journal
https://read.qxmd.com/read/37429736/optical-approaches-for-investigating-neuromodulation-and-g-protein-coupled-receptor-signaling
#21
JOURNAL ARTICLE
David J Marcus, Michael R Bruchas
Despite that fact roughly 40% of all FDA approved pharmacological therapeutics target G Protein-Coupled Receptors (GPCRs), there remains a noted gap in our understanding of the physiological and functional role of these receptors at the systems level. While heterologous expression systems and in vitro assays have revealed a tremendous amount about GPCR signaling cascades, how these cascades interact across cell types, tissues, and organ systems remains obscure. Classic behavioral pharmacology experiments lack both the temporal and spatial resolution to resolve these long-standing issues...
July 10, 2023: Pharmacological Reviews
https://read.qxmd.com/read/36918261/current-and-emerging-pharmacological-targets-and-treatments-of-urinary-incontinence-and-related-disorders
#22
REVIEW
Martin C Michel, Linda Cardozo, Christopher J Chermansky, Francisco Cruz, Yasuhiko Igawa, Kyu-Sung Lee, Arun Sahai, Alan J Wein, Karl-Erik Andersson
Overactive bladder syndrome with and without urinary incontinence and related conditions, signs, and disorders such as detrusor overactivity, neurogenic lower urinary tract dysfunction, underactive bladder, stress urinary incontinence, and nocturia are common in the general population and have a major impact on the quality of life of the affected patients and their partners. Based on the deliberations of the subcommittee on pharmacological treatments of the 7th International Consultation on Incontinence, we present a comprehensive review of established drug targets in the treatment of overactive bladder syndrome and the aforementioned related conditions and the approved drugs used in its treatment...
July 2023: Pharmacological Reviews
https://read.qxmd.com/read/37328294/-effects-of-medications-on-heat-loss-capacity-in-chronic-disease-patients-health-implications-amidst-global-warming
#23
JOURNAL ARTICLE
Jericho Wee, Xiang Ren Tan, Samuel H Gunther, Mohammed Ihsan, Melvin Khee Shing Leow, Doreen Su-Yin Tan, Johan G Eriksson, Jason Kai Wei Lee
Pharmacological agents used to treat or manage diseases can modify the level of heat strain experienced by chronically ill and elderly patients via different mechanistic pathways. Human thermoregulation is a crucial homeostatic process that maintains body temperature within a narrow range during heat stress through dry (i.e., increasing skin blood flow) and evaporative (i.e., sweating) heat loss, as well as active inhibition of thermogenesis, which is crucial to avoid overheating. Medications can independently and synergistically interact with ageing and chronic disease to alter homeostatic responses to rising body temperature during heat stress...
June 16, 2023: Pharmacological Reviews
https://read.qxmd.com/read/37321860/-oxycodone-a-current-perspective-on-its-pharmacology-abuse-and-pharmacotherapeutic-developments
#24
JOURNAL ARTICLE
James E Barrett, Aryan Shekarabi, Saadet Inan
ABSTRACT Oxycodone, a semi-synthetic derivative of naturally occurring thebaine, an opioid alkaloid, has been available for over 100 years. Although thebaine cannot be used therapeutically due to the occurrence of convulsions at higher doses, it has been converted to a number of other widely used compounds that include naloxone, naltrexone, buprenorphine, and oxycodone. Despite the early identification of oxycodone, it was not until the 1990s that clinical studies began to explore its analgesic efficacy. These studies were followed by the pursuit of several preclinical studies to examine the analgesic effects and abuse liability of oxycodone in laboratory animals and the subjective effects in human volunteers...
June 15, 2023: Pharmacological Reviews
https://read.qxmd.com/read/37295951/-lymphocyte-depleting-and-modulating-therapies-for-chronic-lung-allograft-dysfunction
#25
JOURNAL ARTICLE
Saskia Bos, Pauline Pradère, Hanne Beeckmans, Andrea Zajacova, Bart M Vanaudenaerde, Andrew J Fisher, Robin Vos
Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilising the loss of or modestly improving lung function, with disease progression resuming over time in the majority of patients. Therefore, identification of effective treatments that prevent the onset or halt progression of CLAD is urgently needed...
June 9, 2023: Pharmacological Reviews
https://read.qxmd.com/read/37280098/-the-myc-family-and-the-metastasis-suppressor-ndrg1-targeting-key-molecular-interactions-with-innovative-therapeutics
#26
JOURNAL ARTICLE
Zhao Deng, Des R Richardson
Cancer is a leading cause of death worldwide resulting in ~10 million deaths in 2020. Major oncogenic effectors are the Myc proto-oncogene family that consists of three members including c-Myc, N-Myc, and L-Myc. As a pertinent example of the role of the Myc family in tumorigenesis, amplification of MYCN in childhood neuroblastoma strongly correlates with poor patient prognosis. Complexes between Myc oncoproteins and their partners such as hypoxia-inducible factor-1α (HIF-1α) and Myc-associated protein X (MAX) results in proliferation arrest and pro-proliferative effects, respectively...
