| 1. |
- Bjorklund, Geir, et al.
(författare)
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Metals and Parkinson's Disease : Mechanisms and Biochemical Processes
- 2018
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 25:19, s. 2198-2214
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Forskningsöversikt (refereegranskat)abstract
- Genetic background accounts for only 5 to 10% of the reported cases of Parkinson's disease (PD), while the remaining cases are of unknown etiology. It is believed that environmental factors may be involved in the causality of a large proportion of PD cases. Several PD genes are activated by xenobiotic exposure, and a link between pesticide exposure and PD has been demonstrated. Many epidemiological studies have shown an association between PD and exposure to metals such as mercury, lead, manganese, copper, iron, aluminum, bismuth, thallium, and zinc. This review explores the biological effects, the pathogenetic processes, genetic susceptibilities to metals as well as examining future strategies for PD treatment, such as chelation therapy.
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| 2. |
- El-Seedi, Hesham R., et al.
(författare)
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Naturally Occurring Xanthones; Biological Activities, Chemical Profiles and In Silico Drug Discovery
- 2024
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 31:1, s. 62-101
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Forskningsöversikt (refereegranskat)abstract
- Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon & PRIME;s isolated compounds from 2017-2020. We found that only a-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 M-pro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 M-pro with docking scores of -11.2 and -11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the M-pro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.
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| 3. |
- El-Seedi, Hesham R., et al.
(författare)
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Naturally occurring xanthones; latest investigations : isolation, structure elucidation and chemosystematic significance
- 2009
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 16:20, s. 2581-2626
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Forskningsöversikt (refereegranskat)abstract
- In this review, an updated literature survey covering the reports of naturally occurring xanthones in the period of 2005-2008 is presented. In some 143 studies, the isolation of 264 different xanthones from 36 plant species (representing 15 genera in 6 families of higher plants), 7 species of fungi, and 1 lichen species were reported. Of these, 122 compounds were isolated for the first time from nature. We discuss plant origin, the way of separation, and spectral analysis done for structure elucidation, along with a brief discussion of the chemosystematic significance.
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| 4. |
- El-Seedi, Hesham R., et al.
(författare)
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Recent insights into the biosynthesis and biological activities of natural xanthones
- 2010
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:9, s. 854-901
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Forskningsöversikt (refereegranskat)abstract
- This review focuses on recent advances in our understanding of the complex biosynthetic pathways and diverse biological activities of naturally occurring xanthones. The biosynthesis section covers studies published from 1989 to 2008 on xanthone production in plants and fungi, while the bioactivity review presents tabulated activities of more than 250 xanthones described in studies published from 2001 to 2008, together with structural information and indications of their wide-ranging potential uses as pharmacological tools. A large number of relevant papers have been published on these subjects (128 cited here), illustrating the diversity of the xanthones and their possible uses.
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| 5. |
- Eriksson, Staffan
(författare)
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Is the Expression of Deoxynucleoside Kinases and 5 '-nucleotidases in Animal Tissues Related to the Biological Effects of Nucleoside Analogs?
- 2013
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 20, s. 4241-4248
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Tidskriftsartikel (refereegranskat)abstract
- Nucleoside analogs serve as important chemotherapeutic agents in a number of severe diseases such as cancer and viral infections. These agents are pro-drugs that have to be taken up and phosphorylated in several steps to be trapped in the cells and transformed to active metabolites that inhibit essential steps in the replication of viruses or malignant cells. The anabolic deoxynucleoside kinases (dNKs) and catabolic 5'- nucleotidases(5'-NTs) are involved in maintaining substrate cycles, and act as regulators for the intracellular pools of active nucleotide metabolites. In this chapter the expression patterns of the four dNKs i.e. cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) and the mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) as well as the six intracellular 5'-NTs: cN-IA, cN-IB, cN-II, cN-III, cdN, mdN, present in animal cells and tissues will be described. Their role as primary controllers of the accumulation and activation of important anti viral and anti cancer nucleoside analogs in different tissues involved in the pathophysiology of these diseases will be evaluated. The predictability of using the ratios between the activities of the dNKs and 5'-NTs for estimating efficacy and side effects of nucleoside drug candidates will be discussed as well as recommendations on how to use this information to improve future therapies with nucleoside drugs.
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| 6. |
- Ernerudh, Jan, 1952-, et al.
(författare)
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The use of cell products for treatment of autoimmune neuroinflammatory diseases
- 2002
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Ingår i: Current Medicinal Chemistry. - 0929-8673 .- 1875-533X. ; 9:16, s. 1497-1505
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Tidskriftsartikel (refereegranskat)abstract
- Cell products are live cells that are given to patients in order to replace or modify the function of missing or dysfunctional cells. Progress in technology and in the understanding of pathobiology may lead to the use of cell products in many areas. This review outlines the use of cell products in the treatment of autoimmune diseases, with focus on neuroinflammatory diseases like multiple sclerosis. Treatment of autoimmune diseases should be selective and specific in order to avoid serious side effects. To achieve this, T lymphocyte regulation has been in focus for several immunomodulatory regimens. One area of great interest is the use of T cell vaccination, when autologous attenuated auto-reactive T cells are given to patients in order to initiate a specific immune response to the pathogenic T cell populations. Phopheresis may be an immunomudulatory treatment related to T cell vaccination. Another promising area involves ex-vivo alteration of the cytokine profile of harmful auto-reactive T cells. This can be achieved by genetic manipulation or by certain cytokine stimulations. A subsequent adoptive cell transfer will, by homing mechanisms, lead to at site specific delivery of the cells, which will have a local down-regulatory effect on the inflammatory process. Although unsolved questions regarding doses, timing, optimal preparing conditions and mechanisms still remain, both T cell vaccination and adoptive transfer of ex-vivo manipulated cytokine secreting cells have proven successful for treatment of neuroinflammation in experimental models. T cell vaccination was shown to be feasible in patients with multiple sclerosis, however, otherwise the experience in humans so far is limited.
