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https://www.readbyqxmd.com/read/30551159/elagolix-for-endometriosis-all-that-glitters-is-not-gold
#1
Paolo Vercellini, Paola Viganò, Giussy Barbara, Laura Buggio, Edgardo Somigliana
Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu...
December 14, 2018: Human Reproduction
https://www.readbyqxmd.com/read/30550953/targeting-stats-in-neuroinflammation-the-road-less-traveled
#2
REVIEW
Seyed Mohammad Nabavi, Touqeer Ahmed, Maheen Nawaz, Kasi Pandima Devi, Devasahayam Jaya Balan, Valeria Pittalà, Sandro Argüelles-Castilla, Lara Testai, Haroon Khan, Antoni Sureda, Marcos Roberto de Oliveira, Rosa Anna Vacca, Suowen Xu, Bahman Yousefi, Valeria Curti, Maria Daglia, Eduardo Sobarzo-Sánchez, Rosanna Filosa, Seyed Fazel Nabavi, Maryam Majidinia, Ahmad Reza Dehpour, Samira Shirooie
JAK/STAT transduction pathway is a highly conserved pathway implicated in regulating cellular proliferation, differentiation, survival and apoptosis. Dysregulation of this pathway is involved in the onset of autoimmune, haematological, oncological, metabolic and neurological diseases. Over the last few years, the research of anti-neuroinflammatory agents has gained considerable attention. The ability to diminish the STAT-induced transcription of inflammatory genes is documented for both natural compounds (such as polyphenols) and chemical drugs...
December 11, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30550940/carrier-free-nanoparticles-of-cathepsin-b-cleavable-peptide-conjugated-doxorubicin-prodrug-for-cancer-targeting-therapy
#3
Man Kyu Shim, Jooho Park, Hong Yeol Yoon, Sangmin Lee, Wooram Um, Jong-Ho Kim, Sun-Woong Kang, Joung-Wook Seo, Soo-Wang Hyun, Jae Hyung Park, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim
Cancer nanomedicine using nanoparticle-based delivery systems has shown outstanding promise in recent decades for improving anticancer treatment. However, limited targeting efficiency, low drug loading efficiency and innate toxicity of nanoparticles have caused severe problems, leaving only a few available in the clinic. Here, we newly developed carrier-free nanoparticles of cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly; FRRG)-conjugated doxorubicin (DOX) prodrug (FRRG-DOX) that formed a stable nanoparticle structure with an average diameter of 213 nm in aqueous condition...
December 11, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30550096/-modern-ethiotropic-chemotherapy-of-human-cytomegalovirus-infection-clinical-effectiveness-molecular-mechanism-of-action-drug-resistance-new-trends-and-prospects-part-1
#4
REVIEW
V L Andronova
Modern chemotherapy of cytomegalovirus (CMV) infections has a very limited arsenal of first-line drugs. These are preparations of ganciclovir (GCV) belonging to the class of modified nucleosides and its metabolic precursor ganciclovir valine ester. After three-step phosphorylation, GCV, as a structural analogue of the natural nucleotide, competes with it for binding to DNA polymerase and, due to its structural features, inhibits its activity. However, with prolonged use of GCV, mainly under conditions of immunosuppression, the virus develops drug resistance associated in most cases with changes in pUL97 catalyzing the first stage of GCV phosphorylation, as well as in the catalytic subunit of DNA polymerase...
2018: Voprosy Virusologii
https://www.readbyqxmd.com/read/30549448/poly-%C3%AE-amino-esters-synthesis-formulations-and-their-biomedical-applications
#5
REVIEW
Yong Liu, Yuanfeng Li, Damla Keskin, Linqi Shi
Poly(β-amino ester) (abbreviated as PBAE or PAE) refers to a polymer synthesized from an acrylate and an amine by Michael addition and has properties inherent to tertiary amines and esters, such as pH responsiveness and biodegradability. The versatility of building blocks provides a library of polymers with miscellaneous physicochemical and mechanical properties. When used alone or together with other materials, PBAEs can be fabricated into different formulations in order to fulfill various requirements in drug delivery (for instance, gene, anticancer drugs, and antimicrobials delivery) and natural complex mimicry (nanochaperones)...
