scholarly journals Introduction to the Theme “New Insights, Strategies, and Therapeutics for Common Diseases”

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Paul A. Insel ◽  
Terrence F. Blaschke ◽  
Susan G. Amara ◽  
Urs A. Meyer
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Strategies ◽  
Drug Formulation ◽  
Annual Review ◽  
Publication Date ◽  
Diverse Range ◽  
Common Diseases ◽  
Pharmacology And Toxicology ◽  
Patient Centric

The reviews in Volume 62 of the Annual Review of Pharmacology and Toxicology ( ARPT) cover a diverse range of topics. A theme that encompasses many of these reviews is their relevance to common diseases and disorders, including type 2 diabetes, heart failure, cancer, tuberculosis, Alzheimer's disease, neurodegenerative disorders, and Down syndrome. Other reviews highlight important aspects of therapeutics, including placebos and patient-centric approaches to drug formulation. The reviews with this thematic focus, as well as other reviews in this volume, emphasize new mechanistic insights, experimental and therapeutic strategies, and novel insights regarding topics in the disciplines of pharmacology and toxicology. As the editors of ARPT, we believe that these reviews help advance those disciplines and, even more importantly, have the potential to improve the health care of the world's population. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

COVID-19 and Diabetes

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Awadhesh Kumar Singh ◽  
Kamlesh Khunti
Keyword(s):  
Conclusive Evidence ◽  
Annual Review ◽  
Publication Date ◽  
Β Cells ◽  
Oral Antidiabetic Agents ◽  
Randomized Controlled ◽  
Conclusive Data ◽  
New Onset

The prevalence of diabetes in people with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has varied worldwide. Most of the available evidence suggests a significant increase in severity and mortality of COVID-19 in people with either type 1 (T1DM) or type 2 diabetes mellitus (T2DM), especially in association with poor glycemic control. While new-onset hyperglycemia and new-onset diabetes (both T1DM and T2DM) have been increasingly recognized in the context of COVID-19 and have been associated with worse outcome, no conclusive evidence yet suggests direct tropism of SARS-CoV-2 on the β cells of pancreatic islets. While all approved oral antidiabetic agents appear to be safe in people with T2DM having COVID-19, no conclusive data are yet available to indicate a mortality benefit with any class of these drugs, in the absence of large randomized controlled trials. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Long Noncoding RNAs and Human Liver Disease

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Johanna K. DiStefano ◽  
Glenn S. Gerhard
Keyword(s):  
Liver Disease ◽  
Biological Significance ◽  
Noncoding Rnas ◽  
Classification Systems ◽  
Long Noncoding Rnas ◽  
Annual Review ◽  
Publication Date ◽  
Cholestatic Liver Disease ◽  
Diverse Range ◽  
Number Of Publications

Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Measuring Pharmacogene Variant Function at Scale Using Multiplexed Assays

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Renee C. Geck ◽  
Gabriel Boyle ◽  
Clara J. Amorosi ◽  
Douglas M. Fowler ◽  
Maitreya J. Dunham
Keyword(s):  
Next Generation Sequencing ◽  
Functional Data ◽  
Genetic Variants ◽  
Genetic Information ◽  
Annual Review ◽  
Publication Date ◽  
Drug Selection ◽  
Functional Consequences ◽  
Pharmacology And Toxicology ◽  
Generation Sequencing

As costs of next-generation sequencing decrease, identification of genetic variants has far outpaced our ability to understand their functional consequences. This lack of understanding is a central challenge to a key promise of pharmacogenomics: using genetic information to guide drug selection and dosing. Recently developed multiplexed assays of variant effect enable experimental measurement of the function of thousands of variants simultaneously. Here, we describe multiplexed assays that have been performed on nearly 25,000 variants in eight key pharmacogenes ( ADRB2, CYP2C9, CYP2C19, NUDT15, SLCO1B1, TMPT, VKORC1, and the LDLR promoter), discuss advances in experimental design, and explore key challenges that must be overcome to maximize the utility of multiplexed functional data. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Benjamin Steinhorn ◽  
Emrah Eroglu ◽  
Thomas Michel
Keyword(s):  
Dynamic Control ◽  
Cardiovascular Pharmacology ◽  
Redox Balance ◽  
Signaling Molecules ◽  
Annual Review ◽  
Publication Date ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Pharmacology And Toxicology ◽  
Intracellular Redox

Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Defining and Classifying New Subgroups of Diabetes

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Ashok Balasubramanyam
Keyword(s):  
Neonatal Diabetes ◽  
Large Datasets ◽  
Annual Review ◽  
Publication Date ◽  
Maturity Onset Diabetes ◽  
Bioinformatic Approaches ◽  
Complex Forms

An etiologically based classification of diabetes is needed to account for the heterogeneity of type 1 and type 2 diabetes (T1D and T2D) and emerging forms of diabetes worldwide. It may be productive for both classification and clinical discovery to consider variant forms of diabetes as a spectrum. Maturity onset diabetes of youth and neonatal diabetes serve as models for etiologically defined, rare forms of diabetes in the spectrum. Ketosis-prone diabetes is a model for more complex forms, amenable to phenotypic dissection. Bioinformatic approaches such as clustering analyses of large datasets and multi-omics investigations of rare and atypical phenotypes are promising avenues to explore and define new subgroups of diabetes. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Introduction to the Theme “New Therapeutic Targets”