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| 7. |
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| 8. |
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| 9. |
- Gurevich-Panigrahi, Tatiana, et al.
(författare)
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Obesity : Pathophysiology and Clinical
- 2009
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Ingår i: Current Medicinal Chemistry. - : Bentham Science. - 0929-8673 .- 1875-533X. ; 16:4, s. 506-521
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is an increasingly serious socioeconomic and clinical problem. Between 1/4 - 1/3 of population in the developed countries can be classified as obese. Four major etiological factors for development of obesity are genetic determinants, environmental factors, food intake and exercise. Obesity increases the risk of the development of various pathologic conditions including: insulin-resistant diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, endocrine problems, and certain forms of cancer. Thus, obesity is a negative determinant for longevity. In this review we provide broad overview of pathophysiology of obesity. We also discuss various available, and experimental therapeutic methods. We highlight functions of adipocytes including fat storing capacity and secretory activity resulting in numerous endocrine effects like leptin, IL-6, adiponectin, and resistin. The anti-obesity drugs are classified according to their primary action on energy balance. Major classes of these drugs are: appetite suppressants, inhibitors of fat absorption (i.e. orlistat), stimulators of thermogenesis and stimulators of fat mobilization. The appetite suppressants are further divided into noradrenergic agents, (i.e. phentermine, phendimetrazine, benzphetamine, diethylpropion), serotoninergic agents (i.e. dexfenfluramine), and mixed noradrenergic-serotoninergic agents (i.e. sibutramine). Thus, we highlight recent advances in the understanding of the central neural control of energy balance, current treatment strategies for obesity and the most promising targets for the development of novel anti-obesity drugs.
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| 10. |
- Johnston, James B., et al.
(författare)
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Targeting the EGFR pathway for cancer therapy
- 2006
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 13:29, s. 3483-3492
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally, in most patients with multiple myeloma, the malignant cells over-express a number of epidermal growth factor receptors (EGFR)s and their ligands, HB-EGF and amphiregulin, thus this growth-factor family may be an important aspect in the patho-biology of this disease. These and other, related findings have provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, Z131839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e.g.: Trastuzumab / Herceptin, Pertuzumab / Omnitarg / rhuMab-2C4, Cetuximab / Erbitux / IMC-C225, Panitumumab / Abenix / ABX-EGF, and also ZD6474). In addition, we summarize, both current therapy development driven by antibody-based targeting of the EGFR-dependent signaling pathways, and furthermore, we provide a background on the history and the development of therapeutic antibodies.
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| 11. |
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| 12. |
- Kumar, Saroj, et al.
(författare)
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Role of Infrared Spectroscopy and Imaging in Cancer Diagnosis
- 2018
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Ingår i: Current Medicinal Chemistry. - : BENTHAM SCIENCE PUBL LTD. - 0929-8673 .- 1875-533X. ; 25:9, s. 1055-1072
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Forskningsöversikt (refereegranskat)abstract
- Background: Cancer is a major global health issue. It causes extensive individual suffering and gives a huge burden on the health care in society. Despite extensive research and different tools have been developed it still remains a challenge for early detection of this disease. FTIR imaging has been used to diagnose and differentiate the molecular differences between normal and diseased tissues. Methods: Fourier Transform Infrared Spectroscopy (FTIR) is able to measure biochemical changes in tissue, cell and biofluids based on the vibrational signature of their components. This technique enables to the distribution and structure of lipids, proteins, nucleic acids as well as other metabolites. These differences depended on the type and the grade of cancer. Results: We emphasize here, that the FTIR spectroscopy and imaging can be considered as a promising technique and will find its place on the detection of this dreadful disease because of high sensitivity, accuracy and inexpensive technique. Now the medical community started using and accepting this technique for early stage cancer detection. We discussed this technique and the several challenges in its application for the diagnosis of cancer in regards of sample preparations, data interpretation, and data analysis. The sensitivity of chemotherapy drugs on individual specific has also discussed. Conclusion: So far progressed has done with the FTIR imaging in understanding of cancer disease pathology. However, more research is needed in this field and it is necessary to understand the morphology and biology of the sample before using the spectroscopy and imaging because invaluable information to be figured out.
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| 13. |
- Labropoulou, V. T., et al.
(författare)
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Pathophysiology and Pharmacological Targeting of Tumor-Induced Bone Disease : Current Status and Emerging Therapeutic Interventions
- 2011
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Ingår i: Current Medicinal Chemistry. - 0929-8673 .- 1875-533X. ; 18:11, s. 1584-1598
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Forskningsöversikt (refereegranskat)abstract
- Bone disease is a common complication of metastatic solid tumors but also of primary hematological malignancies such as multiple myeloma. Our understanding of the molecular mechanisms underlying the development of bone disease by solid tumors and multiple myeloma has been significantly improved. A complex inter-dependence exists between bone disease and malignant cell growth, creating a vicious cycle of extensive bone destruction and tumor progression. Although myeloma and solid tumors share a number of common molecular pathogenetic mechanisms, they involve distinct pathophysiological pathways, resulting in osteoclastic bone resorption and inhibition of bone formation. In this review, we analyze the molecular mechanisms, involved in tumor-induced bone disease and discuss the current therapeutic approaches and the most recent clinical developments of emerging targeted therapies.