June 6, 2023: Pharmacological Reviews
https://read.qxmd.com/read/37280097/-extracellular-vesicle-heterogeneity-and-its-impact-for-regenerative-medicine-applications
#27
JOURNAL ARTICLE
Simonides Immanuel van de Wakker, Fleur Michelle Meijers, Joost Petrus Gerardus Sluijter, Pieter Vader
Extracellular vesicles (EVs) are cell-derived membrane enclosed particles that are involved in physiological and pathological processes. EVs are increasingly being studied for therapeutic applications in the field of regenerative medicine. Therapeutic application of stem cell-derived EVs has shown great potential to stimulate tissue repair. However, the exact mechanisms through which they induce this effect has not been fully clarified. This may to a large extent be attributed to a lack of knowledge on EV heterogeneity...
June 6, 2023: Pharmacological Reviews
https://read.qxmd.com/read/37137717/paradoxes-of-cellular-sumoylation-regulation-a-role-of-biomolecular-condensates
#28
JOURNAL ARTICLE
Xiaodong Cheng, Wenli Yang, Wei Lin, Fang Mei
Protein SUMOylation is a major post-translational modification important for maintaining cellular homeostasis. SUMOylation has long been associated with stress responses as a diverse array of cellular stress signals are known to trigger rapid alternations in global protein SUMOylation. In addition, while there are large families of ubiquitination enzymes, all SUMOs are conjugated by a set of enzymatic machinery comprising one heterodimeric SUMO-activating enzyme, a single SUMO-conjugating enzyme, and a small number of SUMO protein ligases and SUMO-specific proteases...
May 3, 2023: Pharmacological Reviews
https://read.qxmd.com/read/37127349/pharmacological-regulation-of-endoplasmic-reticulum-structure-and-calcium-dynamics-importance-for-neurodegenerative-diseases
#29
JOURNAL ARTICLE
Ilmari Parkkinen, Anna Their, Muhammad Yasir Asghar, Sreesha Sree, Eija Jokitalo, Mikko Airavaara
The endoplasmic reticulum (ER) is the largest organelle of the cell, composed of a continuous network of sheets and tubules, and is involved in protein, calcium (Ca2+ ) and lipid homeostasis. In neurons, the ER extends throughout the cell, both somal and axodendritic compartments, and is highly important for neuronal functions. A third of the proteome of a cell, secreted and membrane-bound proteins, are processed within the ER lumen and most of these proteins are vital for neuronal activity. The brain itself is high in lipid content and many structural lipids are produced, in part, by the ER...
May 1, 2023: Pharmacological Reviews
https://read.qxmd.com/read/36918259/g-protein-coupled-receptor-pharmacology-insights-from-mass-spectrometry
#30
REVIEW
Hsin-Yung Yen, Ali Jazayeri, Carol V Robinson
G protein-coupled receptors (GPCRs) are key drug targets due to their involvement in many physiological processes. The complexity of receptor pharmacology, however, is influenced by multiple interactions with various types of ligands and protein transducers representing significant challenges for drug discovery. The ability of mass spectrometry (MS) to observe both the binding of ligand molecules, such as lipids, ions, or drugs, and their impact on interaction with transducers provides an exciting opportunity to probe many aspects that are difficult to track directly in cell-based systems...
May 2023: Pharmacological Reviews
https://read.qxmd.com/read/36973040/-abcb1-and-abcg2-regulation-at-the-blood-brain-barrier-potential-new-targets-to-improve-brain-drug-delivery
#31
JOURNAL ARTICLE
Julia A Schulz, Anika M S Hartz, Björn Bauer
The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat CNS diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solve this clinical problem. In this comprehensive review, we summarize current knowledge on signaling pathways that regulate ABCB1/ABCG2 at the blood-brain barrier...
March 27, 2023: Pharmacological Reviews
https://read.qxmd.com/read/36931724/review-of-natural-language-processing-in-pharmacology
#32
JOURNAL ARTICLE
Dimitar Trajanov, Vangel Trajkovski, Makedonka Dimitrieva, Jovana Dobreva, Milos Jovanovik, Matej Klemen, Aleš Žagar, Marko Robnik-Šikonja
Natural language processing (NLP) is an area of artificial intelligence that applies information technologies to process the human language, understand it to a certain degree, and use it in various applications. This area has rapidly developed in the last few years and now employs modern variants of deep neural networks to extract relevant patterns from large text corpora. The main objective of this work is to survey the recent use of NLP in the field of pharmacology. As our work shows, NLP is a highly relevant information extraction and processing approach for pharmacology...
March 17, 2023: Pharmacological Reviews
https://read.qxmd.com/read/36927888/-pharmacogenomics-driving-personalized-medicine
#33
JOURNAL ARTICLE
Wolfgang Sadee, Danxin Wang, Katherine Hartmann, Amanda Ewart Toland
Personalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool to improve outcomes and prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all 'omics' fields, e.g., proteomics, transcriptomics, metabolomics, and metagenomics. This review summarizes basic genomics principles relevant to translation into therapies, assessing pharmacogenomics' central role in converging diverse elements of personalized medicine...
