5,400,849 results match your criteria Drug Discovery Today incorporating Pharmaceutical Science and Technology Today[Journal]
Duke Law J 2018 Dec;68(3):417-78
Three widely discussed explanations of the punitive carceral state are racism, harsh drug laws, and prosecutorial overreach. These three narratives, however, only partially explain how our correctional system expanded to its current overcrowded state. Neglected in our discussion of mass incarceration is our largely forgotten history of the long-term, wholesale institutionalization of the disabled. Read More
Fed Regist 2018 Dec;83(241):64443-58
The Food and Drug Administration (FDA, the Agency, or we) is issuing a final rule to amend its regulations governing classification and reclassification of medical devices to conform to the applicable provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA). FDA is also making additional changes unrelated to the FDASIA requirements, to update its regulations governing the classification and reclassification of medical devices. FDA is taking this action to codify the procedures and criteria that apply to the classification and reclassification of medical devices and to provide for classification of devices in the lowest regulatory class consistent with the public health and the statutory scheme for device regulation. Read More
Semin Dial 2018 Dec 17. Epub 2018 Dec 17.
Departments of Medicine and Surgery, Yale University, New Haven, Connecticut.
Hepatitis C direct acting antiviral (DAA) therapy has evolved so that infected patients with advanced chronic kidney disease (CKD) can now anticipate the opportunity for sustained virologic response equivalent to that of the broader population of patients with hepatitis C. This has revolutionized the field of transplantation as it relates to renal transplant candidates with hepatitis C and the use of grafts from hepatitis C virus (HCV) viremic donors. In treating this population of patients, special consideration must be given to the timing of anti-viral therapy and drug-drug interactions. Read More
Cell Physiol Biochem 2018 Dec 17;51(6):2509-2522. Epub 2018 Dec 17.
Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou,
Background/aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines.
Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods. Read More
Nanotechnology 2018 Dec 17. Epub 2018 Dec 17.
Materials Science&Engineering, East China University of Science and Technology, No.130, Meilong Rd, Xuhui District, Shanghai, Shanghai, 200237, CHINA.
Although the special architecture of two-dimensional (2D) nanomaterials endows them with unique properties, their poor colloidal stability remains a main bottleneck to fully exploit their applications in the biomedical field. Herein, this study aims to develop a simple and effective approach to in situ incorporate 2D graphene oxide (GO) nanopletlets into thermosensitive matrix to acquire hybrid nanogels with good stability and photothermal effect. In order to improve its stability, GO firstly underwent silanization to its surface with double bonds, followed by intercalation with N-isopropylacrylamide (NIPAM) in the presence of disulfide-containing crosslinker via an emulsion method. Read More
Phys Biol 2018 Dec 17. Epub 2018 Dec 17.
Department of Bioengineering, Rice University, 6100 Main Street, MS-142, Houston, TX 77251-1892, USA, Houston, Texas, UNITED STATES.
The epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis and drug resistance - two persistent clinical challenges. Epithelial cells can undergo a partial or full EMT, attaining either a hybrid epithelial/mesenchymal (E/M) or mesenchymal phenotype, respectively. Recent studies have emphasized that hybrid E/M cells may be more aggressive than their mesenchymal counterparts. Read More
Endocr Connect 2018 Dec 1. Epub 2018 Dec 1.
Z Wang, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Angiogenesis has a pivotal role in the growth and metastasis of pancreatic neuroendocrine tumors (PNETs). Apatinib inhibits angiogenesis as a highly selective VEGFR2 inhibitor and has been used to treat advanced gastric cancer and malignancies in clinical settings. However, the efficacy of apatinib in PNETs remains unclear. Read More
Biomed Pharmacother 2018 Dec 14;110:857-868. Epub 2018 Dec 14.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:
Invasive candidiasis (IC) can affect individuals with various underlying diseases hospitalized in different parts of hospitals. In recent decades, IC has caused 27-55% mortality in general population. Although Candida albicans (C. Read More
Biomed Pharmacother 2018 Dec 14;110:834-843. Epub 2018 Dec 14.
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China. Electronic address:
Objective: CP-25 attenuates arthritis progression in animal models by inhibiting G protein-coupled receptor kinase 2 (GRK2) membrane expression. This study compared groups treated with high-dose methotrexate (MTX)/leflunomide (LEF) and CP-25 combined with low-dose MTX/LEF in an adjuvant-induced arthritis (AA) rat model and investigated possible mechanisms.