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| 14. |
- Lehtimäki, Lauri, et al.
(författare)
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Clinical Values of Nitric Oxide Parameters from the Respiratory System
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:42, s. 7189-7199
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Fractional exhaled nitric oxide (FENO) concentration reliably reflects central airway inflammation, but it is not sensitive to changes in the NO dynamics in the lung periphery. By measuring FENO at several different flow rates one can estimate alveolar NO concentration (CANO), bronchial NO flux (JawNO), bronchial wall NO concentration (CawNO) and the bronchial diffusivity of NO (DawNO).OBJECTIVE: We aimed to describe the current knowledge and clinical relevance of NO parameters in different pulmonary diseases.METHODS: We conducted a systematic literature search to identify publications reporting NO parameters in subjects with pulmonary or systemic diseases affecting the respiratory tract. A narrative review was created for those with clinical relevance.RESULTS: Estimation of pulmonary NO parameters allows for differentiation between central and peripheral inflammation and a more precise analysis of central airway NO output. CANO seems to be a promising marker of parenchymal inflammation in interstitial lung diseases and also a marker of tissue damage and altered gas diffusion in chronic obstructive pulmonary disease and systemic diseases affecting the lung. In asthma, CANO can detect small airway involvement left undetected by ordinary FENO measurement. Additionally, CawNO and DawNO can be used in asthma to assess if FENO is increased due to enhanced inflammatory activity (increased CawNO) or tissue changes related to bronchial remodelling (altered DawNO).CONCLUSION: NO parameters may be useful for diagnosis, prediction of disease progression and prediction of treatment responses in different parenchymal lung and airway diseases. Formal trials to test the added clinical value of NO parameters are needed.
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| 15. |
- Lendvai, Gabor, et al.
(författare)
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Radiolabelled Oligonucleotides for Imaging of Gene Expression with PET
- 2009
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 16:33, s. 4445-4461
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Forskningsöversikt (refereegranskat)abstract
- Our understanding of altered patterns of gene expression being responsible for many diseases has been growing thanks to modern molecular biological methods. Today, these changes can only be identified when tissue samples are available. Therefore, a noninvasive method allowing us to monitor gene expression in vivo would be valuable, not only as a research tool, but also for patient stratification before treatment and for treatment follow-up. Antisense oligonucleotides (ODN) have been considered to be suitable molecules to trace active genes in vivo, as well as to treat diseases by hybridising to its complementary messenger RNA (mRNA) sequence in the cells thereby preventing the synthesis of the peptide. However, the use of ODNs in the organisms are endangered by many hurdles such as physical barriers to pass and enzyme attack to be avoided. Positron emission tomography (PET) provides a most advanced in vivo imaging technology that allows the exploration of the fate of radionuclide-labelled antisense ODNs in the body; thereby providing information about biodistribution and quantitative accumulation in tissues to assess pharmacokinetic properties of ODNs. This kind of evaluation is important as part of the characterisation of antisense therapeutics but also as part of the development of antisense imaging agents. This review provides a general summary about the antisense concept and displays the present status of the antisense imaging field with the major achievements and remaining challenges on the long journey towards accomplishing in vivo monitoring of gene expression using PET.
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| 16. |
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| 17. |
- Linusson, Anna, et al.
(författare)
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Statistical molecular design of balanced compound libraries for QSAR modeling
- 2010
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:19, s. 2001-2016
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Forskningsöversikt (refereegranskat)abstract
- A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.
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| 18. |
- Liu, Shan, et al.
(författare)
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Recent Progress on the Synthesis and Biomedical Properties of Natural Biopolymer Composites
- 2021
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers. - 0929-8673 .- 1875-533X. ; 28:40, s. 8243-8266
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Forskningsöversikt (refereegranskat)abstract
- Background: Natural biopolymers have drawn extensive attention because of their great biocompatibility, biodegradability, renewability, and the availability of various reactive functional groups for modifying and introducing novel components. In the last few years, numerous natural biopolymer composites have been exploited to improve their physical and chemical properties and add new functionalities.Methods: Herein, we summarize the current progress in three common classes of natural biopolymer-based composites, including alginate, chitosan, and gelatin.Results: The morphology characteristics, preparation methods, and unique functionalities of these biopolymer composites are also analyzed and discussed.Conclusion: Finally, the article offers an overview of recent progress in the main biomedical applications such as tissue engineering, wound-healing, and drug delivery, which inspires further progress in biopolymer composites with tailored mechanical property and stable characteristics for pharmaceutical and biomedical applications.
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| 19. |
- Malm, Johan, et al.
