| 1. |
- Hojjat-Farsangi, Mohammad
(författare)
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Small-molecule inhibitors of the receptor tyrosine kinases : promising tools for targeted cancer therapies
- 2014
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Ingår i: International Journal of Molecular Sciences. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1422-0067.
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK–TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK–TKIs have been developed for the treatment of cancer patients. Specific/selective RTK–TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK–TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.
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| 2. |
- Barrozo, Alexandre, et al.
(författare)
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Computational Protein Engineering: Bridging the Gap between Rational Design and Laboratory Evolution
- 2012
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 13:10, s. 12428-12460
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Forskningsöversikt (refereegranskat)abstract
- Enzymes are tremendously proficient catalysts, which can be used as extracellular catalysts for a whole host of processes, from chemical synthesis to the generation of novel biofuels. For them to be more amenable to the needs of biotechnology, however, it is often necessary to be able to manipulate their physico-chemical properties in an efficient and streamlined manner, and, ideally, to be able to train them to catalyze completely new reactions. Recent years have seen an explosion of interest in different approaches to achieve this, both in the laboratory, and in silico. There remains, however, a gap between current approaches to computational enzyme design, which have primarily focused on the early stages of the design process, and laboratory evolution, which is an extremely powerful tool for enzyme redesign, but will always be limited by the vastness of sequence space combined with the low frequency for desirable mutations. This review discusses different approaches towards computational enzyme design and demonstrates how combining newly developed screening approaches that can rapidly predict potential mutation “hotspots” with approaches that can quantitatively and reliably dissect the catalytic step can bridge the gap that currently exists between computational enzyme design and laboratory evolution studies.
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| 3. |
- Blom, Hans, et al.
(författare)
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Electrostatic Interactions of Fluorescent Molecules with Dielectric Interfaces Studied by Total Internal Reflection Fluorescence Correlation Spectroscopy
- 2010
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 11:2, s. 368-406
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Tidskriftsartikel (refereegranskat)abstract
- Electrostatic interactions between dielectric surfaces and different fluorophoresused in ultrasensitive fluorescence microscopy are investigated using objective-based TotalInternal Reflection Fluorescence Correlation Spectroscopy (TIR-FCS). The interfacialdynamics of cationic rhodamine 123 and rhodamine 6G, anionic/dianionic fluorescein,zwitterionic rhodamine 110 and neutral ATTO 488 are monitored at various ionic strengthsat physiological pH. As analyzed by means of the amplitude and time-evolution of theautocorrelation function, the fluorescent molecules experience electrostatic attraction orrepulsion at the glass surface depending on their charges. Influences of the electrostaticinteractions are also monitored through the triplet-state population and triplet relaxationtime, including the amount of detected fluorescence or the count-rate-per-moleculeparameter. These TIR-FCS results provide an increased understanding of how fluorophoresare influenced by the microenvironment of a glass surface, and show a promising approachfor characterizing electrostatic interactions at interfaces.
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| 4. |
- Fuvesi, J., et al.
(författare)
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Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis
- 2012
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 13:6, s. 7676-7693
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Tidskriftsartikel (refereegranskat)abstract
- Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient's death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject.
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| 5. |
- Marcotuli, Ilaria, et al.
(författare)
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Non-Starch Polysaccharides in Durum Wheat : A Review
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:8, s. 2933-
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Tidskriftsartikel (refereegranskat)abstract
- Durum wheat is one of most important cereal crops that serves as a staple dietary component for humans and domestic animals. It provides antioxidants, proteins, minerals and dietary fibre, which have beneficial properties for humans, especially as related to the health of gut microbiota. Dietary fibre is defined as carbohydrate polymers that are non-digestible in the small intestine. However, this dietary component can be digested by microorganisms in the large intestine and imparts physiological benefits at daily intake levels of 30–35 g. Dietary fibre in cereal grains largely comprises cell wall polymers and includes insoluble (cellulose, part of the hemicellulose component and lignin) and soluble (arabinoxylans and (1,3;1,4)-β-glucans) fibre. More specifically, certain components provide immunomodulatory and cholesterol lowering activity, faecal bulking effects, enhanced absorption of certain minerals, prebiotic effects and, through these effects, reduce the risk of type II diabetes, cardiovascular disease and colorectal cancer. Thus, dietary fibre is attracting increasing interest from cereal processors, producers and consumers. Compared with other components of the durum wheat grain, fibre components have not been studied extensively. Here, we have summarised the current status of knowledge on the genetic control of arabinoxylan and (1,3;1,4)-β-glucan synthesis and accumulation in durum wheat grain. Indeed, the recent results obtained in durum wheat open the way for the improvement of these important cereal quality parameters.
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| 6. |
- Sommertune, Jens, et al.
(författare)
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Polymer/iron oxide nanoparticle composites—A straight forward and scalable synthesis approach
- 2015
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 16:8, s. 19752-19768
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic nanoparticle systems can be divided into single-core nanoparticles (with only one magnetic core per particle) and magnetic multi-core nanoparticles (with several magnetic cores per particle). Here, we report multi-core nanoparticle synthesis based on a controlled precipitation process within a well-defined oil in water emulsion to trap the superparamagnetic iron oxide nanoparticles (SPION) in a range of polymer matrices of choice, such as poly(styrene), poly(lactid acid), poly(methyl methacrylate), and poly(caprolactone). Multi-core particles were obtained within the Z-average size range of 130 to 340 nm. With the aim to combine the fast room temperature magnetic relaxation of small individual cores with high magnetization of the ensemble of SPIONs, we used small (<10 nm) core nanoparticles. The performed synthesis is highly flexible with respect to the choice of polymer and SPION loading and gives rise to multi-core particles with interesting magnetic properties and magnetic resonance imaging (MRI) contrast efficacy.
