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Innovative Drugs

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https://www.readbyqxmd.com/read/30540959/screening-based-chemical-approaches-to-unravel-stem-cell-biology
#1
REVIEW
Shuibing Chen
Cell-permeable compounds provide a convenient and efficient approach to manipulate biological processes. A number of compounds controlling stem cell self-renewal, survival, differentiation, and reprogramming have been identified through high-throughput/content screens. Using these powerful chemical tools, strategies have been developed to direct human pluripotent stem cell (hPSC) differentiation to functional cells. Recently, hPSC-derived cells and organoids are used to model human diseases, which can be adapted to a high-throughput/content platform for chemical screens...
December 11, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/30539697/generation-of-a-primary-hyperoxaluria-type-1-disease-model-via-crispr-cas9-system-in-rats
#2
Rui Zheng, Xiaoliang Fang, Lei He, Yanjiao Shao, Nana Guo, Liren Wang, Mingyao Liu, Dali Li, Hongquan Geng
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an inherited disease caused by mutations in alanine-glyoxylate aminotransferase (AGXT). It is characterized by abnormal metabolism of glyoxylic acid in liver leading to endogenous oxalate overproduction and deposition of oxalate in multiple organs, mainly the kidney. Patients of PH1 often suffer from recurrent urinary tract stones, and finally renal failure. There is no effective treatment other than combined liver-kidney transplantation...
December 11, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30538786/biobanks-in-horizon-2020-sustainability-and-attractive-perspectives
#3
REVIEW
Judita Kinkorová, Ondřej Topolčan
Biobanks have during last two decades gained an important role in the whole process of biomedical research and health care not only in Europe but also worldwide. Biobanks are one of the pillars in personalised medicine tackling all its aspects such as prevention, diagnosis, treatment and monitoring closely the specific characteristics of an individual patient. The current and future power of biobanks is the amount of samples of high-quality and related information available for current and future research of diseases, for optimising patients´ prevention, diagnosis, treatment and monitoring...
December 2018: EPMA Journal
https://www.readbyqxmd.com/read/30537658/piezoelectric-barium-titanate-nanostimulators-for-the-treatment-of-glioblastoma-multiforme
#4
Attilio Marino, Enrico Almici, Simone Migliorin, Christos Tapeinos, Matteo Battaglini, Valentina Cappello, Marco Marchetti, Giuseppe de Vito, Riccardo Cicchi, Francesco Saverio Pavone, Gianni Ciofani
Major obstacles to the successful treatment of gliolastoma multiforme are mostly related to the acquired resistance to chemotherapy drugs and, after surgery, to the cancer recurrence in correspondence of residual microscopic foci. As innovative anticancer approach, low-intensity electric stimulation represents a physical treatment able to reduce multidrug resistance of cancer and to induce remarkable anti-proliferative effects by interfering with Ca2+ and K+ homeostasis and by affecting the organization of the mitotic spindles...
December 4, 2018: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/30536603/ethics-codes-and-use-of-new-and-innovative-drugs
#5
REVIEW
Jan Borysowski, Hans-Jörg Ehni, Andrzej Górski
Treatment with new and/or innovative drugs with uncertain safety and efficacy profile is associated with substantial ethical concerns. The main objective of this paper is to present guidance on the use of such drugs contained in: 1) major international codes and guidelines pertaining to medical ethics and biomedical research; 2) national codes of medical ethics and professional conduct of the US, Canada, Australia, New Zealand, the UK, Ireland, France and Germany. Out of the four international codes and guidelines analyzed, only the Declaration of Helsinki addresses the question of the use of unproven drugs...
December 9, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/30536577/synthesis-and-biological-evaluation-of-substituted-indole-and-its-analogs-as-influenza-a-virus-inhibitors
#6
Xuandi Zhang, Guo-Ning Zhang, Yujia Wang, Mei Zhu, Juxian Wang, Ziqiang Li, Donghui Li, Shan Cen, Yucheng Wang
Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work...
December 9, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/30536071/using-tree-shrews-tupaia-belangeri-as-a-novel-animal-model-of-liver-transplantation
#7
Bo Tang, Tao Wu, Shu-Feng Xiao, Jia-Yun Ge, Dong Wei, Chun-Man Li, Qiu-Hong Wang, Wang Zeng, Bi-Mang Fu, Jie Zhang
Liver transplantation (LT) is most effective and promising approach for end-stage liver disease. However, there remains room for further improvement and innovation, for example, to reduce ischemic reperfusion injury, transplant rejection and immune tolerance. A good animal model of LT is essential for such innovation in transplant research. Although rat LT model has been used since the last century, it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other...
December 2018: Current medical science
https://www.readbyqxmd.com/read/30535941/nop-ligands-for-the-treatment-of-anxiety-and-mood-disorders
#8
Elaine C Gavioli, Victor A D Holanda, Chiara Ruzza
Many studies point toward the nociceptin/orphanin FQ (N/OFQ) and the N/OFQ peptide receptor (NOP) as targets for the development of innovative drugs for treating anxiety- and mood-related disorders. Evidence supports the view that the activation of NOP receptors with agonists elicits anxiolytic-like effects, while its blockade with NOP antagonists promotes antidepressant-like actions in rodents. Genetic studies showed that NOP receptor knockout mice display an antidepressant-like phenotype, and NOP antagonists are inactive in these animals...