Methods: AA was induced in rats via complete Freund's adjuvant. Read More
Eur J Med Chem 2018 Dec 4;163:583-596. Epub 2018 Dec 4.
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, 100191, Haidian District, Beijing, China. Electronic address:
Sulfated hyaluronic acid (sHA) is chemically synthetic mimetic of glycosaminoglycan (GAG) presenting promising biological functions. Specific sulfation pattern, termed as sulfation code plays critical roles in regulating the binding mode between GAG and proteins. As a structural analogue of chondroitin sulfate (CS), sHA bears much higher molecular weight and is nearly free of other proteoglycan contaminants. Read More
Forensic Sci Int 2018 Dec 6;295:36-45. Epub 2018 Dec 6.
Jagiellonian University, Faculty of Chemistry, Gronostajowa 2, 30-387 Kraków, Poland.
Introduction: Although there is an observed decline in the number of new psychoactive substances entering the drug market, this phenomenon is still a significant public health problem. Synthetic cathinones are the second largest group of new substances and currently belong to the most frequently confiscated. Their availability and prevalence cause that they are often abused. Read More
Comput Biol Chem 2018 Dec 7;78:190-204. Epub 2018 Dec 7.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address:
Background: Phosphoinositide-3-kinase Delta (PI3Kδ) plays a key role in B-cell signal transduction and inhibition of PI3Kδ is confirmed to have clinical benefit in certain types of activation of B-cell malignancies. Virtual screening techniques have been used to discover new molecules for developing novel PI3Kδ inhibitors with little side effects.
Method: Computer aided drug design method were used to rapidly screen optimal PI3Kδ inhibitors from the Asinex database. Read More
Comput Biol Chem 2018 Nov 27;78:178-189. Epub 2018 Nov 27.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China. Electronic address:
PPARα and PPARγ play an important role in regulating glucose and lipid metabolism. The single and selective PPARα or PPARγ agonists have caused several side effects such as edema, weight gain and cardiac failure. In the recent years, the dual PPARs agonist development has become a hot topic in the antidiabetic medicinal chemistry field. Read More
Drug Alcohol Depend 2018 Dec 8;195:6-12. Epub 2018 Dec 8.
Recovery Research Institute, Massachusetts General Hospital and Harvard Medical School, 151 Merrimac Street, Boston, MA, 02114, USA.
Background: Tobacco and alcohol and other drug (AOD) use remain prominent risk factors for morbidity, mortality, and health care utilization. Moreover, these often cluster together within persons, exponentiating health risks. Little is known regarding if and when people resolving AOD problems stop smoking, who stops, and whether recent general population trends toward smoking cessation are evident also among persons more recently entering recovery. Read More
Drug Alcohol Depend 2018 Dec 4;195:13-15. Epub 2018 Dec 4.
Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY, United States.
Objectives: To characterize the socio-demographic characteristics, medical conditions, and psychiatric comorbidities of users of marijuana for medical and non-medical purposes.
Methods: Data were from the National Epidemiological Survey on Alcohol and Related Conditions III, a US nationally representative in-person interview of 36,309 adults age ≥18 years in 2012-2013.
Results: In relation to non-medical only users (n = 3339), combined (n = 362) and medical only (n = 82) users had higher prevalence of every medical condition examined. Read More
J Photochem Photobiol B 2018 Nov 20;191:1-5. Epub 2018 Nov 20.
The Third Department of Tumor Surgery, Tangshan Gongren Hospital, People's Republic of China. Electronic address:
Sorafenib (SRF) is a well-known tyrosine kinase inhibiting anticancer drug which iseffectual against multiple carcinomas especially gastric cancers by targeting the Ras/Raf/Mek/Erk cascade pathway and blocking the tumor cell proliferation. In the present work, we have reduced graphene oxide (GO) in presence of sorafenib using ascorbic as green reducing agent for the treatment of gastric cancers. Sorafenib reduced graphene oxide (SRGO) were obtained with a transparent and smoothmorphology. Read More
J Allergy Clin Immunol Pract 2018 Dec 14. Epub 2018 Dec 14.
Department of Allergy, Kaiser Permanente Southern California, San Diego, CA; Department Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA.