(författare)
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Thyroid Hormone Antagonists : Potential Medical Applications and Structure Activity Relationships
- 2009
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 16:25, s. 3258-3266
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Forskningsöversikt (refereegranskat)abstract
- Thyroid hormone receptors (TRs) exert profound effects on development, metabolism, and multiple specific organ functions. Principally by regulating crucial genes in a variety of tissues, the thyroid hormones, 3,5,3'-triiodo-L-thyronine (L-T-3, 1) and 3,5,3',5'-tetraiodo-L-thyronine (L-T-4, 2), influence basal calorigenesis and oxygen consumption, cardiac rate and contractility, lipid metabolism, bone structure and strength, and central nervous system functions critical for normal mentation and mood. Elevated levels of circulating and tissue 1 and/or 2 result in the thyrotoxic clinical state, manifested by weight loss despite increased caloric intake; heat intolerance due to increased calorigenesis; cardiac tachyarrhythmias, systolic hypertension, and heart failure; skeletal muscle weakness; and a spectrum of neuropsychiatric symptoms ranging from anxiety to delirium and psychosis. The current standard treatments of endogenous hyperthyroidism causing thyrotoxicosis reduce the overproduction of thyroid hormones by pharmacologically inhibiting their synthesis or release (e.g., with thionamides or lithium, respectively), or by ablating thyroid tissue surgically or with radioiodine. TR-antagonists could hypothetically have significant clinical use in treating thyrotoxic states if they were capable of promptly and completely restoring euthyroid levels of thyroid-specific gene activity. No TR alpha-selective ligands have been prepared up to this date, ligands that potentially would further ameliorate the problem with cardiac disease connected with hyperthyroidism and maybe cardiac arrhythmia. Despite its significant potential use, no TR-antagonist has reached clinical application. Design of TR-antagonists ligands has been based on the attachment of a large extension group at the 5-prime position of 1 or other structurally related analogues. This extension is believed to distort folding of the C-terminal helix ( helix 12) to the body of the ligand binding domain (LBD), which normally forms a coactivator site. Examples of synthetic TR antagonists based on this extension strategy are reviewed, as well as other strategies to achieve functional TR-antagonism.
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| 20. |
- Mitran, Bogdan, et al.
(författare)
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Radiolabeled GRPR Antagonists for Imaging of Disseminated Prostate Cancer : Influence of Labeling Chemistry on Targeting Properties
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:41, s. 7090-7111
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Radionuclide molecular imaging of gastrin-releasing peptide receptor (GRPR) expression promises unparalleled opportunities for visualizing subtle prostate tumors, which due to small size, adjacent benign tissue, or a challenging location would otherwise remain undetected by conventional imaging. Achieving high imaging contrast is essential for this purpose and the molecular design of any probe for molecular imaging of prostate cancer should be aimed at obtaining as high tumor-to-organ ratios as possible.OBJECTIVE: This short review summarizes the key imaging modalities currently used in prostate cancer, with a special focus on radionuclide molecular imaging. Emphasis is laid mainly on the issue of radiometals labeling chemistry and its influence on the targeting properties and biodistribution of radiolabeled GRPR antagonists for imaging of disseminated prostate cancer.METHODS: A comprehensive literature search of the PubMed/MEDLINE, and Scopus library databases was conducted to find relevant articles.RESULTS: The combination of radionuclide, chelator and required labeling chemistry was shown to have a significant influence on the stability, binding affinity, and internalization rate, off-target interaction with normal tissues and blood proteins, interaction with enzymes, activity uptake and retention in excretory organs and activity uptake in tumors of radiolabeled bombesin antagonistic analogues.CONCLUSION: Labeling chemistry had a very strong impact on the biodistribution profile of GRPR-targeting peptide based imaging probes and needs to be considered when designing a targeting probe for high contrast molecular imaging. Taking into account the complexity of in vivo interactions, it is not currently possible to accurately predict the optimal labeling approach. Therefore, a detailed characterization and optimization is essential for the rational design of imaging agents.
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| 21. |
- O' Donovan, Daniel H., et al.
(författare)
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The Next Generation of Pattern Recognition Receptor Agonists : Improving Response Rates in Cancer Immunotherapy
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:34, s. 5654-5674
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Tidskriftsartikel (refereegranskat)abstract
- The recent success of checkpoint blocking antibodies has sparked a revolution in cancer immunotherapy. Checkpoint inhibition activates the adaptive immune system leading to durable responses across a range of tumor types, although this response is limited to patient populations with pre-existing tumor infiltrating T cells. Strategies to stimulate the immune system to prime an antitumor response are of intense interest and several groups are now working to develop agents to activate the pattern recognition receptors (PRRs), proteins which detect pathogenic and damage-associated molecules and respond by activating the innate immune response. Although early efforts focused on the Toll-like receptor (TLR) family of membrane-bound PRRs, TLR activation has been associated with both pro- and antitumor effects. Nonetheless, TLR agonists have been deployed as potential anticancer agents in a range of clinical trials. More recently, the cytosolic PRR Stimulator of IFN genes (STING) has attracted attention as another promising target for anticancer drug development, with early clinical data beginning to emerge. Besides STING, several other cytosolic PRR targets have likewise captured the interest of the drug discovery community, including the RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs). In this review, we describe the outlook for activators of PRRs as anticancer therapeutic agents and contrast the earlier generation of TLR agonists with the emerging focus on cytosolic PRR activators, both as single agents and in combination with other cancer immunotherapies.
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| 22. |
- Oorni, Katariina, et al.
(författare)
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Triglyceride-Rich Lipoproteins as a Source of Proinflammatory Lipids in the Arterial Wall
- 2019
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 26:9, s. 1701-1710
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein B -containing lipoproteins include triglyceride-rich lipoproteins (chylomicrons and their remnants, and very low-density lipoproteins and their remnants) and cholesterol-rich low-density lipoprotein particles. Of these, lipoproteins having sizes below 70-80 nm may enter the arterial wall, where they accumulate and induce the formation of atherosclerotic lesions. The processes that lead to accumulation of lipoprotein-derived lipids in the arterial wall have been largely studied with a focus on the low-density lipoprotein particles. However, recent observational and genetic studies have discovered that the triglyceriderich lipoproteins and their remnants are linked with cardiovascular disease risk. In this review, we describe the potential mechanisms by which the triglyceride-rich remnant lipoproteins can contribute to the development of atherosclerotic lesions, and highlight the differences in the atherogenicity between low-density lipoproteins and the remnant lipoproteins.[on SciFinder (R)]
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| 23. |
- Potpara, Tatjana S., et al.
