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https://www.readbyqxmd.com/read/29474788/unveiling-the-aggregation-behavior-of-doxorubicin-hydrochloride-in-aqueous-solution-of-1-octyl-3-methylimidazolium-chloride-and-the-effect-of-bile-salt-on-these-aggregates-a-microscopic-study
#1
Arghajit Pyne, Sangita Kundu, Pavel Banerjee, Nilmoni Sarkar
In this article, we have unveiled the aggregation behavior of a potent chemotherapeutic drug, doxorubicin hydrochloride (Dox) in a well known imidazolium based surface active ionic liquid (SAIL), 1-octyl-3-methylimidazolium chloride (C8mimCl). The aggregates formed by Dox in C8mimCl have been characterized using dynamic light scattering (DLS), fluorescence lifetime imaging microscopy (FLIM), high resolution transmission electron microscopy (HR-TEM), analytical transmission electron microscopy (analytical TEM), field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and fourier-transform infrared spectroscopy (FTIR) measurements...
February 23, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29472703/suppression-of-the-erk-srf-axis-facilitates-somatic-cell-reprogramming
#2
Sejong Huh, Hwa-Ryung Song, Geuk-Rae Jeong, Hyejin Jang, Nan-Hee Seo, Ju-Hyun Lee, Ji-Yeun Yi, Byongsun Lee, Hyun Woo Choi, Jeong Tae Do, Jin-Su Kim, Soo-Hong Lee, Jae-Won Jung, Taekyu Lee, Jaekyung Shim, Myung-Kwan Han, Tae-Hee Lee
The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation...
February 23, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29472542/active-colloids-as-mobile-microelectrodes-for-unified-label-free-selective-cargo-transport
#3
Alicia M Boymelgreen, Tov Balli, Touvia Miloh, Gilad Yossifon
Utilization of active colloids to transport both biological and inorganic cargo has been widely examined in the context of applications ranging from targeted drug delivery to sample analysis. In general, carriers are customized to load one specific target via a mechanism distinct from that driving the transport. Here we unify these tasks and extend loading capabilities to include on-demand selection of multiple nano/micro-sized targets without the need for pre-labelling or surface functionalization. An externally applied electric field is singularly used to drive the active cargo carrier and transform it into a mobile floating electrode that can attract (trap) or repel specific targets from its surface by dielectrophoresis, enabling dynamic control of target selection, loading and rate of transport via the electric field parameters...
February 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29470968/multiple-sclerosis-mechanisms-and-immunotherapy
#4
REVIEW
Clare Baecher-Allan, Belinda J Kaskow, Howard L Weiner
Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system...
February 21, 2018: Neuron
https://www.readbyqxmd.com/read/29466002/development-of-potent-inhibitors-of-receptor-tyrosine-kinases-by-ligand-based-drug-design-and-target-biased-phenotypic-screening
#5
Samuel H Myers, Carolin Temps, Douglas R Houston, Valerie G Brunton, Asier Unciti-Broceta
Pyrazolopyrimidines with potent antiproliferative properties were developed by an adaptive strategy that applies ligand-based design and phenotypic screening iteratively and is informed by biochemical assays. To drive development toward specific oncopathways, compounds were tested against cancer cells that overexpress, or not, AXL kinase. Identified phenotypic hits were found to inhibit oncotargets AXL, RET, and FLT3. Subsequent optimization generated antiproliferative lead compounds with unique selectivity profiles, including selective AXL inhibitors and a highly potent inhibitor of FLT3...