A large number of clinically impactful studies and reviews were published in this Journal in 2018. This article provides highlights of the original research published in 2018 issues of JACI: In Practice on the subjects of anaphylaxis, asthma, dermatitis, drug allergy, eosinophilic disorders, food allergy, immune deficiency, rhinitis/upper respiratory disease, and urticaria/angioedema. Within each topic, practical aspects of diagnosis and management are emphasized. Read More
J Allergy Clin Immunol Pract 2018 Dec 14. Epub 2018 Dec 14.
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address:
Hemophagocytic lymphohistiocytosis (HLH) is an overwhelming clinical syndrome associated with extreme immune activation. Familial HLH is caused by autosomal recessive inheritance of gene mutations that cripple lymphocyte cytotoxicity. X-linked lymphoproliferative diseases and mutations in NLRC4 also feature HLH as a predominant manifestation. Read More
J Psychiatr Res 2018 Dec 10;109:193-201. Epub 2018 Dec 10.
University of Queensland, School of Medicine, Brisbane, Australia; Metro South Addiction and Mental Health Service, Brisbane, Australia.
Dosing regimens for depot antipsychotics range from two-to twelve-weekly administration. There are limited meta-analytic data regarding the effect of different injection frequencies of the same depot antipsychotic at the equivalent dose on psychiatric outcomes and adverse effects. This study investigated differences in psychiatric outcomes and adverse effects between different frequencies of depot antipsychotics through a systematic review and meta-analysis. Read More
Acta Biomater 2018 Dec 14. Epub 2018 Dec 14.
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, PR China. Electronic address:
In this study, an AIE-active polymer (FTP) was successfully prepared and employed to load anti-cancer drug doxorubicin (DOX) for self-indicating cancer therapy via dual FRET process. Our results demonstrated that the FTP polymer could self-assemble into nanoparticles (NPs) in aqueous solutions to give strong fluorescence emission via intramolecular FRET process. The DOX loaded FTP NPs (drug loading content: 21. Read More
Int J Pharm 2018 Dec 14. Epub 2018 Dec 14.
Department of Hematology and Research Laboratory of Hematology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center, Chengdu, 610041, PR China. Electronic address:
Drug resistance and recurrence are the main clinical challenges in chemotherapy of lymphoma. Methotrexate (MTX), especially high dose MTX (HD MTX), is extensively used to treat some aggressive subtypes of lymphoma, such as Burkitt's lymphoma, in order to overcome drug resistance. But poor solubility of the free drug and severe side effects of HD MTX limit its clinical application. Read More
Int J Pharm 2018 Dec 14. Epub 2018 Dec 14.
Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China.
Nanocrystals has been constructed for insoluble drugs as a novel type of nanoscale drug delivery systems with high drug loading. How to prepare nanocrystals with good stability and tumor targeting capability is still challenging. This study was to modify paclitaxel nanocrystals with polyethylene glycol (PEG) for stabilization and RGD peptide for tumor targeting. Read More
Int J Pharm 2018 Dec 14. Epub 2018 Dec 14.
School of Pharmacy, University of East Anglia, Norwich NR7 1AT, UK. Electronic address:
This study describes the preparation of free films of zein with and without acetylated high amylose maize starch (HAS) and their corresponding coated tablets as a novel approach to colonic drug delivery. We hypothesise that the embedding of a digestible starch component within the inert zein would allow the film to remain intact until the large intestine is reached. Free films of zein alone and starch/zein were prepared and characterised. Read More
Int J Radiat Oncol Biol Phys 2018 Dec 14. Epub 2018 Dec 14.
Centre for Cancer Research & Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7AE, United Kingdom.
Introduction: Despite the effectiveness of RaCl for treating patients with symptomatic bone metastatic disease, its mechanisms of action are still unclear. Even established dosimetric approaches differ considerably in their conclusions. In silico tumour models bring a new perspective to this as they can quantitatively simulate the interaction of α-particles with the target(s). Read More
Food Chem Toxicol 2018 Dec 14. Epub 2018 Dec 14.
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building, Biocant Park, 3060-197, Cantanhede, Portugal. Electronic address:
Dose-dependent and cumulative cardiotoxicity associated with doxorubicin (DOX) is the main limitation of anticancer therapy. Pediatric cancer survivors are particularly vulnerable, and no effective prevention measures are available. The aim of the present study was to investigate the persistent effects of nanomolar DOX concentrations and determine whether a pretreatment would induce mitochondrial adaptations in H9c2 cardiomyoblasts. Read More
Drug Discov Today 2018 Dec 14. Epub 2018 Dec 14.
Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi-110062, India. Electronic address:
In recent decades, extensive emphasis has been given on developing nanopharmaceutical products for improving the therapeutic performance of drugs, resulting in an increasing number of product approvals by drug regulatory agencies. Although nanopharmaceuticals are subjected to the same regulatory pathways as conventional pharmaceutical products, their biopharmaceutical characteristics at the nanoscale make them vulnerable to high variability in quality. Positive effects on drug quality assurance have resulted from adopting systematic quality-by-design (QbD) principles, boosting pharmaceutical manufacturing with improvements in the quality, safety, and efficacy of drugs. Read More
J Control Release 2018 Dec 14. Epub 2018 Dec 14.
Department of Oncology and Hemato-Oncology, Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy. Electronic address:
Extracellular vesicles (EVs), are naturally occurring cargo delivery tools with the potential to be used as drug vehicles of single agents or combination therapies. We previously demonstrated that human lung cancer cell-derived EVs could be used for the systemic delivery of oncolytic virus (OVs) and chemotherapy drugs such as paclitaxel (PTX), leading to enhanced anti-tumor effects in nude mice. In the current work, we evaluated the biodistribution of EVs by using bioluminescence and fluorescence imaging technologies, thus proving the ability of these EVs-formulations to specifically target the neoplasia, while leaving other body tissues unaffected. Read More
Int J Biol Macromol 2018 Dec 14. Epub 2018 Dec 14.
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, India. Electronic address:
The aim of present study is to browse mucoadhesive potential of flaxseed mucilage after thiol functionalization. Thiol-derivatization of flaxseed mucilage (FSM) polysaccharide was obtained by esterification with thioglycolic acid. Thiolation of FSM was confirmed by -SH stretch in FTIR spectra at 2549. Read More
Pharmacol Ther 2018 Dec 14. Epub 2018 Dec 14.
University of Washington, School of Pharmacy, Department of Pharmaceutics, Seattle, WA, USA. Electronic address:
The importance of uptake transporters in determining drug disposition is increasingly appreciated. While the focus of regulatory agencies worldwide has been on the hepatic organic anion transporting polypeptides (OATPs) 1B1 and 1B3, there is another isoform of the OATP sub-family, OATP2B1, which should be considered equally relevant. Unlike the other members of the OATP sub-family, OATP2B1 is expressed in multiple organs in humans, including in the intestine and the liver. Read More
Int J Biochem Cell Biol 2018 Dec 14. Epub 2018 Dec 14.
Laboratory for Cancer Biology, Department of Medical Oncology and Clinical Research, Cancer Institute (WIA), Chennai, India. Electronic address:
Induced pluripotent stem cells are derived from adult somatic cells by ectopic expression of stem cell factors OCT4, SOX2, MYC and KLF4. These cells have characteristic features similar to embryonic stem cells. Although there exists in vitro and in vivo models of cancer, recapitulating the earliest events in the pathogenesis remain challenging. Read More
Int J Biochem Cell Biol 2018 Dec 14. Epub 2018 Dec 14.
Center of Physiology and Pharmacology, Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Waehringerstrasse 13a, 1090 Vienna, Austria. Electronic address:
Several shortcomings with currently available pharmacotherapy of epilepsy necessitate the search for new drug targets. Paroxysmal depolarization shifts (PDS) represent the cellular correlates of electrographic (e.g. Read More
Eur J Pharm Sci 2018 Dec 14. Epub 2018 Dec 14.
School of Pharmaceutical Sciences, Zhengzhou University, No.100. Kexue Road, Zhengzhou, Henan Province 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, China. Electronic address:
We recently reported that the absolute oral bioavailability of flavonoid Morin was extremely low at 0.45%, resulting in unsatisfied therapeutic efficacy in vivo. The present study was aimed to systemically assess the pre-absorption risks of Morin for rationale formulation design. Read More
Toxicol Lett 2018 Dec 14. Epub 2018 Dec 14.
Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain.
Neurochem Int 2018 Dec 14. Epub 2018 Dec 14.
NIDA Intramural Program, Molecular Neuropsychiatry Research Branch, 251 Bayview Boulevard, Baltimore, MD, 21224, USA. Electronic address:
Although some of the clinical manifestations of substance use disorders might be superficially similar, it is highly likely that different classes of abused drugs including opioids (heroin, morphine, and oxycodone, other opioids) and psychostimulants (cocaine and amphetamines) cause different neuroadaptations in various brain regions dependent in the distribution and concentration of their biochemical sites of actions. In fact, different molecular networks are indeed impacted by acute and chronic administration of addictive substances. Some of the genes whose expression is influenced by the administration of these substances are immediate-early genes (IEGs). Read More
Peptides 2018 Dec 14. Epub 2018 Dec 14.