December 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/30549424/extracellular-vesicle-mimetic-ghost-nanovesicles-for-delivering-anti-inflammatory-drugs-to-mitigate-gram-negative-bacterial-outer-membrane-vesicle-induced-systemic-inflammatory-response-syndrome
#6
Gyeongyun Go, Jaewook Lee, Dong-Sic Choi, Sang Soo Kim, Yong Song Gho
Sepsis is one of the major causes of death in hospital patients and is represented by systemic inflammatory response syndrome (SIRS) associated with infection. Gram-negative bacteria including Escherichia coli can provoke sepsis by stimulating the immune systems. Outer membrane vesicles (OMVs), nanosized vesicular structures derived from Gram-negative bacteria, contain several pathogen-associated molecular patterns, and are demonstrated to mediate SIRS. Here, extracellular vesicle-mimetic ghost nanovesicles loaded with dexamethasone, an anti-inflammatory drug, are developed using alkaline solution, sonication, and buoyant density gradient ultracentrifugation...
December 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/30549180/chalcone-flavokawain-a-attenuates-tgf-%C3%AE-1-induced-fibrotic-pathology-via-inhibition-of-ros-smad3-signaling-pathways-and-induction-of-nrf2-are-mediated-antioxidant-genes-in-vascular-smooth-muscle-cells
#7
You-Cheng Hseu, Ting-Yu Yang, Mei-Ling Li, Peramaiyan Rajendran, Dony Chacko Mathew, Chia-Hsuan Tsai, Ruei-Wan Lin, Chuan-Chen Lee, Hsin-Ling Yang
TGF-β1 plays a crucial role in the pathogenesis of vascular fibrotic diseases. Chalcones are reportedly cancer chemo-preventive food components that are rich in fruits and vegetables. In this study, flavokawain A (FKA, 2-30 μM), a naturally occurring chalcone in kava extracts, was evaluated for its anti-fibrotic and antioxidant properties in TGF-β1-stimulated vascular smooth muscle (A7r5) cells, as well as its underlying molecular mechanism of action. Immunofluorescence data showed down-regulated F-actin expression with FKA treatment in TGF-β1-stimulated A7r5 cells...
December 13, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/30548592/long-term-safety-and-drug-survival-of-acitretin-in-psoriasis-a-retrospective-observational-study
#8
Leena Chularojanamontri, Narumol Silpa-Archa, Chanisada Wongpraparut, Pichaya Limphoka
BACKGROUND: This retrospective observational study aimed to investigate the long-term safety, drug survival, and factors associated with the survival of acitretin in a real-world setting. METHODS: Data of adult patients with psoriasis who attended Siriraj Hospital between 2012 and 2017 and were treated with acitretin were reviewed. Demographic data and clinical courses were recorded. The Kaplan-Meier curve and Cox regression were used to calculate drug survival and the factors associated with drug survival, respectively...
December 13, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/30548573/identification-of-new-urinary-gamma-hydroxybutyric-acid-ghb-markers-applying-untargeted-metabolomics-analysis-following-placebo-controlled-administration-to-humans
#9
Andrea E Steuer, Justine Raeber, Christian Steuer, Martina I Boxler, Dario A Dornbierer, Oliver G Bosch, Boris B Quednow, Erich Seifritz, Thomas Kraemer
Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid that occurs naturally in the mammalian brain and that is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock-out drug in cases of drug facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 h in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use...
December 12, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/30548473/the-insights-into-molecular-pathways-of-hypoxia-inducible-factor-in-the-brain
#10
REVIEW
Robert P Ostrowski, John H Zhang
The objectives of this present work were to review recent developments on the role of hypoxia-inducible factor (HIF) in the survival of cells under normoxic versus hypoxic and inflammatory brain conditions. The dual nature of HIF effects appears well established, based on the accumulated evidence of HIF playing both the role of adaptive factor and mediator of cell demise. Cellular HIF responses depend on pathophysiological conditions, developmental phase, comorbidities, and administered medications. In addition, HIF-1α and HIF-2α actions may vary in the same tissues...