March 16, 2023: Pharmacological Reviews
https://read.qxmd.com/read/36918260/-potassium-channels-in-parkinson-s-disease-potential-roles-in-its-pathogenesis-and-innovative-molecular-targets-for-treatment
#34
JOURNAL ARTICLE
Xiaoyi Chen, Yunjiang Feng, Ronald J Quinn, Dean L Pountney, Des R Richardson, George D Mellick, Linlin Ma
Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the midbrain. The loss of neurons results in a subsequent reduction of dopamine in the striatum, which underlies the core motor symptoms of PD. To date, there are no effective treatments to stop, slow, or reverse the pathological progression of dopaminergic neurodegeneration. This unfortunate predicament is because of the current early stages in understanding the biological targets and pathways involved in PD pathogenesis...
March 14, 2023: Pharmacological Reviews
https://read.qxmd.com/read/36792365/pharmacology-of-heparin-and-related-drugs-an-update
#35
REVIEW
John Hogwood, Barbara Mulloy, Rebeca Lever, Elaine Gray, Clive P Page
Heparin has been used extensively as an antithrombotic and anticoagulant for close to 100 years. This anticoagulant activity is attributed mainly to the pentasaccharide sequence, which potentiates the inhibitory action of antithrombin, a major inhibitor of the coagulation cascade. More recently it has been elucidated that heparin exhibits anti-inflammatory effect via interference of the formation of neutrophil extracellular traps and this may also contribute to heparin's antithrombotic activity. This illustrates that heparin interacts with a broad range of biomolecules, exerting both anticoagulant and nonanticoagulant actions...
March 2023: Pharmacological Reviews
https://read.qxmd.com/read/36781219/newly-developed-targeted-therapies-against-the-androgen-receptor-in-triple-negative-breast-cancer-a-review
#36
REVIEW
Edris Choupani, Mohammad Mahmoudi Gomari, Saeed Zanganeh, Sherko Nasseri, Kaveh Haji-Allahverdipoor, Neda Rostami, Yaeren Hernandez, Safa Najafi, Neda Saraygord-Afshari, Arshad Hosseini
Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC...
March 2023: Pharmacological Reviews
https://read.qxmd.com/read/36781218/targeting-persistent-changes-in-neuroimmune-and-epigenetic-signaling-in-adolescent-drinking-to-treat-alcohol-use-disorder-in-adulthood
#37
REVIEW
Fulton T Crews, Leon G Coleman, Victoria A Macht, Ryan P Vetreno
Studies universally find early age of drinking onset is linked to lifelong risks of alcohol problems and alcohol use disorder (AUD). Assessment of the lasting effect of drinking during adolescent development in humans is confounded by the diversity of environmental and genetic factors that affect adolescent development, including emerging personality disorders and progressive increases in drinking trajectories into adulthood. Preclinical studies using an adolescent intermittent ethanol (AIE) exposure rat model of underage binge drinking avoid the human confounds and support lifelong changes that increase risks...
March 2023: Pharmacological Reviews
https://read.qxmd.com/read/36781217/sex-gender-differences-in-the-time-course-for-the-development-of-substance-use-disorder-a-focus-on-the-telescoping-effect
#38
REVIEW
Eleanor Blair Towers, Ivy L Williams, Emaan I Qillawala, Emilie F Rissman, Wendy J Lynch
Sex/gender effects have been demonstrated for multiple aspects of addiction, with one of the most commonly cited examples being the "telescoping effect" where women meet criteria and/or seek treatment of substance use disorder (SUD) after fewer years of drug use as compared with men. This phenomenon has been reported for multiple drug classes including opioids, psychostimulants, alcohol, and cannabis, as well as nonpharmacological addictions, such as gambling. However, there are some inconsistent reports that show either no difference between men and women or opposite effects and a faster course to addiction in men than women...
March 2023: Pharmacological Reviews
https://read.qxmd.com/read/36781216/pharmacological-targeting-of-mitochondria-in-diabetic-kidney-disease
#39
REVIEW
Kristan H Cleveland, Rick G Schnellmann
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in the United States and many other countries. DKD occurs through a variety of pathogenic processes that are in part driven by hyperglycemia and glomerular hypertension, leading to gradual loss of kidney function and eventually progressing to ESRD. In type 2 diabetes, chronic hyperglycemia and glomerular hyperfiltration leads to glomerular and proximal tubular dysfunction. Simultaneously, mitochondrial dysfunction occurs in the early stages of hyperglycemia and has been identified as a key event in the development of DKD...
March 2023: Pharmacological Reviews
https://read.qxmd.com/read/36732079/-cellular-senescence-from-mechanisms-to-current-biomarkers-and-senotherapies
#40
JOURNAL ARTICLE
Vasco Lucas, Cláudia Cavadas, Célia Alexandra Aveleira
An increase in life expectancy in developed countries has led to an insurgency of chronic aging-related diseases. In the last few decades, several studies provided evidence of the prominent role of cellular senescence in many of these pathologies. Key traits of senescent cells include cell cycle arrest, apoptosis resistance, and secretome shift to senescence-associated secretory phenotype (SASP) resulting in increased secretion of various intermediate bioactive factors important for senescence pathophysiology...
February 2, 2023: Pharmacological Reviews
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