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Sökning: L773:1424 8247 OR L773:1424 8247 > Forskningsöversikt

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1.
  • Bjerkan, Louise, et al. (författare)
  • Multiple functions of the new cytokine-based antimicrobial peptide thymic stromal lymphopoietin (TSLP)
  • 2016
  • Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 9:3
  • Forskningsöversikt (refereegranskat)abstract
    • Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs), with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34) that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.
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2.
  • Cooper, Callum J., et al. (författare)
  • Enhancing Whole Phage Therapy and Their Derived Antimicrobial Enzymes through Complex Formulation
  • 2018
  • Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 11:2
  • Forskningsöversikt (refereegranskat)abstract
    • The resurgence of research into phage biology and therapy is, in part, due to the increasing need for novel agents to treat multidrug-resistant infections. Despite a long clinical history in Eastern Europe and initial success within the food industry, commercialized phage products have yet to enter other sectors. This relative lack of success is, in part, due to the inherent biological limitations of whole phages. These include (but are not limited to) reaching target sites at sufficiently high concentrations to establish an infection which produces enough progeny phages to reduce the bacterial population in a clinically meaningful manner and the limited host range of some phages. Conversely, parallels can be drawn between antimicrobial enzymes derived from phages and conventional antibiotics. In the current article the biological limitations of whole phage-based therapeutics and their derived antimicrobial enzymes will be discussed. In addition, the ability of more complex formulations to address these issues, in the context of medical and non-medical applications, will also be included.
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3.
  • Fani, Melpomeni, et al. (författare)
  • Current Status of Radiopharmaceuticals for the Theranostics of Neuroendocrine Neoplasms
  • 2017
  • Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 10:1
  • Forskningsöversikt (refereegranskat)abstract
    • Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs). Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics) of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr), other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them. The Glucagon-Like Peptide-1 Receptor (GLP-1R) is highly expressed in benign insulinomas, the Cholecystokinin 2 (CCK2)/Gastrin receptor is expressed in different NENs, in particular medullary thyroid cancer, and the Glucose-dependent Insulinotropic Polypeptide (GIP) receptor was found to be expressed in gastrointestinal and bronchial NENs, where interestingly, it is present in most of the sstr-negative and GLP-1R-negative NENs. Also in the field of sstr targeting new discoveries brought into light an alternative approach with the use of radiolabeled somatostatin receptor antagonists, instead of the clinically used agonists. The purpose of this review is to present the current status and the most innovative strategies for the diagnosis and treatment (theranostics) of neuroendocrine neoplasms using a cadre of radiolabeled regulatory peptides targeting their receptors.
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4.
  • Källén, Bengt, et al. (författare)
  • The Use of Central Nervous System Active Drugs During Pregnancy
  • 2013
  • Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 6:10, s. 1221-1286
  • Forskningsöversikt (refereegranskat)abstract
    • CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011) are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found.
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5.
  • Natarajan Arul, Murugan, et al. (författare)
  • A Review on Parallel Virtual Screening Softwares for High-Performance Computers
  • 2022
  • Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:1, s. 63-
  • Forskningsöversikt (refereegranskat)abstract
    • Drug discovery is the most expensive, time-demanding, and challenging project in biopharmaceutical companies which aims at the identification and optimization of lead compounds from large-sized chemical libraries. The lead compounds should have high-affinity binding and specificity for a target associated with a disease, and, in addition, they should have favorable pharmacodynamic and pharmacokinetic properties (grouped as ADMET properties). Overall, drug discovery is a multivariable optimization and can be carried out in supercomputers using a reliable scoring function which is a measure of binding affinity or inhibition potential of the drug-like compound. The major problem is that the number of compounds in the chemical spaces is huge, making the computational drug discovery very demanding. However, it is cheaper and less time-consuming when compared to experimental high-throughput screening. As the problem is to find the most stable (global) minima for numerous protein-ligand complexes (on the order of 10(6) to 10(12)), the parallel implementation of in silico virtual screening can be exploited to ensure drug discovery in affordable time. In this review, we discuss such implementations of parallelization algorithms in virtual screening programs. The nature of different scoring functions and search algorithms are discussed, together with a performance analysis of several docking softwares ported on high-performance computing architectures.
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6.