December 8, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30535004/direct-activation-of-g-protein-gated-inward-rectifying-k-channels-girk-promotes-non-rapid-eye-movement-sleep
#9
Bende Zou, William S Cao, Zhiwei Guan, Kui Xiao, Conrado Pascual, Julian Xie, Jingxi Zhang, James Xie, Frank Kayser, Craig W Lindsley, C David Weaver, Jidong Fang, Xinmin Simon Xie
Study Objectives: A major challenge in treating insomnia is to find effective medicines with fewer side effects. Activation of G-protein-gated inward rectifying K+ channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) promotes non-rapid eye movement (NREM) sleep and consolidates sleep. However, baclofen has poor brain penetration, GHB possesses abuse liability, and in rodents both drugs cause spike-wave discharges (SWDs), an absence seizure activity. We tested the hypothesis that direct GIRK activation promotes sleep without inducing SWD using ML297, a potent and selective GIRK activator...
December 11, 2018: Sleep
https://www.readbyqxmd.com/read/30534379/pharmacological-profile-of-the-neuropeptide-s-receptor-dynamic-mass-redistribution-studies
#10
Chiara Ruzza, Federica Ferrari, Remo Guerrini, Erika Marzola, Delia Preti, Rainer K Reinscheid, Girolamo Calo
Neuropeptide S (NPS) is the endogenous ligand of the neuropeptide S receptor (NPSR). NPS modulates several biological functions including anxiety, wakefulness, pain, and drug abuse. The aim of this study was the investigation of the pharmacological profile of NPSR using the dynamic mass redistribution (DMR) assay. DMR is a label-free assay that offers a holistic view of cellular responses after receptor activation. HEK293 cells stably transfected with the murine NPSR (HEK293mNPSR ) have been used. To investigate the nature of the NPS-evoked DMR signaling, FR900359 (Gq inhibitor), pertussis toxin (Gi inhibitor), and rolipram (phosphodiesterase inhibitor) were used...
December 2018: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/30534121/artificial-activation-of-escherichia-coli-mazef-and-hipba-toxin-antitoxin-systems-by-antisense-peptide-nucleic-acids-as-an-antibacterial-strategy
#11
Marcin Równicki, Tomasz Pieńko, Jakub Czarnecki, Monika Kolanowska, Dariusz Bartosik, Joanna Trylska
The search for new, non-standard targets is currently a high priority in the design of new antibacterial compounds. Bacterial toxin-antitoxin systems (TAs) are genetic modules that encode a toxin protein that causes growth arrest by interfering with essential cellular processes, and a cognate antitoxin, which neutralizes the toxin activity. TAs have no human analogs, are highly abundant in bacterial genomes, and therefore represent attractive alternative targets for antimicrobial drugs. This study demonstrates how artificial activation of Escherichia coli mazEF and hipBA toxin-antitoxin systems using sequence-specific antisense peptide nucleic acid oligomers is an innovative antibacterial strategy...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30532973/chemical-interventions-for-the-opioid-crisis-key-advances-and-remaining-challenges
#12
Margaret E Olson, Lisa M Eubanks, Kim D Janda
The present United States opioid crisis requires urgent and innovative scientific intervention. This perspective highlights a role for the chemical sciences by expounding upon three key research areas identified as priorities by the National Institute on Drug Abuse (NIDA). Specifically, important advances in chemical interventions for overdose reversal, strategies for opioid use disorder (OUD) treatment, including immunopharmacotherapies, and next-generation alternatives for pain management will be discussed...
December 11, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/30531068/an-innovative-approach-for-the-treatment-of-alzheimer-s-disease-the-role-of-peroxisome-proliferator-activated-receptors-and-their-ligands-in-development-of-alternative-therapeutic-interventions
#13
REVIEW
Luca Piemontese
Alzheimer's disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment. This innovative approach will lead to the identification of new targets for the preparation of new effective drugs. Peroxisome proliferator-activated receptors and their ligands are the ideal candidates to reach the necessary breakthrough to defeat this complicate disease.
January 2019: Neural Regeneration Research
https://www.readbyqxmd.com/read/30529726/inpentasomes-an-innovative-nose-to-brain-pentamidine-delivery-blunts-mptp-parkinsonism-in-mice
#14
F Rinaldi, L Seguella, S Gigli, P N Hanieh, E Del Favero, L Cantù, M Pesce, G Sarnelli, C Marianecci, G Esposito, M Carafa
Preclinical and clinical evidences have demonstrated that astroglial-derived S100B protein is a key element in neuroinflammation underlying the pathogenesis of Parkinson's disease (PD), so much as that S100B inhibitors have been proposed as promising candidates for PD targeted therapy. Pentamidine, an old-developed antiprotozoal drug, currently used for pneumocystis carinii is one of the most potent inhibitors of S100B activity, but despite this effect, is limited by its low capability to cross blood brain barrier (BBB)...
