SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) srt2:(2020-2022)"

Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) > (2020-2022)

  • Resultat 1-10 av 539
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Izsak, Julia, et al. (författare)
  • Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function
  • 2021
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11
  • 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.
  •  
2.
  • Mohammadi, Elyas, et al. (författare)
  • Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:9, s. 1-24
  • Forskningsöversikt (refereegranskat)abstract
    • Simple Summary Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug-target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches.
  •  
3.
  • Altay, Özlem, et al. (författare)
  • Current Status of COVID-19 Therapies and Drug Repositioning Applications
  • 2020
  • Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
  • 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.
  •  
4.
  • Engdahl, Elin, et al. (författare)
  • Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)
  • 2021
  • Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA's known impact on neurodevelopment.
  •  
5.
  • Albofetileh, Mehdi, et al. (författare)
  • Seaweed Proteins as a Source of Bioactive Peptides
  • 2021
  • Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1873-4286 .- 1381-6128. ; 27:11, s. 1342 -1352
  • Forskningsöversikt (refereegranskat)abstract
    • Seaweeds have gained great attention as a vegetarian and sustainable marine source of protein which do not need irrigation, arable land and fertilization. Besides, seaweeds are considered as an untapped resource for discovering bioactive compounds with health benefits where bioactive peptides have shown outstanding potential. This review provides a detailed overview of available scientific knowledge on production methods, bioactivity and application of peptides from seaweed proteins. The emphasize is on the effects form seaweed varieties and peptide production condition on the bioactivity of the peptides and their potential health benefits. Bioactive properties of seaweed peptides including antioxidant, antihypertensive, antidiabetic, anti-inflammatory, anticancer activities and other potential health benefits have been discussed. It also covers current challenges and required future research and innovations for the successful application of seaweeds proteins as a sustainable source of bioactive peptides. Effects from seasonal variation of seaweed composition on the bioactivity of their peptides, difficulties in the extraction of proteins from seaweed complex structure, scalability and reproducibility of the developed methods for the production of bioactive peptides, the safety of the peptides are examples of highlighted challenges. Further studies on the bioavailability of the seaweed bioactive peptides and validation of the results in animal models and human trials are needed before their application as functional foods or pharmaceutical ingredients.
  •  
6.
  • Holmbäck, Jan, et al. (författare)
  • Preclinical development of sodium fusidate antibiotic cutaneous spray based on water-free lipid formulation system
  • 2022
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 176
  • Tidskriftsartikel (refereegranskat)abstract
    • Topical antibiotics are a key component in the management of mild to moderate skin and soft tissue infections. There are, however, concerns about the emerging bacterial resistance against topical antibacterial agents such as fusidic acid, due to the prolonged treatment period of its marketed dosage forms. Improving the efficacy of topical formulations could potentially shorten the treatment period and avoid the resistance growth. To provide a more effective drug delivery, a water-free lipid-based formulation system (AKVANO (R)) which can be applied by spraying, has been developed. In the current paper, different formulations containing sodium fusidate were evaluated for their in vitro skin permeability using artificial skin mimicking membranes and antibacterial properties using ex vivo and in vivo skin wound infection models. The novel formulations containing sodium fusidate showed a much higher skin permeation (up to 60% of nominal amount) than the commercially available Fucidin (R) cream (3%). These formulations also gave a significantly stronger antibacterial effect than Fucidin cream showing a clear dose-response relationship for the sodium fusidate content. A spray product based on the described formulation technology would therefore require a shorter treatment time and thereby lower the risk for the development of bacterial resistance. Spray administration of these formulations provides an even layer on the skin surface from which the solvent quickly evaporates and thereby facilitates a non-touch application where no rubbing is required.
  •  
7.
  • Mitra, Sanhita, et al. (författare)
  • Subcellular distribution of p53 by the p53-responsive lncRNA NBAT1 determines chemotherapeutic response in neuroblastoma.
  • 2021
  • Ingår i: Cancer research. - 1538-7445. ; 81:6, s. 1457-1471
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroblastoma has a low mutation rate for the p53 gene. Alternative ways of p53 inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation of wild-type p53. However, mechanisms leading to p53 inactivation via cytoplasmic accumulation are not well investigated. Here we show that the neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor NBAT1 is a p53-responsive lncRNA that regulates p53 subcellular levels. Low expression of NBAT1 provided resistance to genotoxic drugs by promoting p53 accumulation in cytoplasm and loss from mitochondrial and nuclear compartments. Depletion of NBAT1 altered CRM1 function and contributed to the loss of p53-dependent nuclear gene expression during genotoxic drug treatment. CRM1 inhibition rescued p53-dependent nuclear functions and sensitized NBAT1-depleted cells to genotoxic drugs. Combined inhibition of CRM1 and MDM2 was even more effective in sensitizing aggressive neuroblastoma cells with p53 cytoplasmic accumulation. Thus, our mechanistic studies uncover an NBAT1-dependent CRM1/MDM2-based potential combination therapy for high-risk neuroblastoma patients.