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| 7. |
- Mohsenzadeh, Abas, et al.
(författare)
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The Effect of Carbon Monoxide Co-Adsorption on Ni-Catalysed Water Dissociation
- 2013
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Ingår i: International Journal of Molecular Sciences. - : M D P I AG. - 1661-6596 .- 1422-0067. ; 14:12, s. 23301-23314
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Tidskriftsartikel (refereegranskat)abstract
- The effect of carbon monoxide (CO) co-adsorption on the dissociation of water on the Ni(111) surface has been studied using density functional theory. The structures of the adsorbed water molecule and of the transition state are changed by the presence of the CO molecule. The water O–H bond that is closest to the CO is lengthened compared to the structure in the absence of the CO, and the breaking O–H bond in the transition state structure has a larger imaginary frequency in the presence of CO. In addition, the distances between the Ni surface and H2O reactant and OH and H products decrease in the presence of the CO. The changes in structures and vibrational frequencies lead to a reaction energy that is 0.17 eV less exothermic in the presence of the CO, and an activation barrier that is 0.12 eV larger in the presence of the CO. At 463 K the water dissociation rate constant is an order of magnitude smaller in the presence of the CO. This reveals that far fewer water molecules will dissociate in the presence of CO under reaction conditions that are typical for the water-gas-shift reaction.
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| 8. |
- Taherzadeh, M.J., et al.
(författare)
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Pretreatment of lignocellulosic wastes to improve ethanol and biogas production : A review
- 2008
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Ingår i: International Journal of Molecular Sciences. - : Molecular Diversity Preservation International (MDPI) AG.. - 1661-6596 .- 1422-0067. ; 9:9, s. 1621-1651
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Tidskriftsartikel (refereegranskat)abstract
- Lignocelluloses are often a major or sometimes the sole components of different waste streams from various industries, forestry, agriculture and municipalities. Hydrolysis of these materials is the first step for either digestion to biogas (methane) or fermentation to ethanol. However, enzymatic hydrolysis of lignocelluloses with no pretreatment is usually not so effective because of high stability of the materials to enzymatic or bacterial attacks. The present work is dedicated to reviewing the methods that have been studied for pretreatment of lignocellulosic wastes for conversion to ethanol or biogas. Effective parameters in pretreatment of lignocelluloses, such as crystallinity, accessible surface area, and protection by lignin and hemicellulose are described first. Then, several pretreatment methods are discussed and their effects on improvement in ethanol and/or biogas production are described. They include milling, irradiation, microwave, steam explosion, ammonia fiber explosion (AFEX), supercritical CO2 and its explosion, alkaline hydrolysis, liquid hot-water pretreatment, organosolv processes, wet oxidation, ozonolysis, dilute- and concentrated-acid hydrolyses, and biological pretreatments.
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| 9. |
- Fontes, Magnus
(författare)
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Optimal results for the nonhomogeneous initial-boundary value problem for the two-dimensional Navier-Stokes equations
- 2010
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Ingår i: Journal of Mathematical Fluid Mechanics. - : Springer Science and Business Media LLC. - 1422-6928 .- 1422-6952. ; 12, s. 412-434
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Tidskriftsartikel (refereegranskat)abstract
- In this work we study the fully nonhomogeneous initial boundary value problem for the two-dimensional time-dependent Navier–Stokes equations in a general open space domain in R2 with low regularity assumptions on the initial and the boundary value data. We show that the perturbed Navier–Stokes operator is a diffeomorphism from a suitable function space onto its own dual and as a corollary we get that the Navier–Stokes equations are uniquely solvable in these spaces and that the solution depends smoothly on all involved data. Our source data space and solution space are in complete natural duality and in this sense, without any smallness assumptions on the data, we solve the equations for data with optimally low regularity in both space and time.
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| 10. |
- Han, Yilin, et al.
(författare)
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Towards 3D Bioprinted Spinal Cord Organoids
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:10
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional (3D) cultures, so-called organoids, have emerged as an attractive tool for disease modeling and therapeutic innovations. Here, we aim to determine if boundary cap neural crest stem cells (BC) can survive and differentiate in gelatin-based 3D bioprinted bioink scaffolds in order to establish an enabling technology for the fabrication of spinal cord organoids on a chip. BC previously demonstrated the ability to support survival and differentiation of co-implanted or co-cultured cells and supported motor neuron survival in excitotoxically challenged spinal cord slice cultures. We tested different combinations of bioink and cross-linked material, analyzed the survival of BC on the surface and inside the scaffolds, and then tested if human iPSC-derived neural cells (motor neuron precursors and astrocytes) can be printed with the same protocol, which was developed for BC. We showed that this protocol is applicable for human cells. Neural differentiation was more prominent in the peripheral compared to central parts of the printed construct, presumably because of easier access to differentiation-promoting factors in the medium. These findings show that the gelatin-based and enzymatically cross-linked hydrogel is a suitable bioink for building a multicellular, bioprinted spinal cord organoid, but that further measures are still required to achieve uniform neural differentiation.
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