February 21, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29463552/integrated-pharmacokinetic-pharmacodynamic-model-of-a-bispecific-cd3xcd123-dart%C3%A2-molecule-in-nonhuman-primates-evaluation-of-activity-and-impact-of-immunogenicity
#6
Olivia Campagne, Audrey Delmas, Sylvain Fouliard, Marylore Chenel, Gurunadh R Chichili, Hua Li, Ralph Alderson, Jean-Michel Scherrmann, Donald E Mager
PURPOSE: Flotetuzumab (MGD006 or S80880) is a bispecific molecule that recognizes CD3 and CD123 membrane proteins, redirecting T-cells to kill CD123-expressing cells for the treatment of acute myeloid leukemia. In this study, we developed a mathematical model to characterize MGD006 exposure-response relationships and to assess the impact of its immunogenicity in cynomolgus monkeys. EXPERIMENTAL DESIGN: 32 animals received multiple escalating doses (100-300-600-1000 ng/kg/day) via intravenous infusion continuously 4-days a week...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29463543/mesoscopic-energy-minimization-drives-pseudomonas-aeruginosa-biofilm-morphologies-and-consequent-stratification-of-antibiotic-activity-based-on-cell-metabolism
#7
M V Sheraton, K H Yam, C H Tan, H S Oh, E Mancini, L Yang, S A Rice, P M A Sloot
Segregation of bacteria based on their metabolic activity in biofilms plays an important role in the development of antibiotic drug resistance. Mushroom-shaped biofilm structures, which are reported for many bacteria, exhibit topographically varying levels of multiple drug resistance from the cap of the mushroom to its stalk. Understanding the dynamics behind the formation of such structures can aid in design of drug delivery systems, antibiotics, or physical systems for removal of biofilms. We explore the development of metabolically heterogenous Pseudomonas aeruginosa biofilms using numerical models and laboratory knock-out experiments on wild-type and chemotaxis deficient mutants...
February 20, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29461260/hemolysis-and-immune-regulation
#8
Hui Zhong, Karina Yazdanbakhsh
PURPOSE OF REVIEW: Hemolytic anemias caused by premature destruction of red blood cells occur in many disorders including hemoglobinopathies, autoimmune conditions, during infection or following reaction to drugs or transfusions. Recent studies which will be reviewed here have uncovered several novel mechanisms by which hemolysis can alter immunological functions and increase the risk of severe complications in hemolytic disorders. RECENT FINDINGS: Plasma-free heme can induce the formation of neutrophil extracellular traps (NETs) through reactive oxygen species signaling...
February 15, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29459867/the-multirole-of-liposomes-in-therapy-and-prevention-of-infectious-diseases
#9
REVIEW
Roberto Nisini, Noemi Poerio, Sabrina Mariotti, Federica De Santis, Maurizio Fraziano
Liposomes are closed bilayer structures spontaneously formed by hydrated phospholipids that are widely used as efficient delivery systems for drugs or antigens, due to their capability to encapsulate bioactive hydrophilic, amphipathic, and lipophilic molecules into inner water phase or within lipid leaflets. The efficacy of liposomes as drug or antigen carriers has been improved in the last years to ameliorate pharmacokinetics and capacity to release their cargo in selected target organs or cells. Moreover, different formulations and variations in liposome composition have been often proposed to include immunostimulatory molecules, ligands for specific receptors, or stimuli responsive compounds...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459865/the-role-of-mst1-in-lymphocyte-homeostasis-and-function
#10
REVIEW
Jiali Cheng, Yukai Jing, Danqing Kang, Lu Yang, Jingwen Li, Ze Yu, Zican Peng, Xingbo Li, Yin Wei, Quan Gong, Richard J Miron, Yufeng Zhang, Chaohong Liu
The Hippo pathway is an evolutionarily conserved pathway crucial for regulating tissue size and for limiting cancer development. However, recent work has also uncovered key roles for the mammalian Hippo kinases, Mst1/2, in driving appropriate immune responses by directing T cell migration, morphology, survival, differentiation, and activation. In this review, we discuss the classical signaling pathways orchestrated by the Hippo signaling pathway, and describe how Mst1/2 direct T cell function by mechanisms not seeming to involve the classical Hippo pathway...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459856/the-immune-and-non-immune-pathways-that-drive-chronic-gastrointestinal-helminth-burdens-in-the-wild
