14,317 results match your criteria employing pharmacological


Vemurafenib drives EMT gene expression in BRAFi-resistant BRAF/NRAS melanoma enhancing tumor growth and metastasis in a bioluminescent murine model.

J Invest Dermatol 2021 Oct 20. Epub 2021 Oct 20.

University of Arizona, Department of Pharmacology and Toxicology, College of Pharmacy and UA Cancer Center, 1515 N. Campbell Ave., Tucson, AZ 85724, USA. Electronic address:

BRAF-inhibitor (BRAFi)-resistance compromises long term survivorship of malignant melanoma patients, and mutant NRAS is a major mediator of BRAFi-resistance. Here, employing phenotypic and transcriptomic analysis of isogenic melanoma cells that differ only by NRAS mutational status (BRAFi-sensitive A375-BRAF/NRAS versus BRAFi-resistant A375-BRAF/NRAS) we demonstrate that BRAFi (vemurafenib) treatment selectively targets BRAF/NRAS cells upregulating epithelial-to-mesenchymal transition (EMT) gene expression, paradoxically promoting invasiveness and metastasis in vitro and in vivo. First, NanoString nCounter transcriptomic analysis identified upregulation of specific gene expression networks ('EMT' and 'EMT to Metastasis') as a function of NRAS-status. Read More

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October 2021

Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction.

Cells 2021 Sep 25;10(10). Epub 2021 Sep 25.

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates.

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Read More

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September 2021

Improving Curcumin Bioavailability: Current Strategies and Future Perspectives.

Pharmaceutics 2021 Oct 17;13(10). Epub 2021 Oct 17.

Department of Pharmacy, University of Pisa, Via Bonanno 6, I-56126 Pisa, Italy.

Curcumin possesses a plethora of interesting pharmacological effects. Unfortunately, it is also characterized by problematic drug delivery and scarce bioavailability, representing the main problem related to the use of this compound. Poor absorption, fast metabolism, and rapid systemic clearance are the most important factors contributing to low curcumin levels in plasma and tissues. Read More

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October 2021

Molecular and genomic characterisation of a panel of human anal cancer cell lines.

Cell Death Dis 2021 Oct 18;12(11):959. Epub 2021 Oct 18.

Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.

Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. Read More

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October 2021

The Emerging Role of Nanomedicine in the Management of Nonalcoholic Fatty Liver Disease: A State-of-the-Art Review.

Bioinorg Chem Appl 2021 8;2021:4041415. Epub 2021 Oct 8.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that can lead to end-stage liver disease needing a liver transplant. Many pharmacological approaches are used to reduce the disease progression in NAFLD. However, current strategies remain ineffective to reverse the progression of NAFLD completely. Read More

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October 2021

Conformational dynamics of myoglobin in the presence of vitamin B12: A spectroscopic and in silico investigation.

Int J Biol Macromol 2021 Oct 13;192:564-573. Epub 2021 Oct 13.

Department of Physics, Indian Institute of Technology (Indian School of Mines), Dhanbad 826004, Jharkhand, India. Electronic address:

Myoglobin is an essential transport protein of heart and muscle tissues that acts as a local oxygen reservoir and a marker in different diseased conditions. On the other hand, Vitamin B12 is a vital nutrient that helps synthesize red blood cells, DNA, and proteins. To understand the ability of vitamin B12 to bind to the excess of myoglobin produced in the body under certain conditions (muscle injuries, severe trauma, etc. Read More

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October 2021

Nickel-Mediated Alkoxycarbonylation for Complete Carbon Isotope Replacement.

J Am Chem Soc 2021 Oct 13. Epub 2021 Oct 13.

Carbon Dioxide Activation Center (CADIAC), The Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.

Many commercial drugs, as well as upcoming pharmaceutically active compounds in the pipeline, display aliphatic carboxylic acids or derivatives thereof as key structural entities. Synthetic methods for rapidly accessing isotopologues of such compounds are highly relevant for undertaking critical pharmacological studies. In this paper, we disclose a direct synthetic route allowing for full carbon isotope replacement via a nickel-mediated alkoxycarbonylation. Read More

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October 2021

The Neuroprotective Role of Polydatin: Neuropharmacological Mechanisms, Molecular Targets, Therapeutic Potentials, and Clinical Perspective.

Molecules 2021 Oct 2;26(19). Epub 2021 Oct 2.

Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.