(författare)
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Cardiac Arrhythmias in Patients with Chronic Kidney Disease : Implications of Renal Failure for Antiarrhythmic Drug Therapy
- 2016
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 23:19, s. 2070-2083
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Forskningsöversikt (refereegranskat)abstract
- The kidney has numerous complex interactions with the heart, including shared risk factors (e.g., hypertension, dyslipidemia, etc.) and mutual amplification of morbidity and mortality. Both cardiovascular diseases and chronic kidney disease (CKD) may cause various alterations in cardiovascular system, metabolic homeostasis and autonomic nervous system that may facilitate the occurrence of cardiac arrhythmias. Also, pre-existent or incident cardiac arrhythmias such as atrial fibrillation (AF) may accelerate the progression of CKD. Patients with CKD may experience various cardiac rhythm disturbances including sudden cardiac death. Contemporary management of cardiac arrhythmias includes the use of antiarrhythmic drugs (AADs), catheter ablation and cardiac implantable electronic devices (CIEDs). Importantly, AADs are not used only as the principal treatment strategy, but also as an adjunct therapy in combination with CIEDs, to facilitate their effects or to minimize inappropriate device activation in selected patients. Along with their principal antiarrhythmic effect, AADs may also induce cardiac arrhythmias and the risk for such proarrhythmic effect(s) is particularly increased in patients with reduced left ventricular systolic function or in the setting of electrolyte imbalance. Moreover, CKD itself can induce profound alterations in the pharmacokinetics and pharmacodynamics of many drugs including AADs, thus facilitating the drug accumulation and increased exposure. Hence, the use of AADs in patients with CKD may be challenging. In this review article, we provide an overview of the characteristics of arrhythmogenesis in patients with CKD with special emphasis on the complexity of pharmacokinetics and risk for proarrhythmias when using AADs in patients with cardiac arrhythmias and CKD.
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| 24. |
- Rashedi, Iran, et al.
(författare)
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Autoimmunity and apoptosis - Therapeutic implications
- 2007
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 14:29, s. 3139-3151
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Tidskriftsartikel (refereegranskat)abstract
- Acquisition of a complex immune system during evolution provided organisms with the most effective defense mechanism against "foreign" or "non-self" invaders. This efficient protection against pathogens, however, has been achieved at the expense of a higher risk for "self"-directed reaction or autoimmunity. Establishment of self-tolerance and homeostasis in the immune system is regulated at different physiological stages of immune cells development. The breakdown in discrimination between "self" and "non-self" causes an aberrant immune response against autoantigens that promote damage to the "self" cells and tissue(s), resulting in various autoimmune phenotypes. Whereas activation and clonal proliferation of autoreactive T- and B-lymphocytes underlies the pathogenesis of autoimmune diseases, the mechanism by which self-tolerance is lost and autoimmune responses are induced is not clear yet. Autoimmunity is a multi-step process that occurs as a consequence of complex interaction between genetic susceptibility and non-genetic factors. Programmed cell death, as a key mechanism to regulate immune system function, has a crucial influence on both the selection process of immune cells and the maintenance of this immune tolerance in peripheral repertoire. Thus, defects in apoptotic death pathways may contribute to the development of autoimmune response in susceptible individuals in certain conditions.
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| 25. |
- Rolla, Giovanni, et al.
(författare)
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An Emerging Role for Exhaled Nitric Oxide in Guiding Biological Treatment in Severe Asthma
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:42, s. 7159-7167
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Forskningsöversikt (refereegranskat)abstract
- Asthma is a heterogeneous disease with regard to the inflammatory pathways activated. In recent years, biologic drugs (monoclonal antibodies) directed towards specific components of type 2 inflammation have been approved for the treatment of severe asthma. Phenotyping of patients with severe asthma and evaluation of biomarkers have been recommended to help identify patients who are candidates for treatment with biologics and to monitor treatment responses.Fractional exhaled Nitric Oxide (FeNO) is a biomarker of type 2 inflammation in asthma, signaling activation of Interleukin (IL)-4/IL-13 pathway. FeNO could be useful to assess treatment response or identify candidates for a specific drug that acts on type 2 inflammation mechanisms linked to Nitric Oxide (NO) production, such as the IL-4/IL-13 pathway or upstream processes.The value of FeNO as a biomarker predictive of responses to the biologics available for treating severe asthma is discussed based on the published studies at the moment of the review.
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| 26. |
- Simeon, Saw, et al.
(författare)
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Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors
- 2021
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers. - 0929-8673 .- 1875-533X. ; 28:38, s. 7830-7839
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite continued efforts to develop new treatments, there is an urgent need to discover new drug leads to treat tumors exhibiting primary or secondary resistance to existing drugs. Cell cultures derived from patient-derived orthotopic xenografts are promising pre-clinical models to better predict drug response in cancer recurrence.OBJECTIVE: The aim of the study was to investigate the relationship between the physiochemical properties of drugs and their in vitro potency as well as identifying chemical scaffolds biasedtowards selectivity or promiscuity of such drugs.METHODS: The bioactivities of 158 drugs screened against cell cultures derived from 30 cancer orthotopic patient-derived xenograft (O-PDX) models were considered. Drugs were represented by physicochemical descriptors and chemical structure fingerprints. Supervised learning was employed to model the relationship between features and in vitro potency.RESULTS: Drugs with in vitro potency for alveolar rhabdomyosarcoma and osteosarcoma tend to have a higher number of rings, two carbon-hetero bonds and halogens. Selective and promiscuous scaffolds for these phenotypic targets were identified. Highly-predictive models of in vitro potency were obtained across these 30 targets, which can be applied to unseen molecules via a webserver (https://rnewbie.shinyapps.io/Shobek-master).CONCLUSION: It is possible to identify privileged chemical scaffolds and predict the in vitro potency of unseen molecules across these 30 targets This information and models should be helpful to select which molecules to screen against these primary cultures of pediatric solid tumors.
