Review
Physiology
Fulye Argunhan, Susan D. Brain
Summary: The treatment of hypertension and heart failure is a major challenge, with over 26 million people affected worldwide. CGRP has been found to have beneficial effects in hypertensive and heart failure patients. However, due to its short half-life, the beneficial effects of CGRP are often acute and transient. Recently developed long-lasting CGRP agonists may provide a solution for further studying CGRP in cardiovascular disease.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Tatsiana Suvorava, Sara Metry, Stephanie Pick, Georg Kojda
Summary: Vascular tone regulation by nitric oxide is a crucial physiological function, with endothelial dysfunction potentially being an underlying cause of hypertension. Increasing eNOS activity reduces blood pressure, while decreasing activity has the opposite effect. These findings have important implications for pre-hypertensive treatment.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Kamrouz Ghadimi, Jhaymie L. Cappiello, Mary Cooter Wright, Jerrold H. Levy, Benjamin S. Bryner, Adam D. Devore, Jacob N. Schroder, Chetan B. Patel, Sudarshan Rajagopal, Svati H. Shah, Carmelo A. Milano
Summary: In patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO.
Review
Chemistry, Medicinal
Noemi M. Atucha, Paola Romecin, Felix Vargas, Joaquin Garcia-Estan
Summary: Flavonoids are plant-derived substances with various beneficial effects on human health. Their importance in diet has been highlighted by numerous studies, which have demonstrated the positive effects of flavonols and flavones on cardiovascular health, including a lower risk of cardiovascular diseases. This mini-review focuses on the antihypertensive effects of flavonoids and their role in arterial hypertension.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jennifer Q. J. Zhang, Sayanthooran Saravanabavan, Kai Man Cheng, Aarya Raghubanshi, Ashley N. Chandra, Alexandra Munt, Benjamin Rayner, Yunjia Zhang, Katrina Chau, Annette T. Y. Wong, Gopala K. Rangan
Summary: The study found that L-arginine has a mild direct effect on reducing renal cyst growth in vitro, while long-term sodium nitrate supplementation was ineffective in vivo. This suggests that the bioconversion of dietary nitrate to NO through the entero-salivary pathway may not be sufficient to influence the progression of renal cyst growth in ADPKD.
Review
Biochemistry & Molecular Biology
Marharyta Semenikhina, Mariia Stefanenko, Denisha R. Spires, Dania Ilatovskaya, Oleg Palygin
Summary: Nitric oxide (NO) is an important signaling molecule in the kidney, involved in various physiological and pathophysiological processes. However, the mechanisms of NO production and release in glomerular cells, particularly podocytes, are not well understood. Changes in NO availability have been implicated in diseases such as hypertension and diabetes. Further investigation into these mechanisms will help in developing strategies to prevent or manage kidney damage.
Review
Pharmacology & Pharmacy
Elizabeth C. Cottrell
Summary: Hypertension in pregnancy is common and poses risks for mothers and babies. Current treatments are limited, so new approaches are needed. Dietary nitrate supplementation has shown potential benefits for hypertension, but more research is needed.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Clinical Neurology
T. Michael De Silva, Mary L. Modrick, Justin L. Grobe, Frank M. Faraci
Summary: The activation of central and cerebrovascular RAS impairs endothelial signaling in the brain through AT1R expression and activation, leading to impaired cerebral artery function and showing sex-dependent effects.
Article
Peripheral Vascular Disease
Jie Zhang, Ximing Wang, Yu Cui, Shan Jiang, Jin Wei, Jenna Chan, Anish Thalakola, Thanh Le, Lan Xu, Liang Zhao, Lei Wang, Kun Jiang, Feng Cheng, Trushar Patel, Jacentha Buggs, Volker Vallon, Ruisheng Liu
Summary: This study investigates the mechanism of hypertension in patients with diabetes and suggests that in early diabetes, upregulation of NOS1 in the macula densa plays a role in inhibiting TGF and increasing glomerular filtration rate, which helps in maintaining normal blood pressure.
