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https://www.readbyqxmd.com/read/28528519/il-6-blockade-in-the-management-of-non-infectious-uveitis
#1
Giuseppe Lopalco, Claudia Fabiani, Jurgen Sota, Orso Maria Lucherini, Gian Marco Tosi, Bruno Frediani, Florenzo Iannone, Mauro Galeazzi, Rossella Franceschini, Donato Rigante, Luca Cantarini
Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases...
May 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28528302/nanomolar-anti-sickling-compounds-identified-by-ligand-based-pharmacophore-approach
#2
Odailson Santos Paz, Milena de Jesus Pinheiro, Renan Fernandes do Espirito Santo, Cristiane Flora Villarreal, Marcelo Santos Castilho
Adenosine receptors are considered as potential targets for drug development against several diseases. The discovery of subtype 2B adenosine receptors role in erythrocyte sickling process proved its importance to neglected diseases such as sickle cell anemia, which affects approximately 29.000 people around the world, but whose treatment is restricted to just one FDA approved drug (hydroxyurea). In order to widen the therapeutic arsenal available to treat sickle cell anemia patients, it is imperative to identify new lead compounds that modify the sickling course and not just its symptoms...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528297/biogenic-aldehydes-as-therapeutic-targets-for-cardiovascular-disease
#3
REVIEW
Margaret-Ann M Nelson, Shahid P Baba, Ethan J Andersonc
Aldehydes are continuously formed in biological systems through enzyme-dependent and spontaneous oxidation of lipids, glucose, and primary amines. These highly reactive, biogenic electrophiles can become toxic via covalent modification of proteins, lipids and DNA. Thus, agents that scavenge aldehydes through conjugation have therapeutic value for a number of major cardiovascular diseases. Several commonly-prescribed drugs (e.g., hydralazine) have been shown to have potent aldehyde-conjugating properties which may contribute to their beneficial effects...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28528284/biomarkers-in-epilepsy-a-modelling-perspective
#4
Sven C van Dijkman, Rob A Voskuyl, Elizabeth C de Lange
Biomarkers can be categorised from type 0 (genotype or phenotype), through 6 (clinical scales), each level representing a part of the processes involved in the biological system and drug treatment. This classification facilitates the identification and connection of information required to fully (mathematically) model a disease and its treatment using integrated information from biomarkers. Two recent reviews thoroughly discussed the current status and development of biomarkers for epilepsy, but a path towards the integration of such biomarkers for the personalisation of anti-epileptic drug treatment is lacking...
May 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28527822/synthesis-and-biological-evaluation-of-new-c-12-%C3%AE-%C3%AE-n-sulfamoyl-phenylamino-14-deoxy-andrographolide-derivatives-as-potent-anti-cancer-agents
#5
Sai Giridhar Sarma Kandanur, Srinivas Nanduri, Nageswara Rao Golakoti
Andrographolide, the major diterpenoidal constituent of Andrographis paniculata (Acanthaceae) and its derivatives have been reported to possess plethora of biological properties including potent anti-cancer activity. In this work, synthesis and in-vitro anti-cancer evaluation of new C-12-substituted aryl amino 14-deoxy-andrographolide derivatives (III a-f) are reported. The substitutions include various sulfonamide moieties -SO2-NH-R(1). The new derivatives (III a-e) exhibited improved cytotoxicity (GI50, TGI and LC50) compared to andrographolide (I) and the corresponding 3,14,19-O-triacetyl andrographolide (II) when evaluated against 60 NCI cell line panel...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28527736/the-effects-of-non-invasive-radiofrequency-electric-field-hyperthermia-on-biotransport-and-biodistribution-of-fluorescent-60-fullerene-derivative-in-a-murine-orthotopic-model-of-breast-adenocarcinoma
#6
Norman A Lapin, Martyna Krzykawska-Serda, Sean Dilliard, Yuri Mackeyev, Maciej Serda, Lon J Wilson, Steven A Curley, Stuart J Corr
The aim of this study is to understand the combined and differential biokinetic effects of radiofrequency (RF) electric-field hyperthermia as an adjunctive therapy to [60]fullerene nanoparticle-based drug delivery systems in targeting the micro-vasculature and micro-environments of breast cancer tumors. Intravital microscopy (IVM) is an ideal tool to provide the spatial and temporal resolution needed for quantification in this investigation. The water-soluble and fluorescent [60]fullerene derivative (C60-serPF) was designed to be an amphiphilic nanostructure, which is able to cross several biological membranes and accumulate in tumor tissues by passing through abnormally leaky tumor blood vessels...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28527344/harnessing-plant-metabolic-diversity
#7
REVIEW
Charlie Owen, Nicola J Patron, Ancheng Huang, Anne Osbourn
Advances in DNA sequencing and synthesis technologies in the twenty-first century are now making it possible to build large-scale pipelines for engineering plant natural product pathways into heterologous production species using synthetic biology approaches. The ability to decode the chemical potential of plants by sequencing their transcriptomes and/or genomes and to then use this information as an instruction manual to make drugs and other high-value chemicals is opening up new routes to harness the vast chemical diversity of the Plant Kingdom...