Neurodegenerative diseases (NDDs) are one of the leading causes of death and disability in humans. From a mechanistic perspective, the complexity of pathophysiological mechanisms contributes to NDDs. Therefore, there is an urgency to provide novel multi-target agents towards the simultaneous modulation of dysregulated pathways against NDDs. Read More

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October 2021

HDL and reverse cholesterol transport in humans and animals: Lessons from pre-clinical models and clinical studies.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Oct 9;1867(1):159065. Epub 2021 Oct 9.

Division of Translational Medicine & Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104, USA.

The ability to accept cholesterol from cells and to promote reverse cholesterol transport (RCT) represents the best characterized antiatherogenic function of HDL. Studies carried out in animal models have unraveled the multiple mechanisms by which these lipoproteins drive cholesterol efflux from macrophages and cholesterol uptake to the liver. Moreover, the influence of HDL composition and the role of lipid transporters have been clarified by using suitable transgenic models or through experimental design employing pharmacological or nutritional interventions. Read More

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October 2021

Population pharmacokinetics and target attainment analysis of linezolid in multidrug-resistant tuberculosis patients.

Br J Clin Pharmacol 2021 Oct 7. Epub 2021 Oct 7.

Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.

Aim: This study investigates the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of linezolid in patients infected with multidrug-resistant (MDR) tuberculosis (TB).

Methods: A pharmacometric model was developed including 244 timed linezolid concentration samples from 39 patients employing NONMEM® 7.4. Read More

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October 2021

β-Amyloid disruption of LTP/LTD balance is mediated by AKAP150-anchored PKA and Calcineurin regulation of Ca-permeable AMPA receptors.

Cell Rep 2021 Oct;37(1):109786

Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Alzheimer's and Cognition Center, Anschutz Medical Campus, Aurora, CO 80045, USA; Linda Crnic Institute for Down Syndrome, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address:

Regulated insertion and removal of postsynaptic AMPA glutamate receptors (AMPARs) mediates hippocampal long-term potentiation (LTP) and long-term depression (LTD) synaptic plasticity underlying learning and memory. In Alzheimer's disease β-amyloid (Aβ) oligomers may impair learning and memory by altering AMPAR trafficking and LTP/LTD balance. Importantly, Ca-permeable AMPARs (CP-AMPARs) assembled from GluA1 subunits are excluded from hippocampal synapses basally but can be recruited rapidly during LTP and LTD to modify synaptic strength and signaling. Read More

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October 2021

Development of potent remdesivir derivative against SARS-CoV-2 protease inhibitors: Design, modification, molecular modeling and MD simulations.

Pak J Pharm Sci 2021 May;34(3(Supplementary)):1119-1126

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Dow College of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan.

The pandemic Coronavirus (Covid-19) is continuously growing and spreading at the highest rate in all over the world. So, it is necessary to produce the new medicinal agents against this virus. The aim of the present study is to design a potent compound against COVID-19. Read More

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Solar simulated ultraviolet radiation inactivates HCoV-NL63 and SARS-CoV-2 coronaviruses at environmentally relevant doses.

J Photochem Photobiol B 2021 Sep 21;224:112319. Epub 2021 Sep 21.

Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ, United States of America. Electronic address:

The germicidal properties of short wavelength ultraviolet C (UVC) light are well established and used to inactivate many viruses and other microbes. However, much less is known about germicidal effects of terrestrial solar UV light, confined exclusively to wavelengths in the UVA and UVB regions. Here, we have explored the sensitivity of the human coronaviruses HCoV-NL63 and SARS-CoV-2 to solar-simulated full spectrum ultraviolet light (sUV) delivered at environmentally relevant doses. Read More

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September 2021

Antimicrobial peptides - Unleashing their therapeutic potential using nanotechnology.

Pharmacol Ther 2021 Sep 28:107990. Epub 2021 Sep 28.

Institute of Pharmacy, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address:

Antimicrobial peptides (AMPs) are potent, mostly cationic, and amphiphilic broad-spectrum host defense antimicrobials that are produced by all organisms ranging from prokaryotes to humans. In addition to their antimicrobial actions, they modulate inflammatory and immune responses and promote wound healing. Although they have clear benefits over traditional antibiotic drugs, their wide therapeutic utilization is compromised by concerns of toxicity, stability, and production costs. Read More

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September 2021

Losartan ointment attenuates imiquimod-induced psoriasis-like inflammation.

Int Immunopharmacol 2021 Sep 25;100:108160. Epub 2021 Sep 25.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Psoriasis is a chronic skin condition associated with interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Recent evidence declares that angiotensin II (Ang II) induces a potent IL-17-related inflammation. Meanwhile, Losartan, an angiotensin one receptor (AT1R) antagonist, attenuates the TH17-related responses. Read More

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September 2021

[Effects and mechanisms of Supplemented Gegen Qinlian Decoction Formula against podocyte pyroptosis and insulin resistance in model rats with diabetic kidney disease].