  •  
8.
  • Näslund, Jakob, et al. (författare)
  • Expression of 22 serotonin-related genes in rat brain after sub-acute serotonin depletion or reuptake inhibition
  • 2020
  • Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 32:3, s. 159-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Although the assessment of expression of serotonin-related genes in experimental animals has become a common strategy to shed light on variations in brain serotonergic function, it remains largely unknown to what extent the manipulation of serotonin levels causes detectable changes in gene expression. We therefore chose to investigate how sub-acute depletion or elevation of brain serotonin influences the expression of a number of serotonin-related genes in six brain areas. Methods: Male Wistar rats were administered a serotonin synthesis inhibitor, para-chlorophenylalanine (p-CPA), or a serotonin reuptake inhibitor, paroxetine, for 3 days and then sacrificed. The expression of a number of serotonin-related genes in the raphe nuclei, hypothalamus, amygdala, striatum, hippocampus and prefrontal cortex was investigated using real-time quantitative PCR (rt-qPCR). Results: While most of the studied genes were uninfluenced by paroxetine treatment, we could observe a robust downregulation of tryptophan hydroxylase-2 in the brain region where the serotonergic cell bodies reside, that is, the raphe nuclei. p-CPA induced a significant increase in the expression of Htr1b and Htr2a in amygdala and of Htr2c in the striatum and a marked reduction in the expression of Htr6 in prefrontal cortex; it also enhanced the expression of the brain-derived neurotrophic factor (Bdnf) in raphe and hippocampus. Conclusion: With some notable exceptions, the expression of most of the studied genes is left unchanged by short-term modulation of extracellular levels of serotonin.
  •  
9.
  • Tripathi, Rekha, PhD student, 1985- (författare)
  • Unlocking the Role Of Orphan Solute Carrier SLC38A10 In Brain Metabolism : The SLC38A10 transporter in nutrient and metabolic regulation
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Membrane transporters are the primary gatekeepers of cells and regulate the transport of nutrients, metabolites, ions, water, and neurotransmitters into and across the human cells. The solute carrier transporters (SLCs) are the most prominent transporters, comprising 430 members divided into 65 subfamilies. SLCs are located on the plasma membrane and organelles such as mitochondria, vesicles, peroxisomes, endoplasmic reticulum, Golgi, and lysosomes. This thesis aimed to study SLCs of the SLC38 family under nutrient stress, focused particularly on the orphan SLC38A10 transporter.In Paper I, regulation of members of SLC38 family transporter, after amino acid starvation in mouse hypothalamic cells and primary cortex cells, was studied using microarrays and qPCR. We found several members of the SLC38 family that were strongly affected under amino acid starvation and showing a potential role in amino acid signaling in the brain. In Paper II, we performed a cellular and tissue localization and functional study of SLC38A10 transporter and revealed that SLC38A10 was expressed in both excitatory and inhibitory neurons in the mouse brain and has a unique subcellular localization in the ER and Golgi membrane. Furthermore, knockdown of the SLC38A10 gene resulted in reduced nascent protein synthesis in PC12 cells. Further, to unlock the biological function of the SLC38A10 transporter, in Paper III and Paper IV, we used SLC38A10 knockout mouse model.In Paper III, the goal was to uncover the role of SLC38A10 in acute glutamate and oxidative stress. Here, we found that a loss of SLC38A10 KO resulted in changes in the p53 levels and affected the mitochondrial function. Thus, this study established a possible role of SLC38A10 in cell survival, linked with p53, in mouse primary cortex cells. In Paper IV, we examined the role of SLC38A10 in amino acid metabolism and nutrient sensing in the mTOR signaling pathway. We performed complete amino acid starvation and refeed experiment on SLC38A10 knockout primary cortex cells. We concluded that SLC38A10 acts as a transceptor and regulates mTOR-dependent protein and lipid synthesis in brain cells, corroborating the findings from Paper II. To summarize, the present work has uncovered the function of SLC38A10 in the brain. It also provides knowledge of SLC38A10’s role in amino acid metabolism and signaling pathway(s). The findings of this thesis will enhance an understanding of SLC38A10 transporter and provide insight into future disease targeted drug studies focused on metabolic disorder and neurodegenerative disease.
  •  
10.