May 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28527094/circulating-tumor-dna-measurement-by-picoliter-droplet-based-digital-pcr-and-vemurafenib-plasma-concentrations-in-patients-with-advanced-braf-mutated-melanoma
#8
Fanny Garlan, Benoit Blanchet, Nora Kramkimel, Alicja Puszkiel, Jean-Louis Golmard, Gaelle Noe, Nicolas Dupin, Pierre Laurent-Puig, Michel Vidal, Valerie Taly, Audrey Thomas-Schoemann
BACKGROUND: Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. OBJECTIVE: We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. PATIENTS AND METHODS: Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study...
May 19, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28526943/a-global-reference-comparator-for-biosimilar-development
#9
Christopher J Webster, Gillian R Woollett
Major drug regulators have indicated in guidance their flexibility to accept some development data for biosimilars generated with reference product versions licensed outside their own jurisdictions, but most authorities require new bridging studies between these versions and the versions of them licensed locally. The costs of these studies are not trivial in absolute terms and, due to the multiplier effect of required repetition by each biosimilar sponsor, their collective costs are substantial. Yet versions of biologics licensed in different jurisdictions usually share the same development data, and any manufacturing changes between versions have been justified by a rigorous comparability process...
May 19, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28526922/advances-in-systemic-therapy-for-metastatic-breast-cancer-future-perspectives
#10
REVIEW
S P Corona, N Sobhani, A Ianza, G Roviello, G Mustacchi, M Bortul, F Zanconati, D Generali
Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28526769/tam-receptor-tyrosine-kinases-in-cancer-drug-resistance
#11
REVIEW
Mikaella Vouri, Sassan Hafizi
Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526743/systematic-identification-of-functional-residues-of-artemisia-annua-amorpha-4-11-diene-synthase
#12
Xin Fang, Jian-Xu Li, Jin-Quan Huang, You-Li Xiao, Peng Zhang, Xiao-Ya Chen
Terpene synthases (TPSs) are responsible for the extremely diversified and complex structure of terpenoids. Amorpha-4,11-diene synthase (ADS) has a high (90%) fidelity in generating the sesquiterpene precursor for biosynthesis of artemisinin, an antimalarial drug, however, little is known about how active site residues of ADS involved in the carbocation rearrangement and cyclization reactions. Here, we identify seven residues that are key to most of the catalytic steps in ADS. By structural modeling and amino acid sequence alignments of ADS with two functionally relevant sesquiterpene synthases from Artemisia annua, we performed site-directed mutagenesis and found that a single substitution, T296V, impaired the ring closure activity almost completely, and tetra-substitutions (L374Y/L404V/L405I/G439S) led to an enzyme generating 80% monocyclic bisabolyl-type sesquiterpenes, whereas a double mutant (T399L/T447G) showed compromised activity in regioselective deprotonation to yield 34...
May 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28526658/nonclinical-pharmacology-and-toxicology-of-the-first-biosimilar-insulin-glargine-drug-product-basaglar-%C3%A2-abasaglar-%C3%A2-approved-in-the-european-union
#13
Richard A Byrd, Rebecca A Owens, Jamie L Blackbourne, David E Coutant, Mark W Farmen, M Dodson Michael, Julie S Moyers, A Eric Schultze, Michael K Sievert, Niraj K Tripathi, John L Vahle
Basaglar(®)/Abasaglar(®) (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus(®) (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity...