2019 ◽  
Vol 59 (1) ◽  
pp. 15-20
Author(s):  
Paul A. Insel ◽  
Susan G. Amara ◽  
Terrence F. Blaschke ◽  
Urs A. Meyer
Keyword(s):  
Chronic Renal Disease ◽  
Therapeutic Targets ◽  
Annual Review ◽  
Post Traumatic Stress ◽  
Thyroid Associated Ophthalmopathy ◽  
Post Traumatic ◽  
Pharmacology And Toxicology ◽  
New Therapeutic Targets ◽  
Novel Therapeutic

“New Therapeutic Targets” is the theme of articles in the Annual Review of Pharmacology and Toxicology, Volume 59. Reviews in this volume discuss targets for a variety of conditions in need of new therapies, including type 2 diabetes, heart failure with preserved ejection fraction, obesity, thyroid-associated ophthalmopathy, tinnitus, multiple sclerosis, Parkinson's disease and other neurodegenerative diseases, pain, depression, post-traumatic stress disorder, muscle wasting diseases, cancer, and anemia associated with chronic renal disease. Numerous articles in this volume focus on the identification, validation, and utility of novel therapeutic targets, in particular, ones that involve new or unexpected molecular entities. This theme complements several previous themes, including “New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development,” “Precision Medicine and Prediction in Pharmacology,” and “New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology.”

The Gut Microbiome, Metformin, and Aging

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Sri Nitya Reddy Induri ◽  
Payalben Kansara ◽  
Scott C. Thomas ◽  
Fangxi Xu ◽  
Deepak Saxena ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Healthy Aging ◽  
Bacterial Species ◽  
Annual Review ◽  
Publication Date ◽  
Low Grade ◽  
Host Interactions ◽  
Age Related ◽  
Low Grade Inflammation

Metformin has been extensively used for the treatment of type 2 diabetes, and it may also promote healthy aging. Despite its widespread use and versatility, metformin's mechanisms of action remain elusive. The gut typically harbors thousands of bacterial species, and as the concentration of metformin is much higher in the gut as compared to plasma, it is plausible that microbiome-drug-host interactions may influence the functions of metformin. Detrimental perturbations in the aging gut microbiome lead to the activation of the innate immune response concomitant with chronic low-grade inflammation. With the effectiveness of metformin in diabetes and antiaging varying among individuals, there is reason to believe that the gut microbiome plays a role in the efficacy of metformin. Metformin has been implicated in the promotion and maintenance of a healthy gut microbiome and reduces many age-related degenerative pathologies. Mechanistic understanding of metformin in the promotion of a healthy gut microbiome and aging will require a systems-level approach. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma

2021 ◽  
Vol 39 (1) ◽  
Author(s):  
Noe Rodriguez-Rodriguez ◽  
Mayuri Gogoi ◽  
Andrew N.J. McKenzie
Keyword(s):  
Allergic Asthma ◽  
Cell Activation ◽  
Innate Lymphoid Cells ◽  
Experimental Models ◽  
Lymphoid Cells ◽  
Annual Review ◽  
Publication Date ◽  
Effector Cytokines ◽  
Group 2

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then disseminating cytokine cues to elicit effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Thioredoxin Reductase Inhibition for Cancer Therapy

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Radosveta Gencheva ◽  
Elias S.J. Arnér
Keyword(s):  
Cancer Therapy ◽  
Thioredoxin Reductase ◽  
Normal Activity ◽  
Annual Review ◽  
Publication Date ◽  
Nadph Oxidases ◽  
Thioredoxin Reductase 1 ◽  
Wide Range ◽  
Oxidative Challenge ◽  
Pharmacology And Toxicology

The cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, TXNRD1), and to some extent mitochondrial TrxR2 (TXNRD2), can be inhibited by a wide range of electrophilic compounds. Many such compounds also yield cytotoxicity toward cancer cells in culture or in mouse models, and most compounds are likely to irreversibly modify the easily accessible selenocysteine residue in TrxR1, thereby inhibiting its normal activity to reduce cytosolic thioredoxin (Trx1, TXN) and other substrates of the enzyme. This leads to an oxidative challenge. In some cases, the inhibited forms of TrxR1 are not catalytically inert and are instead converted to prooxidant NADPH oxidases, named SecTRAPs, thus further aggravating the oxidative stress, particularly in cells expressing higher levels of the enzyme. In this review, the possible molecular and cellular consequences of these effects are discussed in relation to cancer therapy, with a focus on outstanding questions that should be addressed if targeted TrxR1 inhibition is to be further developed for therapeutic use. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Endocannabinoid-Based Therapies

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Daniele Piomelli ◽  
Alex Mabou Tagne
Keyword(s):  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Annual Review ◽  
Publication Date ◽  
Metabolizing Enzymes ◽  
Pharmacological Agents ◽  
Surface Receptors ◽  
Signaling Complex ◽  
Therapeutic Drugs ◽  
Pharmacology And Toxicology

The endocannabinoids are lipid-derived messengers that play a diversity of regulatory roles in mammalian physiology. Dysfunctions in their activity have been implicated in various disease conditions, attracting attention to the endocannabinoid system as a possible source of therapeutic drugs. This signaling complex has three components: the endogenous ligands, anandamide and 2-arachidonoyl- sn-glycerol (2-AG); a set of enzymes and transporters that generate, eliminate, or modify such ligands; and selective cell surface receptors that mediate their biological actions. We provide an overview of endocannabinoid formation, deactivation, and biotransformation and outline the properties and therapeutic potential of pharmacological agents that interfere with those processes. We describe small-molecule inhibitors that target endocannabinoid-producing enzymes, carrier proteins that transport the endocannabinoids into cells, and intracellular endocannabinoid-metabolizing enzymes. We briefly discuss selected agents that simultaneously interfere with components of the endocannabinoid system and with other functionally related signaling pathways. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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