Article
Gastroenterology & Hepatology
Songling Liu, Richard T. Premont, Ki-Hoon Park, Don C. Rockey
Summary: The distribution of beta-PIX in the liver is mainly restricted to sinusoidal endothelial cells, where it forms a signaling module with GIT1 and eNOS, playing a critical role in stimulating eNOS activity. Disruption of beta-PIX or GIT1 leads to reduced eNOS activity, and specific molecular domains in GIT1 and beta-PIX are important in regulating eNOS activity.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yoogyeong Oh, Kyungtae Park, Sungwon Jung, Moonhyun Choi, Taihyun Kim, Yoojin Lee, Jae Young Choi, Yang-Hee Kim, Se Yong Jung, Jinkee Hong
Summary: In this study, open porous nitric oxide (NO) inhalers (OPNIs) with highly porous structures are synthesized to deliver nanomolar NO deep into the lungs through a nebulizer. The OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release, suggesting their potential as tools for pulmonary arterial hypertension (PAH) treatment.
Article
Pediatrics
Yanling Tan, Sa Wang, Xinrui Ren, Chao Zhang, Feng Xu
Summary: Endogenous hydrogen sulfide and nitric oxide levels are closely associated with CHD-PAH incidence, and there is a correlation between endogenous hydrogen sulfide levels and the postoperative prognosis of CHD in children. Higher hydrogen sulfide concentrations seem to correspond to better patient prognosis, serving as an early prognostic index, and guiding treatment efforts to improve outcomes among children with CHD-PAH.
EUROPEAN JOURNAL OF PEDIATRICS
(2021)
Article
Cardiac & Cardiovascular Systems
Michal Schafer, Benjamin S. Frank, D. Dunbar Ivy, Steven H. Abman, Kurt R. Stenmark, Max B. Mitchell, Lorna P. Browne, Alex J. Barker, Kendall S. Hunter, Vitaly Kheyfets, Kathleen Miller-Reed, Richard Ing, Gareth J. Morgan, Uyen Truong
Summary: In this study, 4-dimensional-flow magnetic resonance imaging and standard catheterization were used to evaluate intracardiac flow dynamics in children with PAH during inhaled nitric oxide (iNO) challenge. The results showed significant improvement in right ventricular (RV) flow efficiency on iNO administration, with no change in the left ventricle. Despite minimal changes in catheterization hemodynamics, alterations in RV flow were observed, suggesting that flow hemodynamic evaluation may offer more quantitative insights into vasoreactivity testing in PAH.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Medicine, General & Internal
Yiwei Liu, Yifan Zhu, Chenyu Jiang, Zhanhao Su, Yi Yan, Bei Feng, Wen Mao, Yuyan Zhang, Xiaojian Wang, Zhuoming Xu, Hao Zhang
Summary: This study developed a novel portable device to produce nitric oxide (NO) for in-home inhalation therapy in patients with pulmonary artery hypertension (PAH). The device effectively reduced pulmonary arterial pressure and pulmonary vascular resistance in a pig model of PAH without causing major physiologic disruptions. This research paves the way for future clinical trials in PAH patients and other cardiopulmonary conditions.