  • Velikyan, Irina, 1966- (författare)
  • (Radio)Theranostic Patient Management in Oncology Exemplified by Neuroendocrine Neoplasms, Prostate Cancer, and Breast Cancer
  • 2020
  • Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 13:3
  • Forskningsöversikt (refereegranskat)abstract
    • The role of nuclear medicine in the management of oncological patients has expanded during last two decades. The number of radiopharmaceuticals contributing to the realization of theranostics/radiotheranostics in the context of personalized medicine is increasing. This review is focused on the examples of targeted (radio)pharmaceuticals for the imaging and therapy of neuroendocrine neoplasms (NENs), prostate cancer, and breast cancer. These examples strongly demonstrate the tendency of nuclear medicine development towards personalized medicine.
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7.
  • Zhang, Xiaonan, et al. (författare)
  • Targeting Loss of Heterozygosity : A Novel Paradigm for Cancer Therapy
  • 2021
  • Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 14:1
  • Forskningsöversikt (refereegranskat)abstract
    • Loss of heterozygosity (LOH) is a common genetic event in the development of cancer. In certain tumor types, LOH can affect more than 20% of the genome, entailing loss of allelic variation in thousands of genes. This reduction of heterozygosity creates genetic differences between tumor and normal cells, providing opportunities for development of novel cancer therapies. Here, we review and summarize (1) mutations associated with LOH on chromosomes which have been shown to be promising biomarkers of cancer risk or the prediction of clinical outcomes in certain types of tumors; (2) loci undergoing LOH that can be targeted for development of novel anticancer drugs as well as (3) LOH in tumors provides up-and-coming possibilities to understand the underlying mechanisms of cancer evolution and to discover novel cancer vulnerabilities which are worth a further investigation in the near future.
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8.
  • Coccia, Francesco, et al. (författare)
  • Vitamin D and Osteogenesis Imperfecta in Pediatrics
  • 2023
  • Ingår i: Pharmaceuticals. - 1424-8247. ; 16:5
  • Forskningsöversikt (refereegranskat)abstract
    • Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI.
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9.
  • Eriksson, Olof, et al. (författare)
  • Radiotracers for Imaging of Fibrosis : Advances during the Last Two Decades and Future Directions
  • 2023
  • Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 16:11
  • Forskningsöversikt (refereegranskat)abstract
    • Fibrosis accompanies various pathologies, and there is thus an unmet medical need for non-invasive, sensitive, and quantitative methods for the assessment of fibrotic processes. Currently, needle biopsy with subsequent histological analysis is routinely used for the diagnosis along with morphological imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). However, none of these imaging techniques are sufficiently sensitive and accurate to detect minor changes in fibrosis. More importantly, they do not provide information on fibrotic activity on the molecular level, which is critical for fundamental understanding of the underlying biology and disease course. Molecular imaging technology using positron emission tomography (PET) offers the possibility of imaging not only physiological real-time activity, but also high-sensitivity and accurate quantification. This diagnostic tool is well established in oncology and has exhibited exponential development during the last two decades. However, PET diagnostics has only recently been widely applied in the area of fibrosis. This review presents the progress of development of radiopharmaceuticals for non-invasive detection of fibrotic processes, including the fibrotic scar itself, the deposition of new fibrotic components (fibrogenesis), or the degradation of existing fibrosis (fibrolysis).
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10.
  • Riu, Federico, et al. (författare)
  • Antibiotics and Carbohydrate-Containing Drugs Targeting Bacterial Cell Envelopes : An Overview
  • 2022
  • Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:8
  • Forskningsöversikt (refereegranskat)abstract
    • Certain bacteria constitute a threat to humans due to their ability to escape host defenses as they easily develop drug resistance. Bacteria are classified into gram-positive and gram-negative according to the composition of the cell membrane structure. Gram-negative bacteria have an additional outer membrane (OM) that is not present in their gram-positive counterpart; the latter instead hold a thicker peptidoglycan (PG) layer. This review covers the main structural and functional properties of cell wall polysaccharides (CWPs) and PG. Drugs targeting CWPs are discussed, both noncarbohydrate-related (β-lactams, fosfomycin, and lipopeptides) and carbohydrate-related (glycopeptides and lipoglycopeptides). Bacterial resistance to these drugs continues to evolve, which calls for novel antibacterial approaches to be developed. The use of carbohydrate-based vaccines as a valid strategy to prevent bacterial infections is also addressed.
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