentrations, however, only overdose concentration causes increased frequency of spontaneous AMPA-receptor mediated transmission. By applying the AMPA-receptor antagonist and anti-epileptic drug Perampanel, we demonstrate that Perampanel suppresses lithium-induced epileptiform-like activity in human cortical neurons. We provide insights in how therapeutically effective and overdose concentration of lithium directly influences human neuronal function at synapse, a single neuron, and neuronal network levels. Furthermore, we provide evidence that Perampanel suppresses pathological neuronal discharges caused by overdose concentrations of lithium in human neurons.
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| 44. |
- Krupic, Ferid, et al.
(författare)
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The Influence of Age, Gender and Religion on Willingness to be an Organ Donor: Experience of Religious Muslims Living in Sweden.
- 2019
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Ingår i: Journal of religion and health. - : Springer Science and Business Media LLC. - 1573-6571 .- 0022-4197. ; 58, s. 847-859
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Tidskriftsartikel (refereegranskat)abstract
- The transplantation of organs is one of the most successful medical advances in recent decades, and transplantation is the treatment of choice for severe organ failure worldwide. Despite this situation and the general acknowledgment of organ donation (OD) as a global priority, the demand for organs outstrips the supply in virtually every country in the world. The study aims to elucidate whether age, gender and religion influence decision-making about organ donation in religious Muslims living in Sweden Data were collected through three group interviews using open-ended questions and qualitative content analysis. Twenty-seven participants, 15 males and 12 females from four countries, participated in the focus group interviews. The analysis of the collected data resulted in three main categories: "Information and knowledge about organ donation," "The priorities when deciding about organ donation" and "The religious aspects of organ donation," including a number of subcategories. Good information about and knowledge of OD, priorities in OD, importance of the fact that religion must be studied and taught daily and religious education were only a few of the factors informants emphasized as predictors of the total and successful donation of organs. Age, gender or religion did not have an impact on organ donation. High levels of education through religious education and good information via various media, as well as a good knowledge of the Swedish language, are predictors of improved OD. In order to overcome religious ideology as a source of misinformation relating to OD and to promote increased OD in the future, specific intervention studies and the improved involvement of religious communities and education in schools and the healthcare system are vital and must be a starting point for improved OD.
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| 45. |
- Mamontov, Eugen, 1955, et al.
(författare)
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The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
- 2006
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Ingår i: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
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Tidskriftsartikel (refereegranskat)abstract
- Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
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| 46. |
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| 47. |
- Lai, Kuei-Hung
(författare)
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Studies on anti-leukemic terpenoids from medicinal mushrooms and marine sponges with ChemGPS-NP-based targets investigation of lead compounds
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates the anti-leukemic activity of terpenoids isolated from medicinal mushrooms and marine sponges, as well as their possible targets and mechanisms of action.In the first section, we focused on studying the triterpenoidal components of three triterpenoid-enriched medicinal mushrooms Antrodia cinnamomea, Ganoderma lucidum, and Poria cocos, which have been used in folk medicine for centuries and also developed into several contemporary marketed products. We isolated the major and characteristic triterpenoids from these mushrooms, together with six new lanostanoids (II-1–II-6). The anti-leukemic activity of the isolates was evaluated in vitro using MTT proliferative assay and seven of them exhibited potential anti-leukemic effect. The active lead compounds were further subjected to computational analyses utilizing the ChemGPS-NP tool. We established a database for the anti-leukemic relevant chemical space of triterpenoids isolated from these three medicinal mushrooms, which could be used as a reference database for further research on anti-leukemic triterpenoids. Our results indicated that the anti-leukemic effect of the active lead compounds was mediated not only through topoisomerases inhibition but also through inhibiting DNA polymerases.The second and third sections focused on isolation of anti-leukemic sesterterpenoids from sponges. The investigation of Carteriospongia sp. led to the isolation of two new scalarane-type sesterterpenoids (III-1 and III-2) and one known tetraprenyltoluquinol-related metabolite (III-3). All isolates exhibit an apoptotic mechanism of action against Molt 4 cells, found to be mediated through the disruption of the mitochondrial membrane potential (MMP) and inhibition of topoisomerase IIα expression. Detailed investigation of the apoptotic mechanism of action using molecular docking analysis revealed that compound III-1 might target Hsp90 protein. The apoptotic-inducing effect of III-3 was supported by in vivo experiment by suppressing the volume of xenograft tumor growth (47.58%) compared with the control.In the final section of this thesis we studied manoalide and its derivatives, sesterterpenoids isolated from the sponge Luffariella sp.. Manoalide has been studied as a potential anti-inflammatory agent for the last thirty years with more than 200 publications and 40 patents. However, the configurations at positions 24 and 25 were never revealed. In the current study, ten manoalide-type sesterterpenoids (IV-1–IV-10) were isolated from Luffariella sp. and their stereoisomers at positions 24 and 25 were identified and separated for the first time. The configuration at positions 24 and 25 showed to have a significant effect on the anti-leukemic activity of manoalide derivatives, with the 24R,25S-isomer exhibiting the most potent anti-leukemic activity. The apoptotic mechanism of action of compound IV-7 against Molt 4 cells was investigated, and the compound was found to trigger MMP disruption and intracellular reactive oxygen species (ROS) generation. Compound IV-7 also inhibited activity against both human topoisomerases, I and II. The in vivo experiment further supported the anti-leukemic effect of IV-7 with a 66.11% tumor volume suppression compared to the control.
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| 48. |
- Arvidsson, Daniel, 1974, et al.
(författare)
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Re-examination of accelerometer data processing and calibration for the assessment of physical activity intensity.
- 2019
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 29:10, s. 1442-1452
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Tidskriftsartikel (refereegranskat)abstract
- This review reexamines use of accelerometer and oxygen uptake data for assessment of activity intensity. Accelerometers capture mechanical work, while oxygen uptake captures the energy cost of this work. Frequency filtering needs to be considered when processing acceleration data. A too restrictive filter attenuates the acceleration signal for walking and, to a higher degree, for running. This measurement error affects shorter (children) more than taller (adults) individuals due to their higher movement frequency. Less restrictive filtering includes more movement related signals and provide measures that better capture mechanical work, but may include more noise. An optimal filter cut-point is determined where most relevant acceleration signals are included. Further, accelerometer placement affects what part of mechanical work being captured. While the waist placement captures total mechanical work and therefore contributes to measures of activity intensity equivalent by age and stature, the thigh and wrist placements capture more internal work and do not provide equivalent measures. Value calibration of accelerometer measures is usually performed using measured oxygen uptake with the metabolic equivalent of task (MET) as reference measure of activity intensity. However, the use of MET is not stringent and is not a measure of activity intensity equivalent by age and stature. A candidate measure is the mass-specific net oxygen uptake, VO2 net (VO2 tot - VO2 stand). To improve measurement of physical activity intensity using accelerometers, research developments are suggested concerning processing of accelerometer data, use of energy expenditure as reference for activity intensity, and calibration procedure with absolute versus relative intensity. This article is protected by copyright. All rights reserved.
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| 49. |
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| 50. |
- Groglopo, Adrián, 1967
(författare)
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Hälsa, vård och strukturell diskriminering
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Antologin behandlar den strukturella diskrimineringens inverkan på hälsotillstånd samt tillgång till en adekvat hälsa- och sjukvård för personer med utländsk bakgrund. Antologins olika bidrag ger viktiga insikter om hur den strukturella diskrimineringen tar sig uttryck och om dess konsekvenser.
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