December 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30529586/a-bright-future-optogenetics-to-dissect-the-spatiotemporal-control-of-cell-behavior
#15
REVIEW
Alexander G Goglia, Jared E Toettcher
Cells sense, process, and respond to extracellular information using signaling networks: collections of proteins that act as precise biochemical sensors. These protein networks are characterized by both complex temporal organization, such as pulses of signaling activity, and by complex spatial organization, where proteins assemble structures at particular locations and times within the cell. Yet despite their ubiquity, studying these spatial and temporal properties has remained challenging because they emerge from the entire protein network rather than a single node, and cannot be easily tuned by drugs or mutations...
December 4, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/30529561/a-dual-fluorescent-reverse-targeting-drug-delivery-system-based-on-curcumin-loaded-ovalbumin-nanoparticles-for-allergy-treatment
#16
Jie Liang, Xia Dong, Afeng Yang, Dunwan Zhu, Deling Kong, Feng Lv
A reverse targeting drug delivery based on antigen-modified nanoparticles provided an innovative strategy for effectively alleviating or inhibiting immune response. In this study, a dual fluorescent reverse targeting drug delivery system based on curcumin-loaded ovalbumin nanoparticles is developed for allergy treatment. The self-crosslinked ovalbumin nanoparticles achieved the double function of reverse targeting and sustained delivery carriers to maximize the anti-allergy of curcumin. Using a murine model of ovalbumin-induced allergy, this drug delivery system suppressed antigen-specific IgG1 and IgE production, inhibited CD4+ T activity, and decreased the level of ovalbumin-sensitized memory B cells...
December 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/30528728/prediction-of-drug-target-interaction-by-integrating-diverse-heterogeneous-information-source-with-multiple-kernel-learning-and-clustering-methods
#17
Xiao-Ying Yan, Shao-Wu Zhang, Chang-Run He
BACKGROUND: Identification of potential drug-target interaction pairs is very important for pharmaceutical innovation and drug discovery. Numerous machine learning-based and network-based algorithms have been developed for predicting drug-target interactions. However, large-scale pharmacological, genomic and chemical datum emerged recently provide new opportunity for further heightening the accuracy of drug-target interactions prediction. RESULTS: In this work, based on the assumption that similar drugs tend to interact with similar proteins and vice versa, we developed a novel computational method (namely MKLC-BiRW) to predict new drug-target interactions...
December 2, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/30528678/new-concepts-to-reduce-glucocorticoid-toxicity
#18
Rieke Alten, Max Mischkewitz
70 years after their first use, low-dose glucocorticoids are a common part of pharmacological rheumatoid arthritis treatment. This is due to their well-proven capacities in symptom severity and disease activity reduction, in particular when combined with a disease-modifying anti-rheumatic drug, such as methotrexate. Nevertheless, glucocorticoid administration, in long-term especially, is also seen critically because of its potential adverse conditions. In order to achieve a reduction in treatment-related adverse events, modern therapy regimes should take into consideration patients' risk factors and therefore be individual...
December 5, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/30528388/the-practical-self-targeted-oncolytic-adenoviral-nanosphere-based-on-immuno-obstruction-method-via-polyprotein-surface-precipitation-technique-enhances-transfection-efficiency-for-virotherapy
#19
Hao Ran, Guilan Quan, Ying Huang, Chune Zhu, Chao Lu, Weibin Liu, Xin Pan, Chuanbin Wu
Recent developments in tumour treatment had focused on virotherapies that were currently revolutionising new innovated treatment pathways. This study focused on the fabrication of oncolytic adenoviral vector (Ad) nanosphere that self-targeted at lung tumour cells (A549), utilising the immune response for upper respiratory tract infection, caused by the Ad infection. This system was dependent upon T-cell immune response, surface charge and blood metabolism. Oncolytic Ad attacked lung A549 tumour cells by incorporated its own DNA to replace A549's, the triggered immune response generated T-cells also further attack A549...
December 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30526582/fortification-of-carica-papaya-fruit-seeds-to-school-meal-snacks-may-aid-africa-mass-deworming-programs-a-preliminary-survey
#20
M Kugo, L Keter, A Maiyo, J Kinyua, P Ndemwa, G Maina, P Otieno, E M Songok
BACKGROUND: Soil transmitted helminths (STHs) are among the world's neglected tropical diseases. Morbidity due to STHs is greatest in school-age children who typically have the highest burden of infection. In 2001, WHO passed a resolution for the use of large-scale mass drug administration (MDA) to deworm vulnerable children through school based programs. Though effective, there is concern that MDA might not be sustainable over extended periods. Additionally the current MDA strategy does not consider child malnutrition, a very common malady in resource limited countries...
December 7, 2018: BMC Complementary and Alternative Medicine
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