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https://www.readbyqxmd.com/read/29679802/the-evolving-role-of-dna-inter-strand-crosslinks-in-chemotherapy
#1
REVIEW
Halley B Rycenga, David T Long
DNA crosslinking agents make up a broad class of chemotherapy agents that target rapidly dividing cancer cells by disrupting DNA synthesis. These drugs differ widely in both chemical structure and biological effect. In cells, crosslinking agents can form multiple types of DNA lesions with varying efficiencies. Inter-strand crosslinks (ICLs) are considered to be the most cytotoxic lesion, creating a covalent roadblock to replication and transcription. Despite over 50 years in the clinic, the use of crosslinking agents that specialize in the formation of ICLs remains limited, largely due to high toxicity in patients...
April 18, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29679795/self-controlled-release-of-oxaliplatin-prodrug-from-d-%C3%AE-tocopheryl-polyethylene-glycol-1000-succinate-tpgs-functionalized-mesoporous-silica-nanoparticles-for-cancer-therapy
#2
Chaoyu Liang, Heping Wang, Min Zhang, Wei Cheng, Zihuang Li, Junpeng Nie, Gan Liu, Daizheng Lian, Zhenhua Xie, Laiqiang Huang, Xiaowei Zeng
Oxaliplatin is a promising antitumor drug, but its effectiveness is limited by its side effects in vivo. In this study, we introduced an Oxaliplatin prodrug (Oxa(IV)) self-controlled release strategy, in which Oxa(IV) is encapsulated by TPGS functionalized mesoporous silica nanoparticles (MSNs), and its release is controlled by biological stimuli, such as acidic environments in tumor tissue and high concentrations of reductants in cancer cells. Despite the lack of auxiliary "gatekeepers" to MSNs, this simplified model of Oxa(IV)-MSNs-TPGS could fine-tune the movements of the drug release...
April 16, 2018: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29679778/recapitulating-spatiotemporal-tumor-heterogeneity-in-vitro-through-engineered-breast-cancer-microtissues
#3
Claudia Mazio, Costantino Casale, Giorgia Imparato, Francesco Urciuolo, Paolo Antonio Netti
Tumor and microenvironmental heterogeneity hinders the study of breast cancer biology and the assessment of therapeutic strategies, being associated with high variability and drug resistance. In this context, it is mandatory to develop three-dimensional breast tumor models able to reproduce this heterogeneity and the dynamic interaction occurring between tumor cells and microenvironment. Here we show a new breast cancer microtissue model (T-µTP) uniquely able to present intra-tumor morphological heterogeneity in a dynamic and responsive endogenous matrix...
April 18, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29679708/the-impact-of-polymers-on-3d-microstructure-and-controlled-release-of-sildenafil-citrate-from-hydrophilic-matrices
#4
Anna Krupa, Zbisław Tabor, Jacek Tarasiuk, Beata Strach, Krzysztof Pociecha, Elżbieta Wyska, Sebastian Wroński, Ewelina Łyszczarz, Renata Jachowicz
Sildenafil citrate has short biological half-life in humans. Thus, matrix tablets of controlled release were designed and prepared by compaction on the basis of hydrophilic polymers, i.e. HPMC, sodium alginate, carbomer, poloxamer and their mixtures. The impact of these polymers on sildenafil release in vitro and its pharmacokinetics in vivo was evaluated. Since drug release rate from hydrophilic matrices can be govern by the porosity of the matrix, the microstructure of tablets was studied using X-ray microcomputed tomography...
April 18, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29679640/cepfostering-efficacy-and-toxicity-evaluation-of-traditional-chinese-medicine-and-natural-products
#5
REVIEW
Tong Wu, Gui-Yuan Yu, Jia Xiao, Chang Yan, Hiroshi Kurihara, Yi-Fang Li, Kwok-Fai So, Rong-Rong He
Efficacy and safety assessments are essential thresholds for drug candidates from preclinical to clinical research. Conventional mammalian in vivo models cannot offer rapid pharmacological and toxicological screening, whereas cell-based or cell-free in vitro systems often lead to inaccurate results because of the lack of physiological environment. Within the avian species, chick is the first bird to have its genome sequencing. Meantime, chick embryo is an easily operating, relatively transparent and extensively accessible model, whose physiological and pathological alterations can be visualized by egg candler, staining and image technologies...
April 18, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29679485/identification-and-structure-elucidation-of-the-proresolving-mediators-provides-novel-leads-for-resolution-pharmacology
#6
REVIEW
Jesmond Dalli, Charles N Serhan
Inflammatory diseases are a major socioeconomic burden, with the incidence of such conditions on the rise, especially in western societies. For decades, the primary treatment paradigm for many of these conditions was to develop drugs that inhibit or antagonize the production and biological actions of molecules that were thought to be the culprits in propagating disease, these include cytokines and eicosanoids. This approach is effective in controlling disease propagation; however, long-term exposure to these anti-inflammatories is also associated with many side effects, some of which severe, including immune-suppression...
April 21, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29679078/fluorophore-labeling-of-a-cell-penetrating-peptide-significantly-alters-the-mode-and-degree-of-biomembrane-interaction
#7
Sofie Fogh Hedegaard, Mohammed Sobhi Derbas, Tania Kjellerup Lind, Marina Robertnova Kasimova, Malene Vinther Christensen, Maria Høtoft Michaelsen, Richard A Campbell, Lene Jorgensen, Henrik Franzyk, Marité Cárdenas, Hanne Mørck Nielsen
The demand for highly efficient macromolecular drugs, used in the treatment of many severe diseases, is continuously increasing. However, the hydrophilic character and large molecular size of these drugs significantly limit their ability to permeate across cellular membranes and thus impede the drugs in reaching their target sites in the body. Cell-penetrating peptides (CPP) have gained attention as promising drug excipients, since they can facilitate drug permeation across cell membranes constituting a major biological barrier...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29678733/pharmacokinetics-of-lipid-drug-conjugates-loaded-into-liposomes
#8
REVIEW
Rea D Signorell, Paola Luciani, Davide Brambilla, Jean-Christophe Leroux
Drugs that are neither lipophilic nor suitable for encapsulation via remote loading procedures are generally characterized by low entrapment efficiencies and poor retention in liposomes. One approach to circumvent this problem consists in covalently linking a lipid to the drug molecule in order to permit its insertion into the vesicle membrane. The nature of the conjugated lipid and linker, as well as the composition of the liposomal bilayer were found to have a profound impact on the pharmacokinetic properties and biodistribution of the encapsulated drugs as well as on their biological activity...
April 17, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29678658/essentiality-conservation-evolutionary-pressure-and-codon-bias-in-bacterial-genomes
#9
Maddalena Dilucca, Giulio Cimini, Andrea Giansanti
Essential genes constitute the core of genes which cannot be mutated too much nor lost along the evolutionary history of a species. Natural selection is expected to be stricter on essential genes and on conserved (highly shared) genes, than on genes that are either nonessential or peculiar to a single or a few species. In order to further assess this expectation, we study here how essentiality of a gene is connected with its degree of conservation among several unrelated bacterial species, each one characterised by its own codon usage bias...
April 17, 2018: Gene
https://www.readbyqxmd.com/read/29678593/characterisation-of-aptamer-bc-007-substance-and-product-using-circular-dichroism-and-nuclear-magnetic-resonance-spectroscopy
#10
Hardy Weisshoff, Katrin Wenzel, Sarah Schulze-Rothe, Heike Nikolenko, Hanna Davideit, Niels-Peter Becker, Peter Göttel, G Susan Srivatsa, Margitta Dathe, Johannes Müller, Annekathrin Haberland
Possible unwanted folding of biopharmaceuticals during manufacturing and storage has resulted in analysis schemes compared to small molecules that includes bioanalytical characterisation besides chemical characterisation. Whether bioanalytical characterisation is required for nucleotide-based drugs, may be decided on a case-by-case basis. Nucleotide-based pharmaceuticals, if chemically synthesised, occupy an intermediate position between small-molecule drugs and biologics. Here, we tested whether a physicochemical characterisation of a nucleotide-based drug substance, BC 007, was adequate, using circular dichroism (CD) spectroscopy...
April 17, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29678461/design-synthesis-evaluation-and-molecular-docking-of-ursolic-acid-derivatives-containing-a-nitrogen-heterocycle-as-anti-inflammatory-agents
#11
Zhi-Yu Wei, Ke-Qiang Chi, Ke-Si Wang, Jie Wu, Li-Ping Liu, Hu-Ri Piao
Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by 1 H NMR, 13 C NMR, and HRMS. Most of the synthesized compounds showed pronounced anti-inflammatory effects at 100 mg/kg. In particular, compound 11b, which displayed the most potent anti-inflammatory activity of all of the compounds prepared, with 69.76% inhibition after intraperitoneal administration, was more potent than the reference drugs indomethacin and ibuprofen...
April 11, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29678446/cycloartane-type-sapogenol-derivatives-inhibit-nfb-activation-as-chemopreventive-strategy-for-inflammation-induced-prostate-carcinogenesis
#12
Bilge Debeleç-Bütüner, Mert Burak Öztürk, Özgür Tağ, İsmail Hakkı Akgün, Günay Yetik-Anacak, Erdal Bedir, Kemal Sami Korkmaz
Chronic inflammation is associated to 25% of cancer cases according to epidemiological data. Therefore, inhibition of inflammation-induced carcinogenesis can be an efficient therapeutic approach for cancer chemoprevention in drug development studies. It is also determined that anti-inflammatory drugs reduce cancer incidence. Cell culture-based in vitro screening methods are used as a fast and efficient method to investigate the biological activities of the biomolecules. In addition, saponins are molecules that are isolated from natural sources and are known to have potential for tumor inhibition...
April 17, 2018: Steroids
https://www.readbyqxmd.com/read/29678288/internalization-of-g-protein-coupled-receptors-implication-in-receptor-function-physiology-and-diseases
#13
REVIEW
Davide Calebiro, Amod Godbole
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and mediate the effects of numerous hormones and neurotransmitters. The nearly 1000 GPCRs encoded by the human genome regulate virtually all physiological functions and are implicated in the pathogenesis of prevalent human diseases such as thyroid disorders, hypertension or Parkinson's disease. As a result, 30-50% of all currently prescribed drugs are targeting these receptors. Once activated, GPCRs induce signals at the cell surface...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678262/tolfenamic-acid
#14
Sofia Ahmed, Muhammad Ali Sheraz, Iqbal Ahmad
Tolfenamic acid (TA) is a nonsteroidal antiinflammatory drug and belongs to the group of fenamates. It is used as a potent pain reliever in the treatment of acute migraine attacks, and disorders like dysmenorrhea, rheumatoid, and osteoarthritis. TA has shown excellent in vitro antibacterial activity against certain ATCC strains of bacteria when complexed with bismuth(III). It has also been reported to block pathological processes associated with Alzheimer's disease. In the recent past, TA has also been used as a novel anticancer agent for the treatment of various cancers...
2018: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/29678260/ganciclovir
#15
Abdullah A Al-Badr, Tariq D S Ajarim
Ganciclovir is synthetic nucleoside analog of guanine closely related to acyclovir but has greater activity against cytomegalovirus. This comprehensive profile on ganciclovir starts with a description of the drug: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and application of the drug are explained. The methods that were used for the preparation of ganciclovir are described and their respective schemes are outlined. The methods which were used for the physical characterization of the dug are: ionization constant, solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry...
2018: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/29678192/engineering-in-vitro-stem-cell-based-vascularized-bone-models-for-drug-screening-and-predictive-toxicology
#16
REVIEW
Alessandro Pirosa, Riccardo Gottardi, Peter G Alexander, Rocky S Tuan
The production of veritable in-vitro models of bone tissue is essential to understand the biology of bone and its surrounding environment, to analyze the pathogenesis of bone diseases (e.g., osteoporosis, osteoarthritis, osteomyelitis, etc.), to develop effective therapeutic drug screening, and to test potential therapeutic strategies. Dysregulated interactions between vasculature and bone cells are often related to the aforementioned pathologies, underscoring the need for a bone model that contains engineered vasculature...
April 20, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29678120/psoriasis-management-in-actual-clinical-practice-a-6-year-retrospective-study-of-845-patients
#17
Pinar Incel Uysal, Buket Sahin, Basak Yalcin, Afra Alkan, Selcen Yuksel
BACKGROUND: Over the past years, with the availability of relatively well tolerated, very effective but expensive drugs, biologics, treatment of psoriasis has dramatically shifted from inpatient modalities to outpatient ones. Relatively little is known about true life practices regarding psoriasis treatment in our country. AIMS: To assess the impact of introduction of conventional drugs and biological drugs on medical resource use of psoriasis patients. STUDY DESIGN: A retrospective chart review was performed...
April 20, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29677485/octapeptins-lipopeptide-antibiotics-against-multidrug-resistant-superbugs
#18
Antoine Abou Fayad, Jennifer Herrmann, Rolf Müller
Antimicrobial resistance is increasing at an alarming rate. Polymyxin, one of the few antibiotics of last resort, is heavily affected. In this issue of Cell Chemical Biology, Velkov et al. (2018) present a promising alternative: octapeptin lipopeptide antibiotics active against multidrug- and extensively drug-resistant Gram-negative bacteria, which might help overcoming resistance toward polymyxins.
April 19, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29677376/endothelial-protein-c-targeting-liposomes-show-enhanced-uptake-and-improved-therapeutic-efficacy-in-human-retinal-endothelial-cells
#19
Anthoula Arta, Anne Z Eriksen, Fredrik Melander, Paul Kempen, Michael Larsen, Thomas L Andresen, Andrew J Urquhart
Purpose: To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid-loaded functionalized liposomes that exhibit both enhanced uptake by HRECs and superior biologic activity compared to nontargeting liposomes and free drug. Methods: EPCR expression of HRECs was investigated through flow cytometry and Western blot assays...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29677130/lipid-biosynthesis-as-an-antifungal-target
#20
REVIEW
Jiao Pan, Cuiting Hu, Jae-Hyuk Yu
Lipids, commonly including phospholipids, sphingolipids, fatty acids, sterols, and triacylglycerols (TAGs), are important biomolecules for the viability of all cells. Phospholipids, sphingolipids, and sterols are important constituents of biological membranes. Many lipids play important roles in the regulation of cell metabolism by acting as signaling molecules. Neutral lipids, including TAGs and sterol esters (STEs), are important storage lipids in cells. In view of the importance of lipid molecules, this review briefly summarizes the metabolic pathways for sterols, phospholipids, sphingolipids, fatty acids, and neutral lipids in fungi and illustrates the differences between fungal and human (or other mammalian) cells, especially in relation to lipid biosynthetic pathways...
April 20, 2018: Journal of Fungi (Basel, Switzerland)
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