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| 27. |
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| 28. |
- Tolmachev, Vladimir, et al.
(författare)
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Approaches to improve cellular retention of radiohalogen labels delivered by internalising tumour-targeting proteins and peptides
- 2003
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Ingår i: Current Medicinal Chemistry. - 0929-8673 .- 1875-533X. ; 10:22, s. 2447-60
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Tidskriftsartikel (refereegranskat)abstract
- Specific targeting of radionuclides is a promising approach to improve diagnosis and treatment of tumors. Targeting vectors may be monoclonal antibodies directed toward tumour-specific antigens or regulatory peptides binding to receptors overexpressed on or by malignant cells. Depending on the aim of the procedure and the biokinetics of the targeting vectors, radionuclides with different nuclear properties (decay scheme, half-life, etc.) must be applied. Halogen radioisotopes are attractive since they exhibit a variety of nuclear properties suitable for various applications. At the same time, their chemistry shows great similarities, which enables the use of similar labelling procedures for different nuclides. A problem in using radiohalogens for labelling of tumour-targeting proteins and peptides is that the commonly used radiohalogenation methods provide labels, which, after internalisation and lysosomal digestion, rapidly "leak" from malignant cells as radiohalogenated degradation products. The main reason for such leakage is free diffusion of the radiometabolites through lysosomal and cellular membranes. This review describes current approaches in molecular design to improve cellular retention of radiohalogen labels. These approaches include the use of prosthetic groups for the attachment of radiohalogens to targeting vectors of bulky hydrophilic non-charged molecules, molecules positively charged at lysosomal pH and negatively charged molecules. The emphasis in this paper is on labelling chemistry and the results of the biological testing of labelled compounds.
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| 29. |
- Tolmachev, Vladimir, et al.
(författare)
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Influence of labelling methods on biodistribution and imaging properties of radiolabelled peptides for visualisation of molecular therapeutic targets
- 2010
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:24, s. 2636-2655
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Tidskriftsartikel (refereegranskat)abstract
- Progress in genomics and proteomics provides clinical oncology with new anti-cancer drugs, which target selectively aberrantly expressed membrane proteins and associated signalling pathways in malignant cells. Molecular targeting also enables specific delivery of cytotoxic substances to tumours sparing healthy tissues. Improved selectivity of the treatment reduces side effects and widens the therapeutic window. However, only a part of the patients might benefit from such treatment due to inter- and intrapatient heterogeneity of therapeutic target expression. This makes it necessary to identify patients, who may benefit from targeting therapy. Radiolabelled peptides can provide selective and sensitive detection of molecular therapeutic targets in both primary tumours and metastases in a single non-invasive procedure, making personalised treatment possible. The choice of detection method (single photon emission tomography or positron emission tomography), radionuclide for labelling and labeling chemistry can appreciably influence the imaging property of a tracer. The labelling method might affect the binding affinity, the cellular processing and retention of a radionuclide, the biodistribution of a targeting peptide, and excretion pathways of a non-bound tracer and radiocatabolites. This influences the sensitivity and specificity of the imaging. This influence is exemplified by three classes of tumour-targeting peptides: somatostatin analogues, bombesin analogues and Affibody molecules. The review suggests approaches for selection of an optimal labelling chemistry.
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| 30. |
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| 31. |
- Wen, Kangmei, et al.
(författare)
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Recent Research on Flavonoids and their Biomedical Applications
- 2021
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Ingår i: Current Medicinal Chemistry. - Sharjah : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 28:5, s. 1042-1066
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Forskningsöversikt (refereegranskat)abstract
- Flavonoids, commonly found in various plants, are a class of polyphenolic compounds having a basic structural unit of 2-phenylchromone. Flavonoid compounds have attracted much attention due to their wide biological applications. In order to facilitate further research on the biomedical application of flavonoids, we surveyed the literature published on the use of flavonoids in medicine during the past decade, documented the commonly found structures in natural flavonoids, and summarized their pharmacological activities as well as associated mechanisms of action against a variety of health disorders including chronic inflammation, cancer, cardiovascular complications and hypoglycemia. In this mini-review, we provide suggestions for further research on the biomedical applications of flavonoids. © Bentham Science Publishers
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| 32. |
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| 33. |
- Yuan, Ximing, 1959-, et al.
(författare)
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Iron involvement in multiple signaling pathways of atherosclerosis : A revisited hypothesis
- 2008
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 15:21, s. 2157-2172
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis being a leading death cause in many countries is a chronic inflammatory process in which inflammation, immune activation, and oxidative stress are interactively involved. Some epidemiological and many experimental studies suggest that development of atherosclerosis is associated with the amount of iron stored in the body. Transport of electrons between different forms of iron makes it essential for many fundamental cell functions and signalling. Under pathologic conditions iron may serves as a potential catalyst, particularly in the form of redox-active iron or labile iron, for free radical reactions in oxidative stress and cell damage of atherogenesis. Emerging evidence indicates that cellular iron may participate in various cellular signaling pathways, many of which have been implicated in atherogenesis. These include iron homeostatic control signaling, iron-induced oxidative-responsive transcription factors, iron-induced activation of inflammatory cytokines, and iron-dependent signaling in cell growth and apoptosis. This review highlights research progress on atherosclerosis-relevant iron signaling and revisits our hypothesis on iron and atherosclerosis. We propose that iron may contribute to the pathogenesis of atherosclerosis not only via changes in the body iron amount but also by its regulatory roles in redox-sensitive signaling and inflammatory immune responses of atherosclerosis. © 2008 Bentham Science Publishers Ltd.