December 12, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/30548188/covalent-vs-non-covalent-inhibition-tackling-drug-resistance-in-egfr-a-thorough-dynamic-perspective
#11
Farideh Badichi Akher, Abdolkarim Farrokhzadeh, Mahmoud Soliman
A persistent challenge in the treatment of non-small cell lung cancer (NSCLC) with EGFR is the emergence of drug-resistant caused by somatic mutations. The EGFR L858R/T790M double mutant (EGFRDM) was found to be the most alarming variant. Despite the development of a wide range of inhibitors, none of them could inhibit EGFRDM effectively. Recently, 11h and 45a, have been found to be potent inhibitors against EGFRDM through two distinctive mechanisms, non-covalent and covalent binding, respectively. However, the structural and dynamic implications of the two modes of inhibitions remain unexplored...
December 11, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/30547450/heter-lp-a-heterogeneous-label-propagation-method-for-drug-repositioning
#12
Maryam Lotfi Shahreza, Nasser Ghadiri, James R Green
Using existing drugs for diseases which are not developed for their treating (drug repositioning) provides a new approach to developing drugs at a lower cost, faster, and more secured. We proposed a method for drug repositioning which can predict simple and complex relationships between drugs, drug targets, and diseases. Since biological networks typically present a suitable model for relationships between different biological concepts, our primary approach is to analyze graphs and complex networks in the study of drugs and their therapeutic effects...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30547444/integrating-biological-networks-for-drug-target-prediction-and-prioritization
#13
Xiao Ji, Johannes M Freudenberg, Pankaj Agarwal
Computational prediction of the clinical success or failure of a potential drug target for therapeutic use is a challenging problem. Novel network propagation algorithms that integrate heterogeneous biological networks are proving useful for drug target identification and prioritization. These approaches typically utilize a network describing relationships between targets, a method to disseminate the relevant information through the network, and a method to elucidate new associations between targets and diseases...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30546958/immunoprofiles-of-colorectal-cancer-from-lynch-syndrome
#14
Joanna Walkowska, Thomas Kallemose, Göran Jönsson, Mats Jönsson, Ove Andersen, Mads Hald Andersen, Inge Marie Svane, Anne Langkilde, Mef Nilbert, Christina Therkildsen
Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome versus hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors...
2019: Oncoimmunology
https://www.readbyqxmd.com/read/30546895/beneficial-effect-of-additional-treatment-with-widely-available-anticancer-agents-in-advanced-small-lung-cell-carcinoma-a-case-report
#15
Piotr J Kruk
Small-cell lung carcinoma is a type of lung cancer characterized by very poor prognosis, as the majority of the patients have already developed metastases at initial diagnosis. Small-cell lung cancer accounts for ~15% of all lung cancer cases. The present study reports the case of a female patient with advanced-stage small-cell lung cancer. The patient received the standard treatments (6 cycles of platinum and etoposide chemotherapy followed by Gamma Knife treatment of suspicious mediastinal lymphnodes); in addition, naturally derived agents (curcumin, parthenolide, betuline, sulforaphane, withanolides, lactoferrin, pomegranate fruit extract, flaxseed and dioscorea) were alternately administered at increased doses, while previously prescribed medications for other comorbidities (metformin and atorvastatin) were continued...
December 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/30546858/does-size-really-matter-probing-the-efficacy-of-structural-reduction-in-the-optimization-of-bioderived-compounds-a-computational-proof-of-concept
#16
Fisayo A Olotu, Geraldene Munsamy, Mahmoud E S Soliman
Over the years, numerous synthetic approaches have been utilized in drug design to improve the pharmacological properties of naturally derived compounds and most importantly, minimize toxic effects associated with their transition to drugs. The reduction of complex bioderived compounds to simpler bioactive fragments has been identified as a viable strategy to develop lead compounds with improved activities and minimal toxicities. Although this 'reductive' strategy has been widely exemplified, underlying biological events remain unresolved, hence the unanswered question remains how does the fragmentation of a natural compound improve its bioactivity and reduce toxicities? Herein, using a combinatorial approach, we initialize a computational "proof-of- concept" to expound the differential pharmacological and antagonistic activities of a natural compound, Anguinomycin D, and its synthetic fragment, SB640 towards Exportin Chromosome Region Maintenance 1 (CRM1)...