Review
Biochemistry & Molecular Biology
Maria Carmela Cerra, Mariacristina Filice, Alessia Caferro, Rosa Mazza, Alfonsina Gattuso, Sandra Imbrogno
Summary: Aquatic animals are facing increasing challenges due to fluctuations in oxygen levels caused by global warming and eutrophication. Teleost fish, such as species from the Cyprinidae family, demonstrate species-specific adaptability to low oxygen environments. These fish have developed unique mechanisms to preserve cardiac function, allowing them to survive in low oxygen conditions. By studying these adaptations, researchers can gain insights into functional changes and molecular events in the fish heart, with potential applications in environmental management and decision making.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Martina Salerno, Carmine Varricchio, Federica Bevilacqua, Dirk Jochmans, Johan Neyts, Andrea Brancale, Salvatore Ferla, Marcella Bassetto
Summary: Different viruses, such as enterovirus 71, rely on the host enzyme METTL3 to complete their cytoplasmic life cycle stages. By modulating the activity of this enzyme, it is possible to interfere with a broad range of viral infections. In this study, a series of nucleoside analogues were designed as inhibitors of human METTL3 to target multiple viral infections. Through molecular docking studies and synthesis, several novel and potent inhibitors of enterovirus 71 were identified.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Thibault Alle, Carmine Varricchio, Yuemang Yao, Bobby Lucero, Goodwell Nzou, Stefania Demuro, Megan Muench, Khoa D. Vuong, Killian Oukoloff, Anne-Sophie Cornec, Karol R. Francisco, Conor R. Caffrey, Virginia M. -Y. Lee, Amos B. Smith III, Andrea Brancale, Kurt R. Brunden, Carlo Ballatore
Summary: Researchers designed, synthesized, and evaluated a series of new triazolo[1,5-a]-pyrimidine compounds, and further elucidated the structure-activity relationships of these compounds through matched molecular pair analyses and computational studies. The study identified novel microtubule-stabilizing triazolo[1,5-a]-pyrimidine candidates that exhibited favorable ADME-PK properties, including brain penetration and oral bioavailability, as well as brain pharmacodynamic activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Gilda Giancotti, Giulio Nannetti, Gilda Padalino, Martina Landini, Nanci Santos-Ferreira, Jana Van Dycke, Valentina Naccarato, Usheer Patel, Romano Silvestri, Johan Neyts, Roberto Gozalbo-Rovira, Jesus Rodriguez-Diaz, Joana Rocha-Pereira, Andrea Brancale, Salvatore Ferla, Marcella Bassetto
Summary: Human norovirus is the leading cause of foodborne diseases worldwide, resulting in severe acute gastroenteritis outbreaks and causing approximately 200,000 deaths in children in developing countries annually. Current treatment options are limited to supportive care, highlighting the urgent need for antiviral agents. In this study, we focused on the viral RNA-dependent RNA polymerase (RdRp) as a potential target for antiviral drug discovery. By rationally modifying identified scaffolds, we synthesized new compounds with improved inhibition of RdRp, providing a promising foundation for further optimization.
Review
Chemistry, Multidisciplinary
Fedora Grande, Giuseppina Ioele, Anna Caruso, Maria Antonietta Occhiuzzi, Hussein El-Kashef, Carmela Saturnino, Maria Stefania Sinicropi
Summary: Carbazole derivatives have garnered significant attention in medicinal chemistry due to their diverse range of biological and pharmacological properties, such as antibacterial, antitumor, antioxidant, and anti-inflammatory activities. They have shown therapeutic potential in the pathogenesis and development of diabetes by reducing oxidative stress, blocking adrenergic hyperactivation, preventing damage to pancreatic cells, and modulating carbohydrate metabolism. This survey provides a summary of the latest advances in synthetic and natural carbazole-containing compounds involved in diabetes pathways.
APPLIED SCIENCES-BASEL
(2023)
Article
Pharmacology & Pharmacy
Jessica R. Spengler, Stephen R. Welch, Jerome Deval, Brian G. Gentry, Andrea Brancale, Kara Carter, Jennifer Moffat, Chris Meier, Katherine L. Seley-Radtke, Luis M. Schang
Summary: The 35th International Conference on Antiviral Research (ICAR) was held in Seattle, Washington, USA, on March 21-25, 2022, and via an interactive remote meeting platform. This report provides an overview of the conference, summarizing presentations and key conclusions from researchers in various areas of antiviral research and development. The conference showcased efforts and advancements in the field and demonstrated the significant response to the ongoing pandemic while emphasizing the importance of future pandemic preparedness.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Physical
Haoyue Xiang, Salvatore Ferla, Carmine Varricchio, Andrea Brancale, Nicola L. Brown, Gary W. Black, Nicholas J. Turner, Daniele Castagnolo
Summary: Two enzymatic strategies were developed to oxidize 1,2,3,4-tetrahydroquinolines (THQs) and N-cyclopropyl-N-alkylanilines into quinolines and 2-quinolones, respectively. Whole cells and monoamine oxidase (MAO-N) enzymes were used for the biotransformation of THQs, while horseradish peroxidase (HRP)-catalyzed annulation/aromatization reaction followed by Fe-mediated oxidation was employed for the conversion of N-cyclopropyl-N-alkylanilines into 2-quinolone compounds.
