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State-of-the-Art Molecular Pharmacology in USA

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 11879

Special Issue Editors


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Collection Editor
Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, USA
Interests: cardiovascular G protein-coupled receptors (GPCRs); heart failure; autonomic control of the circulation; adrenal physiology and pharmacology; adrenergic receptors; angiotensin receptors; signal transduction; gene therapy; aldosterone pharmacology; GPCR-Kinases; arrestins; G protein signaling
Special Issues, Collections and Topics in MDPI journals

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Collection Editor
1. Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, 5920 Forest Park Avenue, Dallas, TX, USA
2. Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 5920 Forest Park Avenue, Dallas, TX, USA
Interests: clinical pharmacology; drug discovery; drug development; drug regulatory affairs; biomarker discovery; altered metabolism of disease states; advanced analytical techniques
Special Issues, Collections and Topics in MDPI journals

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Collection Editor
Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USA
Interests: cancer therapeutics; nitric oxide; hydrogen sulfide; cell signaling; resolution
Special Issues, Collections and Topics in MDPI journals

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Collection Editor
UNM Health Sciences Center, Albuquerque, NM, USA
Interests: acute kidney injury; polyamine catabolism; polyamines; Tuberous Sclerosis Complex (TSC); TSC renal cystic disease

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Collection Editor
1. Department of Medicine, Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York, NY 10461, USA
2. Department of Advanced Biomedical Science, “Federico II” University, International Translational Research and Medical Education Consortium (ITME), 80131 Naples, Italy
3. Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, NY 10461, USA
Interests: cardiology; hypertension; restenosis; heart failure; myocardial infarction; endothelial dysfunction; mitochondria; diabetes; microRNAs; insulin resistance; atherosclerosis; thrombosis; cardiac hypertrophy; pancreatic beta cell function; insulin release
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmacology is a discipline that deals with the interactions between natural, semisynthetic, or fully (bio)synthetic therapeutic agents at the cellular and organismal levels. These therapeutic agents can be small molecules or macromolecules, such as proteins and antibodies. Thus, this subject is positioned at the interface of pharmacy/chemistry and physiology/pathophysiology in their broadest senses. It operates at various organizational levels, such as the molecular, subcellular, cellular, organ, and systemic platforms. Molecular pharmacology investigates the molecular mode of action of therapeutic agents using cellular, genetic, and molecular biology approaches, and is among the most rapidly developing fields of pharmacology.

Original research and review articles on molecular pharmacology are invited. The “Molecular Pharmacology” Section aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to study drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level.

A great number of research teams in the USA from different institutions and universities are working together and devoting considerable effort to developing and studying molecular pharmacology. This Topical Collection is committed to providing an overview of the macromolecular sciences and technologies in the USA.

Dr. Anastasios Lymperopoulos
Prof. Dr. William C. (Trey) Putnam
Prof. Dr. Khosrow Kashfi
Dr. Kamyar Zahedi
Prof. Dr. Gaetano Santulli
Collection Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • signal transduction
  • receptor
  • animal models
  • preclinical
  • pharmacodynamics
  • pharmacokinetics
  • drug development
  • drug metabolism

Published Papers (4 papers)