#11
Simon A Babayan, Wei Liu, Graham Hamilton, Elizabeth Kilbride, Evelyn C Rynkiewicz, Melanie Clerc, Amy B Pedersen
Parasitic helminths are extremely resilient in their ability to maintain chronic infection burdens despite (or maybe because of) their hosts' immune response. Explaining how parasites maintain these lifelong infections, identifying the protective immune mechanisms that regulate helminth infection burdens, and designing prophylactics and therapeutics that combat helminth infection, while preserving host health requires a far better understanding of how the immune system functions in natural habitats than we have at present...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29457201/validity-of-oral-fluid-test-for-delta-9-tetrahydrocannabinol-in-drivers-using-the-2013-national-roadside-survey-data
#12
Huiyan Jin, Sharifa Z Williams, Stanford T Chihuri, Guohua Li, Qixuan Chen
BACKGROUND: Driving under the influence of marijuana is a serious traffic safety concern in the United States. Delta 9-tetrahydrocannabinol (THC) is the main active compound in marijuana. Although blood THC testing is a more accurate measure of THC-induced impairment, measuring THC in oral fluid is a less intrusive and less costly method of testing. METHODS: We examined whether the oral fluid THC test can be used as a valid alternative to the blood THC test using a sensitivity and specificity analysis and a logistic regression, and estimate the quantitative relationship between oral fluid THC concentration and blood THC concentration using a correlation analysis and a linear regression on the log-transformed THC concentrations...
February 19, 2018: Injury Epidemiology
https://www.readbyqxmd.com/read/29456273/the-effects-of-acute-cannabis-use-on-nontraffic-injury-risk-reviewing-the-available-literature-and-identifying-ways-forward
#13
Gabriel Andreuccetti, Yu Ye, Jaewook Kang, Rachael Korcha, Jane A Witbrodt, Heraclito B Carvalho, Cheryl J Cherpitel
Recent evidence has indicated that cannabis use before driving is associated with a modest but increased risk for traffic-related injuries. However, the question of whether recent cannabis use is associated with a greater risk for other types of injuries remains unanswered. Aiming to understand better how acute cannabis use might affect the risk for all causes of injury, we have summarized the limited data available in the literature on the risk of non-traffic injuries associated with recent cannabis use. Very few studies were able to provide estimate risks for all injuries or injuries other than those related to road traffic injuries, with the limited evidence available showing mixed findings...
June 2017: Contemporary Drug Problems
https://www.readbyqxmd.com/read/29453841/beyond-cost-benefit-analysis-in-the-governance-of-synthetic-biology
#14
Wendell Wallach, Marc Saner, Gary Marchant
For many innovations, oversight fits nicely within existing governance mechanisms; nevertheless, others pose unique public health, environmental, and ethical challenges. Synthetic artemisinin, for example, has many precursors in laboratory-developed drugs that emulate natural forms of the same drug. The policy challenges posed by synthetic artemisinin do not differ significantly in kind from other laboratory-formulated drugs. Synthetic biofuels and gene drives, however, fit less clearly into existing governance structures...
January 2018: Hastings Center Report
https://www.readbyqxmd.com/read/29452560/health-care-efficiencies-consolidation-and-alternative-models-vs-health-care-and-antitrust-regulation-irreconcilable-differences
#15
Michael W King
Despite the U.S. substantially outspending peer high income nations with almost 18% of GDP dedicated to health care, on any number of statistical measurements from life expectancy to birth rates to chronic disease, 1 the U.S. achieves inferior health outcomes. In short, Americans receive a very disappointing return on investment on their health care dollars, causing economic and social strain. 2 Accordingly, the debates rage on: what is the top driver of health care spending? Among the culprits: poor communication and coordination among disparate providers, paperwork required by payors and regulations, well-intentioned physicians overprescribing treatments, drugs and devices, outright fraud and abuse, and medical malpractice litigation...