Zhongguo Zhong Yao Za Zhi 2021 Sep;46(17):4471-4479

Graduate School of Social Sciences, Faculty of Social Sciences, Hitotsubashi University Tokyo 186-8601, Japan.

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). Read More

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September 2021

Sulfonium Ligands of the α7 nAChR.

Molecules 2021 Sep 17;26(18). Epub 2021 Sep 17.

Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610-0267, USA.

The α7 nicotinic acetylcholine receptor (nAChR) is an important target given its role in cognitive function as well as in the cholinergic anti-inflammatory pathway, where ligands that are effective at stabilizing desensitized states of the receptor are of particular interest. The typical structural element associated with a good desensitizer is the ammonium pharmacophore, but recent work has identified that a trivalent sulfur, in the positively charged sulfonium form, can substitute for the nitrogen in the ammonium pharmacophore. However, the breadth and scope of employing the sulfonium group is largely unexplored. Read More

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September 2021

Synthetic Strategies in the Preparation of Phenanthridinones.

Molecules 2021 Sep 13;26(18). Epub 2021 Sep 13.

Organic Chemistry Department, Science Faculty, RUDN University, Miklukho-Maklaya St., 6, 117198 Moscow, Russia.

Phenanthridinones are important heterocyclic frameworks present in a variety of complex natural products, pharmaceuticals and displaying wide range of pharmacological actions. Its structural importance has evoked a great deal of interest in the domains of organic synthesis and medicinal chemistry to develop new synthetic methodologies, as well as novel compounds of pharmaceutical interest. This review focuses on the synthesis of phenanthridinone scaffolds by employing aryl-aryl, -aryl, and biaryl coupling reactions, decarboxylative amidations, and photocatalyzed reactions. Read More

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September 2021

Mitochondrial Dysfunction in Diseases, Longevity, and Treatment Resistance: Tuning Mitochondria Function as a Therapeutic Strategy.

Genes (Basel) 2021 Aug 29;12(9). Epub 2021 Aug 29.

Department of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima-City 890-8544, Kagoshima, Japan.

Mitochondria are very important intracellular organelles because they have various functions. They produce ATP, are involved in cell signaling and cell death, and are a major source of reactive oxygen species (ROS). Mitochondria have their own DNA (mtDNA) and mutation of mtDNA or change the mtDNA copy numbers leads to disease, cancer chemo/radioresistance and aging including longevity. Read More

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Phytochemicals: A Promising Weapon in the Arsenal against Antibiotic-Resistant Bacteria.

Antibiotics (Basel) 2021 Aug 26;10(9). Epub 2021 Aug 26.

Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran.

The extensive usage of antibiotics and the rapid emergence of antimicrobial-resistant microbes (AMR) are becoming important global public health issues. Many solutions to these problems have been proposed, including developing alternative compounds with antimicrobial activities, managing existing antimicrobials, and rapidly detecting AMR pathogens. Among all of them, employing alternative compounds such as phytochemicals alone or in combination with other antibacterial agents appears to be both an effective and safe strategy for battling against these pathogens. Read More

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S100B as a biomarker of blood-brain barrier disruption after thoracoabdominal aortic aneurysm repair: a secondary analysis from a prospective cohort study.

Can J Anaesth 2021 Sep 27. Epub 2021 Sep 27.

Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.

Purpose: The objective of this study was to determine whether the magnitude of the peripheral inflammatory response to cardiovascular surgery is associated with increases in blood-brain barrier (BBB) permeability as reflected by changes in cerebrospinal fluid (CSF)/plasma S100B concentrations.

Methods: We conducted a secondary analysis from a prospective cohort study of 35 patients undergoing elective thoracoabdominal aortic aneurysm repair with (n = 17) or without (n = 18) cardiopulmonary bypass (CPB). Plasma and CSF S100B, interleukin-6 (IL-6), and albumin concentrations were measured at baseline (C) and serially for up to five days. Read More

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September 2021

A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation.

Drug Deliv Transl Res 2021 Sep 24. Epub 2021 Sep 24.

Department of Biomedical Engineering, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA.