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| 34. |
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| 35. |
- Andreasen, Niels, et al.
(författare)
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Amyloid-related biomarkers for Alzheimer's disease.
- 2008
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Ingår i: Current medicinal chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 15:8, s. 766-71
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease (AD) is an age-related disorder that causes brain damage resulting in progressive cognitive impairment and death. Three decades of progress have given us a detailed understanding of the underlying molecular mechanisms. Over the past 10 years, this knowledge has translated into a range of targets for therapy, the most promising of which is amyloid beta (Abeta). An imbalance between the production and clearance of Abeta is thought by many to represent the earliest event in the pathogenesis of AD. Abeta is known to be subject to oligomerisation, a process that increases its synaptotoxicity. The oligomers may aggregate further to proto-fibrils and fibrils, eventually forming senile plaques, the neuropathological hallmark of AD. In this article we review the key aspects of Abeta as a biomarker for AD, including its pathogenicity, the diagnostic performance of different Abeta assays in different settings, and the potential usefulness of Abeta as a surrogate marker for treatment efficacy in clinical trials of novel Abeta-targeting drugs.
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| 36. |
- Carlsson, Maria L., 1959, et al.
(författare)
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Schizophrenia: from dopamine to glutamate and back.
- 2004
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Ingår i: Current medicinal chemistry. - 0929-8673. ; 11:3, s. 267-77
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Tidskriftsartikel (refereegranskat)abstract
- The first part of the present review describes the exciting journey of dopamine stabilizers, starting in the early eighties with the development of the partial dopamine agonist (-)-3-PPP of phenylpiperidine structure, via various compounds with aminotetraline structure with preferential autoreceptor antagonist properties, and then back again to phenylpiperidine compounds carrying substituents on the aromatic ring that transformed them from partial dopamine agonists to partial dopamine receptor antagonists, such as OSU6162. OSU6162 was brought to the clinic and has in preliminary trials showed antidyskinetic and antipsychotic efficacy. The second part of this review describes results from a hypoglutamatergia mouse model for cognitive symptoms of schizophrenia, where we have tested traditional neuroleptics, new generation antipsychotics with marked 5-HT2 vs dopamine D2 receptor blockade as well as a dopamine stabilizer belonging to the partial dopamine receptor antagonist category.
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| 37. |
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| 38. |
- Ekström, Per, et al.
(författare)
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Novel In Situ Activity Assays for the Quantitative Molecular Analysis of Neurodegenerative Processes in the Retina
- 2014
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 21:30, s. 3478-3493
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of neuronal cell death are still only poorly understood, which has hindered the advancement of therapies for many currently untreatable neurodegenerative diseases. This calls for the development of new methods which reveal critical molecular mechanisms of the celldeath machinery with both high sensitivity and cellular resolution. Using animal models for hereditary neurodegeneration in the retina, we have developed or adapted different biochemical assays to determine the enzymatic activities of calpain, poly-ADP-ribose-polymerase (PARP), and histone deacetylase (HDAC) directly and in situ. Additionally, the enzymatic activity of cGMP-dependent protein kinase (PKG) was assessed indirectly using in situ immunohistological techniques to detect PKG-activity-dependent products. Combining these assays with in situ cell death markers revealed close temporospatial correlations, suggesting causal connections between the PKG, HDAC, PARP and calpain activities and neuronal cell death. Using different pharmacological and genetic manipulations, causality could indeed be demonstrated. Surprisingly, the often dramatic rises in metabolic activities didnot match by corresponding increases in expression, highlighting the importance of analyses of protein activities at the cellular level. The above mentioned studies identified a number of metabolic processes previously unknownto be involved in inherited retinal degeneration. Comparing different animal retinal degeneration models uncovered striking similarities in enzymatic activities, suggesting a generality of the destructive pathways. Taken together, these findings provided a number of novel targets for neuroprotection and as such opened up new perspectives for the therapy of hereditary neurodegeneration in the retina and possibly other parts of the central nervous system.
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| 39. |
- Faa, G., et al.
(författare)
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A Developmental Approach to Drug-induced Liver Injury in Newborns and Children
- 2012
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Ingår i: Current Medicinal Chemistry. - 0929-8673. ; 19:27, s. 4581-4594
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Forskningsöversikt (refereegranskat)abstract
- The liver represents the major site of drug metabolism in humans. The developmental changes that occur in the liver's metabolic activity during fetal life and in the perinatal period are at the basis of the varied sensitivity of human newborns to many drugs. The decreased capacity of the fetal and newborn liver to metabolize, detoxify, and excrete drugs - total cytochrome P450 content in the fetal liver being 30% to 60% of adult values - may explain the prolonged actions of many drugs in the newborn, as well as less their potential toxicity. On the other hand, the low levels of phase I (activation) enzymes, producing more polar reactive and often toxic metabolites, could explain the lower incidence of adverse effects of some drugs reported in newborns. Moreover, the greater capacity of newborns to synthesize glutathione is at the basis of their ability in inactivating many toxic metabolites. Here we review the acute and chronic liver toxicity due to the most widely used drugs in the neonate. We will discuss in detail the biochemical profile of the fetal and neonatal liver, and the toxic metabolites formed during the metabolism of the most widely used drugs in the neonate. The histological picture of liver disease related to the therapeutic use of drugs will be discussed, with particular emphasis on the mode of cell death involved in hepatitis induced by different drugs most frequently utilized in the neonatal intensive care units.
