| 1. |
- Andersson, Jenny Marie, et al.
(författare)
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The plant dehydrin Lti30 stabilizes lipid lamellar structures in varying hydration conditions[S]
- 2020
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 61:7, s. 1014-1024
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge to plant growth and survival are changes in temperature and diminishing water supply. During acute temperature and water stress, plants often express stress proteins, such as dehydrins, which are intrinsically disordered hydrophilic proteins. In this article, we investigated how the dehydrin Lti30 fromArabidopsis thalianastabilizes membrane systems that are exposed to large changes in hydration. We also compared the effects of Lti30 on membranes with those of the simple osmolytes urea and trimethylamineN-oxide. Using X-ray diffraction and solid-state NMR, we studied lipid-protein self-assembly at varying hydration levels. We made the following observations:1) the association of Lti30 with anionic membranes relies on electrostatic attraction, and the protein is located in the bilayer interfacial membrane region;2) Lti30 can stabilize the lamellar multilayer structure, making it insensitive to variations in water content;3) in lipid systems with a composition similar to those present in some seeds and plants, dehydrin can prevent the formation of nonlamellar phases upon drying, which may be crucial for maintaining membrane integrity; and4) Lti30 stabilizes bilayer structures both at high and low water contents, whereas the small osmolyte molecules mainly prevent dehydration-induced transitions. These results corroborate the idea that dehydrins are part of a sensitive and multifaceted regulatory mechanism that protects plant cells against stress.
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| 2. |
- Björklund, Sebastian, et al.
(författare)
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The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier
- 2016
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 479, s. 207-220
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Tidskriftsartikel (refereegranskat)abstract
- In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol.
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| 3. |
- Duyen, Nguyen Thi, et al.
(författare)
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Steroid glycosides isolated from Paris polyphylla var. chinensis aerial parts and paris saponin II induces G1/S-phase MCF-7 cell cycle arrest
- 2022
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215. ; 519
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Tidskriftsartikel (refereegranskat)abstract
- In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic effects in vitro in the MCF-7 human cancer cell line. Here, we used combined chromatographic separations to isolate six compounds including a new steroid glycoside, paripoloside A (3), and five known compounds, from the butanol extract of the aerial parts of P. polyphylla. We unambiguously elucidated their structures based on spectroscopic data (proton and carbon-13 nuclear magnetic resonance, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, correlation spectroscopy, and high-resolution electrospray ionization mass spectroscopy data), and chemical reactions. Among the isolated compounds, paris saponin II (PSII) had the strongest cytotoxic effects against MCF-7 breast cancer cells. Interestingly, PSII significantly increased the expression of p53, p21, p27, and Bax protein levels and significantly suppressed the expression of cyclin D1 and retinoblastoma protein. These data suggest that PSII may induce G1/S phase cell cycle arrest and apoptosis pathway development in MCF-7 cells. Furthermore, the MCF-7 breast cancer cells mechanism of PSII was also investigated using molecular docking. Together, our results demonstrate that isolated compounds from P. polyphylla are promising candidates as breast cancer inhibitors.
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| 4. |
- Fridolf, Simon, et al.
(författare)
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Ganglioside GM3 stimulates lipid-protein co-assembly in α-synuclein amyloid formation
- 2023
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Ingår i: Biophysical Chemistry. - : Elsevier BV. - 0301-4622. ; 293
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease is characterized by the aggregation of the presynaptic protein α-synuclein (αSyn), and its co-assembly with lipids and other cellular matter in the brain. Here we investigated lipid-protein co-assembly in a system composed of αSyn and model membranes containing the glycolipid ganglioside GM3. We quantified the uptake of lipids into the co-assembled aggregates and investigated how lipid molecular dynamics is altered by being present in the co-assemblies using solution 1H- and solid-state 13C NMR spectroscopy. Aggregate morphology was studied using cryo-TEM. The overall lipid uptake in the co-assembled aggregates was found to increase with the molar ratio of GM3 in the vesicles. The lipids present in the co-assembled aggregates have reduced acyl chain and headgroup dynamics compared to the protein-free bilayer system. These findings may improve our understanding of how different types of lipids can influence the composition of αSyn aggregates, which may have consequences for amyloid formation in vivo.
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| 5. |
- Lin, Ruiyu, et al.