Background Extending the lifespan of subcutaneous insulin administration sets and infusion pumps requires overcoming unreliable insulin delivery induced by dermal reactions. All commercially available insulin formulations contain insulin phenolic preservatives (IPP), which stabilize the insulin molecule but result in unwanted cell and tissue toxicity. Mast cells, which are the first line of defense once the epithelium is breached, are particularly abundant beneath the skin surface. Read More

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September 2021

ERα is an RNA-binding protein sustaining tumor cell survival and drug resistance.

Cell 2021 Sep 23;184(20):5215-5229.e17. Epub 2021 Sep 23.

Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:

Estrogen receptor α (ERα) is a hormone receptor and key driver for over 70% of breast cancers that has been studied for decades as a transcription factor. Unexpectedly, we discover that ERα is a potent non-canonical RNA-binding protein. We show that ERα RNA binding function is uncoupled from its activity to bind DNA and critical for breast cancer progression. Read More

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September 2021

Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury.

Front Neurol 2021 7;12:729184. Epub 2021 Sep 7.

Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg, MB, Canada.

Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the "one-treatment fits all" approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. Read More

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September 2021

Dopaminergic co-transmission with sonic hedgehog inhibits abnormal involuntary movements in models of Parkinson's disease and L-Dopa induced dyskinesia.

Commun Biol 2021 09 22;4(1):1071. Epub 2021 Sep 22.

Department of Molecular, Cellular and Biomedical Sciences, CUNY School of Medicine at City College of New York, City University of New York, New York, NY, USA.

L-Dopa induced dyskinesia (LID) is a debilitating side effect of dopamine replacement therapy for Parkinson's Disease. The mechanistic underpinnings of LID remain obscure. Here we report that diminished sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons facilitates the formation and expression of LID. Read More

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September 2021

Employing the Operational Model to Measure System-Independent OTR Efficacy.

Methods Mol Biol 2022 ;2384:201-220

Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.

Ideally, pharmacological analysis is based on quantitative measurements applied toward unveiling biological mechanisms and guiding medicinal chemistry efforts in drug discovery and basic research. The most robust analysis frameworks generate findings which can be dissociated from the specific experimental setting to provide insights of a broader scope. With insufficient efficacy being the leading cause of drug failures in late-stage clinical trials, more rigorous preclinical definitions might assist in better translation. Read More

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January 2022

Roadmap for the use of base editors to decipher drug mechanism of action.

PLoS One 2021 21;16(9):e0257537. Epub 2021 Sep 21.

Simulation and Modelling Sciences, Pfizer, Cambridge, Massachusetts, United States of America.

CRISPR base editors are powerful tools for large-scale mutagenesis studies. This kind of approach can elucidate the mechanism of action of compounds, a key process in drug discovery. Here, we explore the utility of base editors in an early drug discovery context focusing on G-protein coupled receptors. Read More

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September 2021

Disrupted relationship between blood glucose and brain dopamine D2/3 receptor binding in patients with first-episode schizophrenia.

Neuroimage Clin 2021 Sep 13;32:102813. Epub 2021 Sep 13.

Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Austria. Electronic address:

An elemental function of brain dopamine is to coordinate cognitive and motor resources for successful exploitation of environmental energy sources. Dopamine transmission, goal-directed behavior, and glucose homeostasis are altered in schizophrenia patients prior to and after initiation of pharmacological treatment. Thus, we investigated the relationship between blood glucose levels and brain dopamine signaling in drug-naïve patients with first-episode psychosis. Read More

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September 2021

Fast Optical Investigation of Cardiac Electrophysiology by Parallel Detection in Multiwell Plates.

Front Physiol 2021 3;12:692496. Epub 2021 Sep 3.

European Laboratory for Non-linear Spectroscopy, Sesto Fiorentino, Italy.

Current techniques for fast characterization of cardiac electrophysiology employ optical technologies to control and monitor action potential features of single cells or cellular monolayers placed in multiwell plates. High-speed investigation capacities are commonly achieved by serially analyzing well after well employing fully automated fluorescence microscopes. Here, we describe an alternative cost-effective optical approach (MULTIPLE) that exploits high-power LED arrays to globally illuminate a culture plate and an sCMOS sensor for parallel detection of the fluorescence coming from multiple wells. Read More

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September 2021

Towards Pharma 4.0 in clinical trials: A future-orientated perspective.

Drug Discov Today 2021 Sep 16. Epub 2021 Sep 16.

Centre for Pharmaceutical Engineering Science, University of Bradford, Bradford, UK.

Pharma 4.0, a technology ecosystem in drug development analogous to Industry 4.0 in healthcare, is transforming the traditional approach to drug discovery and development, aligning product quality with less time to market, and creating intelligent stakeholder networks through effective collaborations. Read More

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September 2021