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| 40. |
- Gaga, M, et al.
(författare)
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Evaluation and management of severe asthma
- 2007
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Ingår i: Current medicinal chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 14:9, s. 1049-1059
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Tidskriftsartikel (refereegranskat)
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| 41. |
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| 42. |
- Larsson, Rikard, et al.
(författare)
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Clinical Trial Update and Novel Therapeutic Approaches for Metastatic Prostate Cancer.
- 2011
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Ingår i: Current Medicinal Chemistry. - 0929-8673. ; 18, s. 4440-4453
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Tidskriftsartikel (refereegranskat)abstract
- Recurrent prostate cancer (PCa) remains a major clinical challenge. Invasive and metastatic PCa lesions often exhibit a partial and time-limited response to therapy before the cancer progresses and the patient succumbs to the disease. Despite recent advances in early diagnosis and treatment, approximately one-third of treated patients will relapse and become resistant to currently available treatments. In this review we evaluate current treatment practices and recent advances in therapy for localized prostate malignancy and advanced, metastatic prostate cancer. Some of the promising new drugs for PCa treatment include MDV3100, an androgen receptor (AR) antagonist that prevents androgens from binding to the AR and nuclear translocation and co-activator recruitment of the ligand-receptor complex; abiraterone, an orally administered drug that irreversibly inhibits a rate-limiting enzyme in androgen biosynthesis, CYP17; and several newer cytotoxic drugs (epothilones, satraplatin). Key new insights are that cancer stem cells play a role in PCa and that PCa cells are dependent on the AR for proliferation, even in the hormone refractory state of the disease. We also discuss potential molecular targets for new drug candidates for the treatment of metastatic PCa.
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| 43. |
- Lindqvist, Pelle, et al.
(författare)
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Carriership of factor v leiden and evolutionary selection advantage.
- 2008
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Ingår i: Current Medicinal Chemistry. - 0929-8673. ; 15:15, s. 1541-1544
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Tidskriftsartikel (refereegranskat)abstract
- Historically, lethal exsanguinations and severe infections have been two major causes of maternal death. Gene mutations that lower the risk of profuse hemorrhage or severe infections would give a survival advantage. A single mutation of coagulation factor V, known as FV Leiden (FVL), can be such a beneficial mutation. FVL is common among Caucasians and today confers an increased risk of thromboembolism. However, the high prevalence of FVL (up to 15%) in the general population suggests that it has given an evolutionary advantage. In this review, we discuss possible mechanisms of the evolutionary survival advantage associated with FVL. In women, FVL confers lower risk of blood loss and profuse hemorrhage in association with delivery and improves the hemoglobin status. In addition, FVL carriers possibly have a survival advantage during sepsis. In conclusion, the high prevalence of FVL may be the result of one or more evolutionary selection advantages.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Shaat, Nael, et al.
(författare)
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Genetics of gestational diabetes mellitus.
- 2007
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 14:5, s. 569-583
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Forskningsöversikt (refereegranskat)abstract
- About 2-5% of all pregnant women develop gestational diabetes mellitus (GDM) during their pregnancies and the prevalence has increased considerably during the last decade. GDM is a heterogeneous disorder that is defined as carbohydrate intolerance with onset or first recognition during pregnancy. It is manifested when pancreatic beta cells are no longer able to compensate for the increased insulin resistance during pregnancy, but the pathogenesis of the disease is still largely unknown. GDM is considered to result from interaction between genetic and environmental risk factors. Genetic predisposition to GDM has been suggested since GDM clusters in families. Also, women with mutations in MODY (Maturity onset diabetes of the young) genes often present with GDM. In addition, common variants in several candidate genes (e.g. potassium inwardly rectifying channel subfamily J, member 11 [KCNJ11], Glucokinase [GCK], Hepatocyte nuclear factor-1alpha [HNFIA] etc.) have been demonstrated to increase the risk of GDM. Old age, obesity and high fat diet represent some important non-genetic factors. There are several approaches to search for genes predisposing to a polygenic disease like GDM including linkage and association studies, expression profiling and animal models. A combination of several methods is usually necessary. Identification of the underlying genetic causes of GDM will eventually give a better view of the mechanisms that contribute to the pathophysiology of the disease, Furthermore, it may improve options to possibly prevent GDM and complications for the mother and her child. This review focuses on the genetics of GDM and possible implications in clinical practice.
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| 50. |
- Soukup, Ondrej, et al.
(författare)
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Interaction of Nerve Agent Antidotes with Cholinergic Systems
- 2010
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Ingår i: CURRENT MEDICINAL CHEMISTRY. - 0929-8673. ; 17:16, s. 1708-1718
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Forskningsöversikt (refereegranskat)abstract
- The poisoning with organophosphorus compounds represents a life threatening danger especially in the time of terroristic menace. No universal antidote has been developed yet and other therapeutic approaches not related to reactivation of acetylcholinesterase are being investigated. This review describes the main features of the cholinergic system, cholinergic receptors, cholinesterases and their inhibitors. It also focuses on the organophosphorus nerve agents, their properties, effects and a large part describes various possibilities in treatments, mainly traditional oxime therapies based on reactivation of AChE. Furthermore, non-cholinesterase coupled antidotal effects of the oximes are thoroughly discussed. These antidotal effects principally include oxime interactions with muscarinic and nicotinic receptors.
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