(författare)
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Kinetic Influence of Siliceous Reactions on Structure Formation of Mesoporous Silica Formed via the Co-Structure Directing Agent Route
- 2016
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 120:7, s. 3814-3821
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the mechanism responsible for the formation of mesoporous silica formed with the so-called costructure directing agent (CSDA) route. The synthesis relies on the interaction between silica source (tetraethylorthosilicate), cationic surfactant (C18H37N+(CH3)2(CH2)3N+(CH3)3Br2), and CSDA (carboxyethylsilanetriol), which results in a material functionalized with carboxylic groups. Depending on the concentration of HCl in the synthesis, the structure is defined by Fm3¯m (at high pH) and by Fd3¯m (at low pH), with a gradual transition in the intermediate pH range. Here, we aim at finding the origin for the structural change triggered by pH and investigate the effects of the hydrolysis of the silica source on the overall kinetics of the synthesis. A fast process results in Fm3¯m, regardless of pH, and a slow process results in Fd3¯m. The hydrolysis step is the important structural control parameter. We studied the cross-linking of silica and CSDA using 29Si NMR. The cross-linking is similar for the two structures, and possibly the Fd3¯m structure contains slightly more CSDA. 13C PT ssNMR was used to investigate the surfactant mobility/rigidity during the synthesis. The rigidity of the Fm3¯m is established much faster than that of the Fd3¯m.
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| 6. |
- Mojumdar, Enamul Haque, et al.
(författare)
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Skin hydration : Interplay between molecular dynamics, structure and water uptake in the stratum corneum
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Hydration is a key aspect of the skin that influences its physical and mechanical properties. Here, we investigate the interplay between molecular and macroscopic properties of the outer skin layer - the stratum corneum (SC) and how this varies with hydration. It is shown that hydration leads to changes in the molecular arrangement of the peptides in the keratin filaments as well as dynamics of C-H bond reorientation of amino acids in the protruding terminals of keratin protein within the SC. The changes in molecular structure and dynamics occur at a threshold hydration corresponding to ca. 85% relative humidity (RH). The abrupt changes in SC molecular properties coincide with changes in SC macroscopic swelling properties as well as mechanical properties in the SC. The flexible terminals at the solid keratin filaments can be compared to flexible polymer brushes in colloidal systems, creating long-range repulsion and extensive swelling in water. We further show that the addition of urea to the SC at reduced RH leads to similar molecular and macroscopic responses as the increase in RH for SC without urea. The findings provide new molecular insights to deepen the understanding of how intermediate filament organization responds to changes in the surrounding environment.
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| 7. |
- Pham, Quoc Dat, et al.
(författare)
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Chemical penetration enhancers in stratum corneum : Relation between molecular effects and barrier function
- 2016
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 232, s. 175-187
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Tidskriftsartikel (refereegranskat)abstract
- Skin is attractive for drug therapy because it offers an easily accessible route without first-pass metabolism. Transdermal drug delivery is also associated with high patient compliance and through the site of application, the drug delivery can be locally directed. However, to succeed with transdermal drug delivery it is often required to overcome the low permeability of the upper layer of the skin, the stratum corneum (SC). One common strategy is to employ so-called penetration enhancers that supposedly act to increase the drug passage across SC. Still, there is a lack of understanding of the molecular effects of so-called penetration enhancers on the skin barrier membrane, the SC. In this study, we provide a molecular characterization of how different classes of compounds, suggested as penetration enhancers, influence lipid and protein components in SC. The compounds investigated include monoterpenes, fatty acids, osmolytes, surfactant, and Azone. We employ natural abundance C-13 polarization transfer solid-state nuclear magnetic resonance (NMR) on intact porcine SC. With this method it is possible to detect small changes in the mobility of the minor fluid lipid and protein SC components, and simultaneously obtain information on the major fraction of solid SC components. The balance between fluid and solid components in the SC is essential to determine macroscopic material properties of the SC, including barrier and mechanical properties. We study SC at different hydration levels corresponding to SC in ambient air and under occlusion. The NMR studies are complemented with diffusion cell experiments that provide quantitative data on skin permeability when treated with different compounds. By correlating the effects on SC molecular components and SC barrier function, we aim at deepened understanding of diffusional transport in SC, and how this can be controlled, which can be utilized for optimal design of transdermal drug delivery formulations. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.