Article
Cell Biology
Carmine Rocca, Anna De Bartolo, Rita Guzzi, Maria Caterina Crocco, Vittoria Rago, Naomi Romeo, Ida Perrotta, Ernestina Marianna De Francesco, Maria Grazia Muoio, Maria Concetta Granieri, Teresa Pasqua, Rosa Mazza, Loubna Boukhzar, Benjamin Lefranc, Jerome Leprince, Maria Eugenia Gallo Cantafio, Teresa Soda, Nicola Amodio, Youssef Anouar, Tommaso Angelone
Summary: Cardiac lipotoxicity is a major factor in cardiovascular complications during obesity. A small peptide (PSELT), derived from SELENOT, has been found to protect cardiomyocytes against lipotoxicity. PSELT counteracts cell death, oxidative stress, and lipid accumulation induced by palmitate, and it regulates mitochondrial function and ER network.
Article
Cell Biology
Marilena Kampa, Rosamaria Lappano, Fedora Grande, Bruno Rizzuti, Marcello Maggiolini, Elias Castanas, Yves Jacquot
Summary: This article discusses the interactions of estrogen receptor alpha (ER alpha) with various molecules. The 295-311 region of ER alpha is targeted by post-translational modifications and may play a crucial role in transcription control. In addition to other proteins, this region interacts with G-protein-coupled estrogen receptor (GPER). The corresponding peptide, ER alpha 17p, has shown promising therapeutic potential as a GPER modulator, inducing apoptosis and reducing tumor size in triple-negative breast tumor xenografts in mice.
Article
Chemistry, Medicinal
Maria Rosaria Perri, Michele Pellegrino, Mariangela Marrelli, Stefano Aquaro, Fabiola Cavaliere, Fedora Grande, Maria Antonietta Occhiuzzi, Carmine Lupia, Claudia-Crina Toma, Filomena Conforti, Giancarlo Statti
Summary: Stilbenoids are plant phytoalexin polyphenols known for their anti-inflammatory potential. In this study, pinosylvin, a naturally occurring molecule found in Pinus nigra subsp. laricio var. calabrica, was identified and compared with resveratrol for their in vitro anti-inflammatory activity. Pinosylvin exhibited significant inhibition of pro-inflammatory cytokines and NO mediator in stimulated cells, as well as downregulation of JAK2 and STAT3 proteins in the JAK/STAT signaling pathway. Molecular docking study confirmed the capability of pinosylvin to bind to the active site of JAK2.
Review
Medicine, Research & Experimental
Carmine Rocca, Teresa Soda, Ernestina Marianna De Francesco, Marco Fiorillo, Francesco Moccia, Giuseppe Viglietto, Tommaso Angelone, Nicola Amodio
Summary: There is a complex pathophysiological relationship between cardiovascular diseases and cancer. The optimal activity of mitochondria is crucial and regulated by quality control systems. Impaired mitochondrial quality control is involved in the development of heart diseases and cancer. Modulating mitochondrial homeostasis may be a promising therapeutic strategy for both cardiology and oncology.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Editorial Material
Medicine, General & Internal
Carmine Rocca, Tommaso Angelone
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Chemistry, Medicinal
Luis Queiros-Reis, Joao R. Mesquita, Andrea Brancale, Marcella Bassetto
Summary: This review discusses the fatty acid binding pocket (FABP) in the spike glycoprotein of SARS-CoV-2 and its ligands with antiviral activity. Compounds that stabilize the inactive conformation of the spike protein and reduce viral infectivity show potential for the development of broad-spectrum antiviral agents.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Environmental Sciences
Maria Luigia Vommaro, Caroline Zanchi, Tommaso Angelone, Anita Giglio, Joachim Kurtz
Summary: This study evaluated the effects of a commercial herbicide residue on the biological interaction between mealworm beetle and entomopathogenic fungus. The results showed that the herbicide residue had no significant effect on the survival of the beetles, but it may temporarily affect fungal germination. These findings raise questions about the compatibility of bioinsecticides with synthetic pesticides and the effects of herbicide residues on host-pathogen interactions.
ENVIRONMENTAL POLLUTION
(2023)
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)