Department of Neuroscience, School of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Effective management of chronic pain is demanded by ethical as well as medical considerations. Although opioid analgesics remain among the most effective pharmacotherapies for ameliorating many types of pain, their use is clouded by concerns regarding their addictive properties, underscored by the current epidemic of prescription opioid abuse and attendant deaths. Medicinal harnessing of endogenous opioid antinociception could provide a strategy for continuing to take advantage of the powerful antinociceptive properties of opioids while avoiding their abuse potential. Read More
Dev Comp Immunol 2018 Dec 14. Epub 2018 Dec 14.
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China. Electronic address:
Mitochondrial antiviral-signaling protein (MAVS) is an essential adaptor protein in retinoic acid-inducible gene I (RIG-I)-mediated antiviral innate immunity in mammals. In this study, the goose MAVS gene (goMAVS) was identified. The 2,019 bp-long goMAVS exhibits 96. Read More
Behav Brain Res 2018 Dec 14. Epub 2018 Dec 14.
Department of Neurobiology & Anatomy, University of Texas McGovern Medical School, Houston, TX 77030 United States.
Attention Deficit Hyperactivity Disorder (ADHD) is a developmental, behavioral disorder that is characterized by patterns of impulsivity and limited attention. Stimulants, such as methylphenidate (MPD) and amphetamine (Amph), are utilized as first-line agents in the treatment of ADHD. While Amph is known elicit dependence, MPD is not. Read More
Antiviral Res 2018 Dec 14. Epub 2018 Dec 14.
Aix-Marseille Université, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 163 avenue de Luminy, 13288, Marseille, France. Electronic address:
Arenaviridae is a viral family whose members are associated with rodent-transmitted infections to humans responsible of severe diseases. The current lack of a vaccine and limited therapeutic options make the development of efficacious drugs of high priority. The cap-snatching mechanism of transcription of Arenavirus performed by the endonuclease domain of the L-protein is unique and essential, so we developed a drug design program targeting the endonuclease activity of the prototypic Lymphocytic ChorioMeningitis Virus. Read More
Exp Neurol 2018 Dec 14. Epub 2018 Dec 14.
Department of Pharmacology and Toxicology, University of Kansas, 5064 Malott Hall, 1251 Wescoe Hall Dr., Lawrence, KS 66045, USA. Electronic address:
Neuronal mitochondrial dysfunction and oxidative stress are key pathophysiologic mechanisms of diabetic peripheral neuropathy (DPN). KU-596 is a small molecule modulator of heat shock protein 90 (Hsp90) that can reverse clinically relevant measures of DPN in diabetic animal models. Mechanistically, drug efficacy requires Hsp70 and correlates with improving mitochondrial maximal respiratory capacity (MRC) and decreasing oxidative stress in diabetic sensory neurons. Read More
J Pharm Sci 2018 Dec 14. Epub 2018 Dec 14.
QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address:
Montelukast (MLK), an oral anti-asthmatic drug with growing use, requires special care in formulation and storage to avoid its degradation by action of light and/or water. This work investigates the increase in the stability of montelukast as the effect of molecular encapsulation with gamma-cyclodextrin (γ-CD) by means of a solvent-free method, co-grinding. As a first step, a 1:1 preferred stoichiometry is established for this host-guest system using a combination of molecular modelling and the continuous variation method. Read More
Eur J Pharmacol 2018 Dec 14. Epub 2018 Dec 14.
I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St.Petersburg 194223, Russia.
Hydrophobic monoamines containing only a hydrophobic/aromatic moiety and protonated amino group are a recently described class of acid-sensing ion channel (ASIC) modulators. Intensive studies have revealed a number of active compounds including endogenous amines and pharmacological agents and shown that these compounds potentiate and inhibit ASICs depending on their specific structure and on subunit composition of the target channel. The action of monoamines also depends on the application protocol, membrane voltage, conditioning and activating pH, suggesting complex mechanism(s) of the ligand-receptor interaction. Read More
Biochem Pharmacol 2018 Dec 14. Epub 2018 Dec 14.