November 2017: American Journal of Law & Medicine
https://www.readbyqxmd.com/read/29452520/the-clinical-trials-transformation-initiative-methodology-supporting-the-mission
#16
Amy Corneli, Zachary Hallinan, Gerrit Hamre, Brian Perry, Jennifer C Goldsack, Sara B Calvert, Annemarie Forrest
The mission of the Clinical Trials Transformation Initiative, a public-private partnership co-founded by the U.S. Food and Drug Administration and Duke University, is to develop and drive adoption of practices that will increase the quality and efficiency of clinical trials. The Clinical Trials Transformation Initiative works collaboratively with key stakeholders, implements "fit-for-purpose" evidence-gathering projects, and develops actionable recommendations and tools to address the challenges faced by the clinical trials enterprise...
February 2018: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/29451777/filomicelles-deliver-a-chemo-differentiation-combination-of-paclitaxel-and-retinoic-acid-that-durably-represses-carcinomas-in-liver-to-prolong-survival
#17
Praful Nair, Cory Alvey, Xiaoling Jin, Jerome Irianto, Irena Ivanovska, Dennis E Discher
Drug resistance and relapse is common in cancer treatments with chemotherapeutics, and while drug combinations with naturally occurring, differentiation-inducing retinoic acid (RA) are highly successful against one type of liquid tumor, solid tumors present major problems for delivery. Here, inspired by filoviruses that can be microns in length, flexible filomicelles that self-assemble from an amphiphilic block copolymer (PEG-PCL) are shown to effectively deliver RA and paclitaxel (TAX) to several solid tumor models, particularly in liver...
February 16, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29451063/epithelial-tumors-growing-from-within
#18
Mariana Muzzopappa, Marco Milán
The growth of epithelial tumors is often governed by cell interactions with the surrounding stroma. Drosophila has been instrumental in identifying the relevant molecular elements mediating these interactions. Of note is the role of the TNF ligand Eiger, released from recruited blood cells, in activating the JNK tumor-promoting pathway in epithelial tumors. JNK drives the transcriptional induction of mitogenic molecules, matrix metalloproteases and systemic signals that lead to tumor growth, tissue invasiveness and malignancy...
February 16, 2018: Fly
https://www.readbyqxmd.com/read/29449138/driving-with-drug-resistant-and-controlled-seizures-from-a-patient-s-perspective-assessment-of-attitudes-and-practices
#19
Lakshman Arcot Jayagopal, Kaeli K Samson, Olga Taraschenko
BACKGROUND: Driving restrictions in epilepsy are intended to safeguard public and personal safety; however, these limitations inhibit socialization, restrict employment, and reduce self-esteem in patients with seizures. A large proportion of patients with seizures continue to drive, and factors leading to noncompliance with driving regulations are poorly understood. Thus, the patients' perspective on driving safety is not incorporated into the existing counseling tools on driving safety in epilepsy...
February 12, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29448012/clogging-in-staked-in-needle-pre-filled-syringes-sin-pfs-influence-of-water-vapor-transmission-through-the-needle-shield
#20
M De Bardi, R Müller, C Grünzweig, D Mannes, M Rigollet, F Bamberg, T A Jung, K Yang
Staked-in needle pre-fillable syringes (SIN-PFS) are a convenient delivery system widely established in the growing pharmaceutical market. Under specific storage conditions, the needle of PFS containing high concentration drug product (DP) solution is prone to clogging, which prevents administration of the liquid. The purpose of this study is to clarify the clogging phenomenon of SIN-PFS and to elucidate the role of water vapor transmission via the needle shield. The presence of liquid within needles is a prerequisite condition for clogging and was investigated non-invasively by neutron imaging (NI) to confirm that liquid can migrate into the needle under certain processing conditions...
February 12, 2018: European Journal of Pharmaceutics and Biopharmaceutics
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