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Research

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11 pages, 1953 KiB  
Article
miR-142 Targets TIM-1 in Human Endothelial Cells: Potential Implications for Stroke, COVID-19, Zika, Ebola, Dengue, and Other Viral Infections
by Urna Kansakar, Jessica Gambardella, Fahimeh Varzideh, Roberta Avvisato, Stanislovas S. Jankauskas, Pasquale Mone, Alessandro Matarese and Gaetano Santulli
Int. J. Mol. Sci. 2022, 23(18), 10242; https://doi.org/10.3390/ijms231810242 - 6 Sep 2022
Cited by 14 | Viewed by 2705
Abstract
T-cell immunoglobulin and mucin domain 1 (TIM-1) has been recently identified as one of the factors involved in the internalization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells, in addition to angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 [...] Read more.
T-cell immunoglobulin and mucin domain 1 (TIM-1) has been recently identified as one of the factors involved in the internalization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells, in addition to angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), neuropilin-1, and others. We hypothesized that specific microRNAs could target TIM-1, with potential implications for the management of patients suffering from coronavirus disease 2019 (COVID-19). By combining bioinformatic analyses and functional assays, we identified miR-142 as a specific regulator of TIM-1 transcription. Since TIM-1 has been implicated in the regulation of endothelial function at the level of the blood-brain barrier (BBB) and its levels have been shown to be associated with stroke and cerebral ischemia-reperfusion injury, we validated miR-142 as a functional modulator of TIM-1 in human brain microvascular endothelial cells (hBMECs). Taken together, our results indicate that miR-142 targets TIM-1, representing a novel strategy against cerebrovascular disorders, as well as systemic complications of SARS-CoV-2 and other viral infections. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in USA)
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13 pages, 3488 KiB  
Article
Expanded Potential of the Polyamine Analogue SBP-101 (Diethyl Dihydroxyhomospermine) as a Modulator of Polyamine Metabolism and Cancer Therapeutic
by Cassandra E. Holbert, Jackson R. Foley, Tracy Murray Stewart and Robert A. Casero, Jr.
Int. J. Mol. Sci. 2022, 23(12), 6798; https://doi.org/10.3390/ijms23126798 - 18 Jun 2022
Cited by 8 | Viewed by 2651
Abstract
Naturally occurring polyamines are absolutely required for cellular growth and proliferation. Many neoplastic cells are reliant on elevated polyamine levels and maintain these levels through dysregulated polyamine metabolism. The modulation of polyamine metabolism is thus a promising avenue for cancer therapeutics and has [...] Read more.
Naturally occurring polyamines are absolutely required for cellular growth and proliferation. Many neoplastic cells are reliant on elevated polyamine levels and maintain these levels through dysregulated polyamine metabolism. The modulation of polyamine metabolism is thus a promising avenue for cancer therapeutics and has been attempted with numerous molecules, including enzyme inhibitors and polyamine analogues. SBP-101 (diethyl dihydroxyhomospermine) is a spermine analogue that has shown efficacy in slowing pancreatic tumor progression both in vitro and in vivo; however, the mechanisms underlying these effects remain unclear. We determined the effects of the SBP-101 treatment on a variety of cancer cell types in vitro, including lung, pancreatic, and ovarian. We evaluated the activity of enzymes involved in polyamine metabolism and the effect on intracellular polyamine pools following the SBP-101 treatment. The SBP-101 treatment produced a modest but variable increase in polyamine catabolism; however, a robust downregulation of the activity of the biosynthetic enzyme, ornithine decarboxylase (ODC), was seen across all of the cell types studied and indicates that SBP-101 likely exerts its effect predominately through the downregulation of ODC, with a minor upregulation of catabolism. Our in vitro work indicated that SBP-101 was most toxic in the tested ovarian cell lines. Therefore, we evaluated the efficacy of SBP-101 as a monotherapy in the immunosuppressive VDID8+ murine ovarian model. Mice treated with SBP-101 demonstrated a delay in tumor progression, a decrease in the overall tumor burden, and a marked increase in median survival. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in USA)
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14 pages, 3071 KiB  
Article
Dysregulation of S-adenosylmethionine Metabolism in Nonalcoholic Steatohepatitis Leads to Polyamine Flux and Oxidative Stress
by Connor Quinn, Mario C. Rico, Carmen Merali and Salim Merali
Int. J. Mol. Sci. 2022, 23(4), 1986; https://doi.org/10.3390/ijms23041986 - 11 Feb 2022
Cited by 12 | Viewed by 2696
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease worldwide, with 25% of these patients developing nonalcoholic steatohepatitis (NASH). NASH significantly increases the risk of cirrhosis and decompensated liver failure. Past studies in rodent models have shown that [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease worldwide, with 25% of these patients developing nonalcoholic steatohepatitis (NASH). NASH significantly increases the risk of cirrhosis and decompensated liver failure. Past studies in rodent models have shown that glycine-N-methyltransferase (GNMT) knockout results in rapid steatosis, fibrosis, and hepatocellular carcinoma progression. However, the attenuation of GNMT in subjects with NASH and the molecular basis for its impact on the disease process is still unclear. To address this knowledge gap, we show the reduction of GNMT protein levels in the liver of NASH subjects compared to healthy controls. To gain insight into the impact of decreased GNMT in the disease process, we performed global label-free proteome studies on the livers from a murine modified amylin diet-based model of NASH. Histological and molecular characterization of the animal model demonstrate a high resemblance to human disease. We found that a reduction of GNMT leads to a significant increase in S-adenosylmethionine (AdoMet), an essential metabolite for transmethylation reactions and a substrate for polyamine synthesis. Further targeted proteomic and metabolomic studies demonstrated a decrease in GNMT transmethylation, increased flux through the polyamine pathway, and increased oxidative stress production contributing to NASH pathogenesis. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in USA)
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Review

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14 pages, 316 KiB  
Review
Intestinal Enteroendocrine Cells: Present and Future Druggable Targets
by Roger Atanga, Varsha Singh and Julie G. In
Int. J. Mol. Sci. 2023, 24(10), 8836; https://doi.org/10.3390/ijms24108836 - 16 May 2023
Cited by 6 | Viewed by 2661
Abstract
Enteroendocrine cells are specialized secretory lineage cells in the small and large intestines that secrete hormones and peptides in response to luminal contents. The various hormones and peptides can act upon neighboring cells and as part of the endocrine system, circulate systemically via [...] Read more.
Enteroendocrine cells are specialized secretory lineage cells in the small and large intestines that secrete hormones and peptides in response to luminal contents. The various hormones and peptides can act upon neighboring cells and as part of the endocrine system, circulate systemically via immune cells and the enteric nervous system. Locally, enteroendocrine cells have a major role in gastrointestinal motility, nutrient sensing, and glucose metabolism. Targeting the intestinal enteroendocrine cells or mimicking hormone secretion has been an important field of study in obesity and other metabolic diseases. Studies on the importance of these cells in inflammatory and auto-immune diseases have only recently been reported. The rapid global increase in metabolic and inflammatory diseases suggests that increased understanding and novel therapies are needed. This review will focus on the association between enteroendocrine changes and metabolic and inflammatory disease progression and conclude with the future of enteroendocrine cells as potential druggable targets. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in USA)
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