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52 D-20246 Hamburg, Germany. Electronic address:
The inositol phosphates, InsP and InsP, have recently been identified as binding partners of fibrinogen, which is critically involved in hemostasis by crosslinking activated platelets at sites of vascular injury. Here, we investigated the putative physiological role of this interaction and found that platelets increase their InsP concentration upon stimulation with the PLC-activating agonists thrombin, collagen I and ADP and present a fraction of it at the outer plasma membrane. Cone and plate analysis in whole blood revealed that InsP specifically increases platelet aggregate size. Read More
J Clin Oncol 2018 Dec 13:JCO1801457. Epub 2018 Dec 13.
Dana-Farber Cancer Institute, Boston, MA.
Purpose: Anti-CD19-directed chimeric antigen receptor (CAR) T-cell therapy has had a resounding effect on the treatment of chemotherapy-insensitive aggressive B-cell non-Hodgkin lymphoma (B-NHL). There are now two US Food and Drug Administration (FDA)-approved products available for treating these patients, and a third product is expected to be approved in the coming months. The question remains: Is there a preferred or best product for my patient? However, answering that question is more complicated than simply balancing the reported efficacy and toxicity results. Read More
Bioconjug Chem 2018 Dec 17. Epub 2018 Dec 17.
A bio-reducible poly(disulfide)-derived amphiphilic block copolymer-drug conjugate (loading content 31 %) was synthesized by post-polymerization modification. It shows redox-responsive polymersome assembly in water with aggregation induced emission property arising from the appended Camptothecin (CPT) drug. Glutathione (GSH), a tri-peptide over-expressed in cancer cell, triggers a cascade reaction resulting in simultaneous degradation of the polymer backbone (consisting of disulfide linkage) and the release of the pendant drug. Read More
ACS Nano 2018 Dec 17. Epub 2018 Dec 17.
Using coarse-grained molecular dynamics simulations, we systematically investigate the receptor-mediated endocytosis of elastic nanoparticles (NPs) with different sizes, ranging from 25 nm to 100 nm, and shapes, including sphere-like, oblate-like and prolate-like. Simulation results provide clear evidence that the membrane wrapping efficiency of NPs during endocytosis is a result of competition between receptor diffusion kinetics and thermodynamic driving force. The receptor diffusion kinetics refer to the kinetics of receptor recruitment that are affected by the contact edge length between the NP and membrane. Read More
J Org Chem 2018 Dec 17. Epub 2018 Dec 17.
A robust process to manufacture AMG 232 was developed to deliver drug substance of high purity. Highlights of the commercial process development efforts include: i. use of a novel bench-stable Vilsmeier reagent, methoxymethylene-N,N-dimethyliminium methyl sulfate, for selective in situ activation of a primary alcohol intermediate; ii. Read More
J Am Chem Soc 2018 Dec 17. Epub 2018 Dec 17.
Cells use membrane proteins as gatekeepers to transport ions and molecules, catalyze reactions, relay signals, and interact with other cells. DNA nanostructures with lipidic anchors are promising as membrane protein mimics because of their high tuneability. However, the design features specifying DNA nanostructure's functions in lipid membranes are yet to be fully understood. Read More
Ann Intern Med 2018 Dec 18. Epub 2018 Dec 18.
Weill Cornell Medical College, New York, New York (S.M.M., J.A.L., P.J.J., B.R.S.).
Background: Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder.
Objective: To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone.
Design: Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U. Read More
PLoS One 2018 17;13(12):e0209162. Epub 2018 Dec 17.
Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Saga, Japan.
A major challenge in cardiac tissue engineering is the host's immune response to artificial materials. To overcome this problem, we established a scaffold-free system for assembling cell constructs using an automated Bio-3D printer. This printer has previously been used to fabricate other three-dimensional (3D) constructs, including liver, blood vessels, and cartilage. Read More
PLoS One 2018 17;13(12):e0209150. Epub 2018 Dec 17.
Service d'Etude des Prions et Infections Atypiques (SEPIA), Institut François Jacob, CEA, Université Paris-Saclay, Fontenay-aux-Roses, France.
Human mini-brains (MB) are cerebral organoids that recapitulate in part the complexity of the human brain in a unique three-dimensional in vitro model, yielding discrete brain regions reminiscent of the cerebral cortex. Specific proteins linked to neurodegenerative disorders are physiologically expressed in MBs, such as APP-derived amyloids (Aβ), whose physiological and pathological roles and interactions with other proteins are not well established in humans. Here, we demonstrate that neuroectodermal organoids can be used to study the Aβ accumulation implicated in Alzheimer's disease (AD). Read More