May 16, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28526555/modeling-psychomotor-retardation-using-ipscs-from-mct8-deficient-patients-indicates-a-prominent-role-for-the-blood-brain-barrier
#14
Gad D Vatine, Abraham Al-Ahmad, Bianca K Barriga, Soshana Svendsen, Ariel Salim, Leslie Garcia, Veronica J Garcia, Ritchie Ho, Nur Yucer, Tongcheng Qian, Ryan G Lim, Jie Wu, Leslie M Thompson, Weston R Spivia, Zhaohui Chen, Jennifer Van Eyk, Sean P Palecek, Samuel Refetoff, Eric V Shusta, Clive N Svendsen
Inactivating mutations in the thyroid hormone (TH) transporter Monocarboxylate transporter 8 (MCT8) cause severe psychomotor retardation in children. Animal models do not reflect the biology of the human disease. Using patient-specific induced pluripotent stem cells (iPSCs), we generated MCT8-deficient neural cells that showed normal TH-dependent neuronal properties and maturation. However, the blood-brain barrier (BBB) controls TH entry into the brain, and reduced TH availability to neural cells could instead underlie the diseased phenotype...
May 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28526399/evaluation-of-the-effectiveness-of-chronic-antidepressant-drug-treatments-in-the-hippocampal-mitochondria-a-proteomic-study-in-an-animal-model-of-depression
#15
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Rafał Olszanecki, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
Several lines of evidence indicate that adverse experience in early life may be a triggering factor for disturbances in the brain mitochondrial proteins and lead to the development of depression in adulthood. On the other hand, little is known about the impact of chronic administration of various antidepressant drugs on the brain mitochondria, as a target for the pharmacotherapy of depression. The purpose of our study was to compare the impact of chronic treatment with two antidepressant drugs with different mechanisms of action, a tricyclic antidepressant (TCA), imipramine, and an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, fluoxetine, on the mitochondria-enriched subproteome profile in the hippocampus of 3-month-old male rats following a prenatal stress procedure (an animal model of depression)...
May 16, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28526123/-direct-mechanism-of-action-in-toxic-myopathies
#16
REVIEW
A Khelfi, M Azzouz, R Abtroun, M Reggabi, B Alamir
Toxic myopathies are a large group of disorders generated by surrounding agents and characterized by structural and/or functional disturbances of muscles. The most recurrent are those induced by commonly used medications. Illicit drugs, environmental toxins from animals, vegetables, or produced by micro-organisms as well as chemical products commonly used are significant causes of such disorders. The muscle toxicity results from multiple mechanisms at different biological levels. Many agents can induce myotoxicity through a direct mechanism in which statins, glucocorticoids and ethyl alcohol are the most representative...
May 16, 2017: Annales Pharmaceutiques Françaises
https://www.readbyqxmd.com/read/28525957/determining-dominant-driving-forces-affecting-controlled-protein-release-from-polymeric-nanoparticles
#17
Josh Smith, Kayla G Sprenger, Rick Liao, Andrea Joseph, Elizabeth Nance, Jim Pfaendtner
Enzymes play a critical role in many applications in biology and medicine as potential therapeutics. One specific area of interest is enzyme encapsulation in polymer nanostructures, which have applications in drug delivery and catalysis. A detailed understanding of the mechanisms governing protein/polymer interactions is crucial for optimizing the performance of these complex systems for different applications. Using a combined computational and experimental approach, this study aims to quantify the relative importance of molecular and mesoscale driving forces to protein release from polymeric nanoparticles...
May 19, 2017: Biointerphases
https://www.readbyqxmd.com/read/28525889/eugenol-alleviated-breast-precancerous-lesions-through-her2-pi3k-akt-pathway-induced-cell-apoptosis-and-s-phase-arrest
#18
Min Ma, Yi Ma, Gui-Juan Zhang, Rui Liao, Xue-Feng Jiang, Xian-Xin Yan, Feng-Jie Bie, Xiao-Bo Li, Yan-Hong Lv
Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525781/sleep-waves-and-recovery-from-drug-and-alcohol-dependence-towards-a-rhythm-analysis-of-sleep-in-residential-treatment
#19
Robert Meadows, Sarah Nettleton, Joanne Neale
This paper reports on a study of sleep amongst men and women who are living in residential rehabilitation centres in the UK and who are receiving support for their recovery from addiction to alcohol and other forms of substance use. Conceptually and methodologically, the paper draws on the work of the French sociologist Lefebvre and, in particular, his rhythmanalysis. We argue that this approach offers a useful way of exploring sleep in terms of biological, experiential, temporal, spatial and social rhythms...
May 6, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28525765/covalent-probe-finds-carboxylic-acid
#20
Alexander Jones, Xiaoyun Zhang, Xiaoguang Lei
In this issue of Cell Chemical Biology, Martín-Gago et al. (2017a) disclose a new strategy for the selective covalent targeting of binding site carboxylic acids within the proteome using the isoxazolium salt as a warhead. This discovery paves the way for developing new protein ligation methods as well as covalent drug candidates.
May 18, 2017: Cell Chemical Biology
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