  • Yau, Estelle, et al. (författare)
  • Global Sensitivity Analysis of the Rodgers and Rowland Model for Prediction of Tissue: Plasma Partitioning Coefficients: Assessment of the Key Physiological and Physicochemical Factors That Determine Small-Molecule Tissue Distribution
  • 2020
  • Ingår i: AAPS Journal. - : Springer Nature. - 1550-7416. ; 22:2, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • In physiologically based pharmacokinetic (PBPK) modelling, the large number of input parameters, limited amount of available data and the structural model complexity generally hinder simultaneous estimation of uncertain and/or unknown parameters. These parameters are generally subject to estimation. However, the approaches taken for parameter estimation vary widely. Global sensitivity analyses are proposed as a method to systematically determine the most influential parameters that can be subject to estimation. Herein, a global sensitivity analysis was conducted to identify the key drug and physiological parameters influencing drug disposition in PBPK models and to potentially reduce the PBPK model dimensionality. The impact of these parameters was evaluated on the tissue-to-unbound plasma partition coefficients (Kpus) predicted by the Rodgers and Rowland model using Latin hypercube sampling combined to partial rank correlation coefficients (PRCC). For most drug classes, PRCC showed that LogP and fraction unbound in plasma (fup) were generally the most influential parameters for Kpu predictions. For strong bases, blood:plasma partitioning was one of the most influential parameter. Uncertainty in tissue composition parameters had a large impact on Kpu and Vss predictions for all classes. Among tissue composition parameters, changes in Kpu outputs were especially attributed to changes in tissue acidic phospholipid concentrations and extracellular protein tissue:plasma ratio values. In conclusion, this work demonstrates that for parameter estimation involving PBPK models and dimensionality reduction purposes, less influential parameters might be assigned fixed values depending on the parameter space, while influential parameters could be subject to parameters estimation.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 539
Typ av publikation
tidskriftsartikel (440)
forskningsöversikt (52)
doktorsavhandling (25)
bokkapitel (11)
konferensbidrag (7)
rapport (1)
visa fler...
annan publikation (1)
licentiatavhandling (1)
patent (1)
visa färre...
Typ av innehåll
refereegranskat (483)
övrigt vetenskapligt/konstnärligt (52)
populärvet., debatt m.m. (3)
Författare/redaktör
Svensson, Elin, 1985 ... (25)
Bergström, Christel, ... (24)
Lennernäs, Hans (21)
Nielsen, Jens B, 196 ... (19)
Artursson, Per (18)
Bergström, Christel ... (12)
visa fler...
Karlsson, Mats (11)
Wegler, Christine (11)
Uhlén, Mathias (10)
Simonsson, Ulrika S. ... (10)
Borén, Jan, 1963 (9)
Dahlgren, David (9)
Diacon, Andreas H. (8)
Sjögren, Erik, 1977- (8)
Teleki, Alexandra (8)
Dorlo, Thomas P C (8)
Larsson, Per (8)
Nandakumar, Kutty Se ... (8)
Friberg, Lena E (8)
Friberg, Lena (8)
Augustijns, Patrick (8)
Abrahamsson, Bertil (7)
Karlsson, Mats O. (7)
Frenning, Göran (7)
Hedeland, Mikael (7)
Kjellsson, Maria C., ... (7)
Jirstrand, Mats, 196 ... (7)
Syvänen, Stina (7)
Huitema, Alwin D R (7)
Beijnen, Jos H (7)
Sjöblom, Markus, 197 ... (7)
Erdelyi, Mate, 1975 (6)
Denti, Paolo (6)
Sunnerhagen, Per, 19 ... (6)
Darwich, Adam S. (6)
Abulfathi, Ahmed A. (6)
Mardinoglu, Adil, 19 ... (6)
Berg, Staffan (6)
Malmsten, Martin (6)
Turkez, H. (6)
Kabedev, Aleksei (6)
Mardinoglu, Adil (5)
Schiöth, Helgi B. (5)
Andersson, Tommy B. (5)
Turkez, Hasan (5)
Cardilin, Tim, 1989 (5)
Kälvemark Sporrong, ... (5)
Davies, Nigel (5)
Hesseling, Anneke C. (5)
Sou, Tomás (5)
visa färre...
Lärosäte
Uppsala universitet (304)
Chalmers tekniska högskola (79)
Göteborgs universitet (59)
Lunds universitet (44)
Kungliga Tekniska Högskolan (37)
Karolinska Institutet (27)
visa fler...
Linköpings universitet (23)
Stockholms universitet (18)
Umeå universitet (16)
Sveriges Lantbruksuniversitet (9)
Högskolan i Halmstad (8)
Malmö universitet (8)
Örebro universitet (6)
RISE (5)
Luleå tekniska universitet (4)
Högskolan i Skövde (2)
Linnéuniversitetet (1)
Högskolan i Borås (1)
Högskolan Dalarna (1)
Marie Cederschiöld högskola (1)
visa färre...
Språk
Engelska (537)
Svenska (1)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (539)
Naturvetenskap (104)
Teknik (23)
Lantbruksvetenskap (5)
Samhällsvetenskap (5)
Humaniora (2)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy