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https://www.readbyqxmd.com/read/28315463/in-vitro-biphasic-dissolution-tests-and-their-suitability-for-establishing-in-vitro-in-vivo-correlations-a-historical-review
#1
REVIEW
Aude Pestieau, Brigitte Evrard
For many decades, one of the most critical issues in the pharmaceutical industry has been the poor solubility of some drugs. Indeed, a prerequisite for drug absorption is the presence of dissolved drug at the absorption site and this can be challenging for compounds with low aqueous solubility such as BCS class II (low solubility, high permeability) and IV (low solubility, low permeability) compounds. If the development of oral delivery formulations of these compounds is frequently challenging to formulation scientists in the pharmaceutical industry, the in vitro evaluation of these new formulations is also a great challenge...
March 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28315264/the-evolution-of-the-sigma-2-%C3%AF-2-receptor-from-obscure-binding-site-to-bona-fide-therapeutic-target
#2
Chenbo Zeng, Robert H Mach
The sigma-2 (σ2) receptor represents one of the most poorly understood proteins in cell biology. Although this receptor was identified through in vitro binding studies over 25 years ago, the molecular identity of this protein is currently not unambiguously known, and the results from recent attempts to identify the σ2 receptor through protein purification and mass spectral analysis have been the subject of debate in the literature. However, there is overwhelming data demonstrating that the σ2 receptor is an important biomarker of tumor cell proliferation ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28302108/confirmation-of-plasmodium-falciparum-in-vitro-resistance-to-monodesethylamodiaquine-and-chloroquine-in-dakar-senegal-in-2015
#3
Silman Diawara, Marylin Madamet, Mame Bou Kounta, Gora Lo, Khalifa Ababacar Wade, Aminata Nakoulima, Raymond Bercion, Rémy Amalvict, Mamadou Wague Gueye, Bécaye Fall, Bakary Diatta, Bruno Pradines
BACKGROUND: In response to increasing resistance to anti-malarial drugs, Senegal adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria in 2006. However, resistance of Plasmodium falciparum parasites to artemisinin derivatives, characterized by delayed parasite clearance after treatment with ACT or artesunate monotherapy, has recently emerged and rapidly spread in Southeast Asia. After 10 years of stability with rates ranging from 5.6 to 11...
March 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28300769/aptamers-biomedical-interest-and-applications
#4
EDITORIAL
Cristina Romero-López, Alfredo Berzal-Herranz
Aptamers are short DNA or RNA oligonucleotides specialized in the specific and efficient binding to a target molecule. They are obtained by in vitro selection or evolution processes. It was in 1990 that two independent research groups described the bases of a new in vitro technology for the identification of RNA molecules able to specifically bind to a target [1,2]. Tuerk and Gold established the principals of the in vitro selection process that was named SELEX (Systematic Evolution of Ligands by Exponential enrichment), which is based on iterative cycles of binding, partitioning, and amplification of oligonucleotides from a pool of variant sequences [2]...
March 16, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28300168/zebrafish-caudal-haematopoietic-embryonic-stromal-tissue-chest-cells-support-haematopoiesis
#5
Anja Wolf, Julian Aggio, Clyde Campbell, Francis Wright, Gabriel Marquez, David Traver, David L Stachura
Haematopoiesis is an essential process in early vertebrate development that occurs in different distinct spatial locations in the embryo that shift over time. These different sites have distinct functions: in some anatomical locations specific hematopoietic stem and progenitor cells (HSPCs) are generated de novo. In others, HSPCs expand. HSPCs differentiate and renew in other locations, ensuring homeostatic maintenance. These niches primarily control haematopoiesis through a combination of cell-to-cell signalling and cytokine secretion that elicit unique biological effects in progenitors...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297566/instructive-role-of-the-microenvironment-in-preventing-renal-fibrosis
#6
Kei Matsumoto, Sandhya Xavier, Jun Chen, Yujiro Kida, Mark Lipphardt, Reina Ikeda, Annie Gevertz, Mario Caviris, Antonis K Hatzopoulos, Ivo Kalajzic, James Dutton, Brian B Ratliff, Hong Zhao, Zbygniew Darzynkiewicz, Stefan Rose-John, Michael S Goligorsky
Accumulation of myofibroblasts is a hallmark of renal fibrosis. A significant proportion of myofibroblasts has been reported to originate via endothelial-mesenchymal transition. We initially hypothesized that exposing myofibroblasts to the extract of endothelial progenitor cells (EPCs) could reverse this transition. Indeed, in vitro treatment of transforming growth factor-β1 (TGF-β1)-activated fibroblasts with EPC extract prevented expression of α-smooth muscle actin (α-SMA); however, it did not enhance expression of endothelial markers...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28288827/crispr-cas9-editing-of-the-genome-for-cancer-modeling
#7
REVIEW
Alexis Guernet, Luca Grumolato
The CRISPR/Cas9 revolution has democratized access to genome editing in many biological fields, including cancer research. Cancer results from the multistep accumulation of mutations that confer to the transformed cells certain biological hallmarks typical of the malignant phenotype. One of the major goals in cancer research is to characterize such mutations and assess their implication in the oncogenic process. Through CRISPR/Cas9 technology, genetic aberrations identified in a patient's tumor can now be easily recreated in experimental models, which can then be used for basic research or for more translational applications...
March 10, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28287575/kinetics-of-lagging-strand-dna-synthesis-in-vitro-by-the-bacteriophage-t7-replication-proteins
#8
Alfredo J Hernandez, Charles C Richardson
Here we provide protocols for the kinetic examination of lagging-strand DNA synthesis in vitro by the replication proteins of bacteriophage T7. The T7 replisome is one of the simplest replication systems known, composed of only four proteins, which is an attractive feature for biochemical experiments. Special emphasis is placed on the synthesis of ribonucleotide primers by the T7 primase-helicase, which are used by DNA polymerase to initiate DNA synthesis. Because the mechanisms of DNA replication are conserved across evolution, these protocols should be applicable, or useful as a conceptual springboard, to investigators using other model systems...
February 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28287179/novel-computational-method-for-predicting-polytherapy-switching-strategies-to-overcome-tumor-heterogeneity-and-evolution
#9
Vanessa D Jonsson, Collin M Blakely, Luping Lin, Saurabh Asthana, Nikolai Matni, Victor Olivas, Evangelos Pazarentzos, Matthew A Gubens, Boris C Bastian, Barry S Taylor, John C Doyle, Trever G Bivona
The success of targeted cancer therapy is limited by drug resistance that can result from tumor genetic heterogeneity. The current approach to address resistance typically involves initiating a new treatment after clinical/radiographic disease progression, ultimately resulting in futility in most patients. Towards a potential alternative solution, we developed a novel computational framework that uses human cancer profiling data to systematically identify dynamic, pre-emptive, and sometimes non-intuitive treatment strategies that can better control tumors in real-time...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28283770/multifactorial-level-of-extremostability-of-proteins-can-they-be-exploited-for-protein-engineering
#10
Debamitra Chakravorty, Mohd Faheem Khan, Sanjukta Patra
Research on extremostable proteins has seen immense growth in the past decade owing to their industrial importance. Basic research of attributes related to extreme-stability requires further exploration. Modern mechanistic approaches to engineer such proteins in vitro will have more impact in industrial biotechnology economy. Developing a priori knowledge about the mechanism behind extreme-stability will nurture better understanding of pathways leading to protein molecular evolution and folding. This review is a vivid compilation about all classes of extremostable proteins and the attributes that lead to myriad of adaptations divulged after an extensive study of 6495 articles belonging to extremostable proteins...
March 10, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/28283233/effect-of-transcatheter-aortic-valve-size-and-position-on-valve-in-valve-hemodynamics-an-in%C3%A2-vitro-study
#11
Ali N Azadani, Michael Reardon, Matheus Simonato, Gabriel Aldea, Georg Nickenig, Ran Kornowski, Danny Dvir
OBJECTIVE: Transcatheter heart valve implantation in failed aortic bioprostheses (valve-in-valve [ViV]) is an increasingly used therapeutic option for high-risk patients. However, high postprocedural gradients are a significant limitation of aortic ViV. Our objective was to evaluate Medtronic CoreValve Evolut R ViV hemodynamics in relation to the degree of device oversizing and depth of implantation. METHODS: Evolut R devices of 23 and 26 mm were implanted within 21-, 23-, and 25-mm Hancock II bioprostheses...
February 10, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28279790/peritoneal-bacterial-infection-repressed-the-expression-of-il17d-in-siberia-sturgeon-a-chondrostean-fish-in-the-early-immune-response
#12
Hua Zhu, Ruxing Song, Xiaowen Wang, Hongxia Hu, Zuobing Zhang
IL17s are pro-inflammatory cytokines that play important roles in host fighting against extracellular bacteria and auto-immune and allergic diseases. IL17D is believed to be the most ancient IL17 member and its functions are far from clarity. Although it has been found in invertebrates, jawless fish, teleosts, and tetrapods, it has not been described in chondrostean fish. Moreover, there are discrepancies concerning its expression pattern in these animals. In this study, we cloned and characterized the cDNA of il17d in Siberia sturgeon (Acipenser baerii), a chondrostean fish and commercially important species in aquaculture...
March 6, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28276281/in-vitro-susceptibility-and-resistance-phenotypes-in-contemporary-citrobacter-isolates-in-a-university-hospital-in-crete-greece
#13
Sofia Maraki, Konstantinos Z Vardakas, Viktoria-Eirini Mavromanolaki, Margarita Kyriakidou, George Spais, Diamantis P Kofteridis, George Samonis, Matthew E Falagas
BACKGROUND: Data on Citrobacter spp. susceptibility are scarce. We sought to study the evolution in the susceptibility of 385 Citrobacter spp. at the University Hospital of Heraklion, Crete, Greece during a six-year period (2010-2015). METHODS: Non-duplicate strains isolated from inpatients (intensive care unit, oncology, surgery, internal medicine, paediatrics) and outpatients were studied using Vitek 2. Phenotypic confirmatory tests were applied for detection of β-lactamases and aminoglycoside modifying enzymes...
March 9, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28275062/aptamers-as-valuable-molecular-tools-in-neurosciences
#14
Olga Wolter, Günter Mayer
Aptamers are short nucleic acids that interact with a variety of targets with high affinity and specificity. They have been shown to inhibit biological functions of cognate target proteins, and they are identifiable by an in vitro selection process, also termed SELEX (Systematic Evolution of Ligands by EXponential enrichment). Being nucleic acids, aptamers can be synthesized chemically or enzymatically. The latter renders RNA aptamers compatible with the cell's own transcription machinery and, thus, expressable inside cells...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28269654/a-hybrid-discrete-continuous-model-of-in-vitro-spheroid-tumor-growth-and-drug-response
#15
Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28264568/selection-and-characterization-of-dna-aptamers-for-electrochemical-biosensing-of-carbendazim
#16
Shimaa Eissa, Mohammed Zourob
This article reports a novel aptamer-based impedimetric detection of carbendazim, a commonly used benzimidazole fungicide in agriculture. High affinity and specificity DNA aptamers against carbendazim were successfully selected using systematic evolution of ligand by exponential enrichment (SELEX). The dissociation constants (Kds) of the selected DNA aptamers after 10 in vitro selection cycles were characterized using fluorescence-based assays showing values in the nanomolar range. The aptamer which showed the highest degree of affinity and conformation change was used to fabricate an electrochemical aptasensor via self-assembly of thiol-modified aptamer on gold electrodes...
March 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28264054/delineating-cd4-dependency-of-hiv-1-adaptation-to-infect-low-level-cd4-expressing-target-cells-widens-cellular-tropism-but-severely-impacts-on-envelope-functionality
#17
David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J Duenas-Decamp, Paul R Clapham, Karin J Metzner, Huldrych F Günthard, Alexandra Trkola
A hallmark of HIV-1 infection is the continuously declining number of the virus' predominant target cells, activated CD4+ T cells. With diminishing CD4+ T cell levels, the capacity to utilize alternate cell types and receptors, including cells that express low CD4 receptor levels such as macrophages, thus becomes crucial. To explore evolutionary paths that allow HIV-1 to acquire a wider host cell range by infecting cells with lower CD4 levels, we dissected the evolution of the envelope-CD4 interaction under in vitro culture conditions that mimicked the decline of CD4high target cells, using a prototypic subtype B, R5-tropic strain...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28263610/correlating-membrane-morphological-responses-with-micellar-aggregation-behavior-of-capric-acid-and-monocaprin
#18
Bo Kyeong Yoon, Joshua A Jackman, Min Chul Kim, Tun Naw Sut, Nam-Joon Cho
The interaction of single-chain lipid amphiphiles with phospholipid membranes is relevant to many scientific fields, including molecular evolution, medicine, and biofuels. Two widely studied compounds within this class are the medium-chain saturated fatty acid, capric acid, and its monoglyceride derivative, monocaprin. To date, most studies about these compounds have involved in vitro evaluation of their biological activities, while mechanistic details of how capric acid and monocaprin interact with phospholipid bilayers remain elusive...
March 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28263042/1-3-5-trisubstituted-pyrazoles-as-potent-negative-allosteric-modulators-of-the-mglu2-3-receptors
#19
Michiel Van Gool, Sergio Alvar Alonso De Diego, Oscar Delgado, Andrés A Trabanco, Fabrice Jourdan, Gregor J Macdonald, Marijke Somers, Luc Ver Donck
The metabotropic glutamate subtype 2 (mGlu2) receptor is a presynaptic membrane receptor distributed widely in brain that provides feedback inhibitory control of glutamate release. Inhibition of the mGlu2 receptor function with a negative allosteric modulator (NAM) enhances activity dependent glutamate release which may be of therapeutic benefit for treatment of neurological and psychiatric disorders. An attractive pyrazole hit was identified after a high throughput screening (HTS) campaign. The evolution of this hit is described by structure-activity relationship (SAR) study on specific parts of the molecule...
March 6, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28262975/cancer-cytokines-and-the-relevance-of-3d-cultures-for-studying-those-implicated-in-human-cancers
#20
Ravi Maddaly, Aishwarya Subramaniyan, Harini Balasubramanian
Cancers are complex conditions and involving several factors for oncogenesis and progression. Of the various factors influencing the physiology of cancers, cytokines are known to play significant roles as mediators of functions. Intricate cytokine networks have been identified in cancers and interest in cytokines associated with cancers has been gaining ground. Of late, some of these cytokines are even identified as potential targets for cancer therapy apart from a few others such as IL-6 being identified as markers for disease prognosis...
March 6, 2017: Journal of Cellular Biochemistry
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