2018: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/30546259/training-augmented-intelligent-capabilities-for-pharmacovigilance-applying-deep-learning-approaches-to-individual-case-safety-report-processing
#17
Danielle Abatemarco, Sujan Perera, Sheng Hua Bao, Sameen Desai, Bruno Assuncao, Niki Tetarenko, Karolina Danysz, Ruta Mockute, Mark Widdowson, Nicole Fornarotto, Sheryl Beauchamp, Salvatore Cicirello, Edward Mingle
Introduction: Regulations are increasing the scope of activities that fall under the remit of drug safety. Currently, individual case safety report (ICSR) collection and collation is done manually, requiring pharmacovigilance professionals to perform many transactional activities before data are available for assessment and aggregated analyses. For a biopharmaceutical company to meet its responsibilities to patients and regulatory bodies regarding the safe use and distribution of its products, improved business processes must be implemented to drive the industry forward in the best interest of patients globally...
2018: Pharmaceutical Medicine
https://www.readbyqxmd.com/read/30546230/chemoprotective-effect-of-nanocurcumin-on-5-fluorouracil-induced-toxicity-toward-oral-cancer-treatment
#18
Saurabh Srivastava, Shadab Mohammad, Shalini Gupta, Abbas Ali Mahdi, Rakesh Kumar Dixit, Vibha Singh, Fahad Mansoor Samadi
Introduction: Cancer of oral cavity is the uncontrolled expansion of damaged cell within the mouth cavity. 5-fluorouracil (5-FU) chemotherapy was focused to kill the cancer cell, but it would affect the surrounding normal cells during oral cancer treatment. This study included the evaluation of chemoprotective effects of curcumin (CU), as an herbal remedy, on 5-FU-induced-cytotoxicity toward oral cancer treatment, loaded within a nanocarrier system. CU was combined with 5-FU chemotherapy as a combinational drug-delivery system to evaluate synergistic effects...
July 2018: National Journal of Maxillofacial Surgery
https://www.readbyqxmd.com/read/30545944/the-immunosuppressant-macrolide-tacrolimus-activates-cold-sensing-trpm8-channels
#19
José Miguel Arcas, Alejandro González, Katharina Gers-Barlag, Omar González-González, Federico Bech, Lusine Demirkhanyan, Eleonora Zakharian, Carlos Belmonte, Ana Gomis, Félix Viana
TRPM8 is a polymodal, non-selective cation channel activated by cold temperature and cooling agents that plays a critical role in the detection of environmental cold. We found that TRPM8 is a pharmacological target of tacrolimus (FK506), a macrolide immunosuppressant with several clinical uses, including the treatment of organ rejection following transplants, treatment of atopic dermatitis and dry eye disease. Tacrolimus is an inhibitor of the phosphatase calcineurin, an action shared with cyclosporine.Tacrolimus activates TRPM8 channels in different species, including humans, and sensitizes their response to cold temperature by inducing a leftward shift in the voltage-dependent activation curve...
December 13, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/30545684/ephrin-type-b-receptor-4-affinity-chromatography-an-effective-and-rapid-method-studying-the-active-compounds-targeting-ephrin-type-b-receptor-4
#20
Man Zhu, Yuxin Cui, Liu Yang, Tianfeng Yang, Hongying Wang, Dongdong Zhang, Weina Ma, Yanmin Zhang
Erythropoietin-producing hepatocyte B4 (EphB4) has recently been reported to be an oncogenic factor in many cancers and overexpressed in several types of tumors. Thus, EphB4 has the potential to be a therapeutic target in these malignancies. High-performance affinity chromatography has been a powerful tool to study the interaction between drugs and receptors. In this study, we constructed a novel EphB4 affinity chromatography model to investigate the active compounds which can target EphB4. More than 50 crude extracts of traditional Chinese medicine were screened by this affinity chromatography model...
December 4, 2018: Journal of Chromatography. A
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