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| 8. |
- Pham, Quoc Dat
(författare)
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Foreign molecules in biomembranes : Molecular effects on intact stratum corneum and model lipid systems
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis mainly explores how the molecular mobility of lipid and protein components in the outermost layer of the skin, the stratum corneum (SC), varies with different conditions and upon adding foreign compounds. These studies require methods that makes it possible to detect and characterize the minor amount of fluid components in the highly ordered solid SC sample with resolved molecular information. 13C polarization transfer solid-state nuclear magnetic resonance (PT ssNMR) is well suited for this task, and was employed as the main method through this thesis. The aims of this thesis were achieved by studies on well-controlled systems of intact SC, extracted corneocyte, and model lipid systems, and by combining PT ssNMR with different complementary biophysical techniques.A general conclusion from the presented studies of different foreign compounds is that apolar compounds mainly affect SC lipids, while more polar compounds affect both SC lipid and protein components. The effects strongly depend on the identity of the additive, and on the hydration conditions, and they vary with concentrations and temperatures. One interesting finding is the essential role of water in the mobility of keratin filaments. Apart from the effects on SC components, one can also simultaneously characterize the molecular mobility of the additves that are incorporated in the complex SC matrix by using PT ssNMR.We also demonstrate a clear correlation between the molecular mobility in SC lipids and proteins and the skin permeability upon additives, which forwards the understanding of the skin macroscopic barrier function at a molecular level. The findings of this research can be applied in topical formulations for, e.g., drug delivery and skin care products.
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| 9. |
- Pham, Quoc Dat, et al.
(författare)
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Mucoadhesion : mucin-polymer molecular interactions
- 2021
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173. ; 610
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Tidskriftsartikel (refereegranskat)abstract
- Mucoadhesion, adhesion of a material to a mucous membrane or a mucus-covered surface, has been employed in drug delivery to prolong contact with adsorption sites and consequently a likely improvement of drug absorption. Mucoadhesion in the oral cavity also provides additional effects on tactile mouthfeel and extended flavor delivery, which impact consumer perception. The mechanisms behind mucoadhesion have not been well understood and there are contradictory literature results on the ranking of mucoadhesive properties of different polymers based on what in-vitro methods that are used. We herein examine the molecular interactions of different polymers with mucin from bovine submaxillary glands at pH 6.6 by using 1H NMR (Nuclear Magnetic Resonance) that provides atomically resolved information on conformational mobility of the mucin. Studying different types of polymers with different chemical structures and degrees of polymerization (DP), we can via the NMR linewidths and the signal intensities distinguish if the polymers interact with specific segments of the mucin or if they have a universal effect on the mobility of all the molecular segments of the mucin. The specific interaction sites on the mucin for positively charged polymer poly(ethyleneimine) are shown to be different from those for negatively and neutrally charged polymers. In addition, the interactions are also driven by the DP, the concentration of the polymers, and the dehydration. Deepened understanding of molecular effects of the different polymers on the mucin can therefore have strong impact on the development of mucoadhesive products in pharmaceutical and food applications. Finally, we raise awareness of the interpretation of rheological data in terms of mucoadhesion.
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| 10. |
- Pham, Quoc Dat, et al.
(författare)
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Quantification of the amount of mobile components in intact stratum corneum with natural-abundance 13C solid-state NMR
- 2020
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Ingår i: Physical chemistry chemical physics : PCCP. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 22:12, s. 6572-6583
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Tidskriftsartikel (refereegranskat)abstract
- The outermost layer of the skin is the stratum corneum (SC), which is mainly comprised of solid proteins and lipids. Minor amounts of mobile proteins and lipids are crucial for the macroscopic properties of the SC, including softness, elasticity and barrier function. Still this minor number of mobile components are not well characterized in terms of structure or amount. Conventional quantitative direct polarization (Q-DP) 13C solid-state NMR gives signal amplitudes proportional to concentrations, but fails to quantify the SC mobile components because of spectral overlap with the overwhelming signals from the solids. Spectral editing with the INEPT scheme suppresses the signals from solids, but also modulates the amplitudes of the mobile components depending on their values of the transverse relaxation times T2, scalar couplings JCH, and number of covalently bound hydrogens nH. This study describes a quantitative INEPT (Q-INEPT) method relying on systematic variation of the INEPT timing variables to estimate T2, JCH, nH, and amplitude for each of the resolved resonances from the mobile components. Q-INEPT is validated with a series of model systems containing molecules with different hydrophobicity and dynamics. For selected systems where Q-DP is applicable, the results of Q-INEPT and Q-DP are similar with respect to the linearity and uncertainty of the obtained molar ratios. Utilizing a reference compound with known concentration, we quantify the concentrations of mobile lipids and proteins within the mainly solid SC. By melting all lipids at high temperature, we obtain the total lipid concentration. These Q-INEPT results are the first steps towards a quantitative understanding of the relations between mobile component concentrations and SC macroscopic properties.
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