Article
Biochemistry & Molecular Biology
Cheng Zhong, Minze Xu, Senguel Boral, Holger Summer, Falk-Bach Lichtenberger, Cem Erdogan, Maik Gollasch, Stefan Golz, Pontus B. Persson, Johanna Schleifenbaum, Andreas Patzak, Pratik H. Khedkar
Summary: Aging affects the downstream signaling of the endothelial nitric oxide system in vascular smooth muscle, leading to compromised vasorelaxation even in the absence of histopathological alterations. The reduced expression of sGC and PDE5 may contribute to the impaired vasorelaxation in aged vessels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Andreas Friebe, Nils Englert
Summary: NO-GC, a key enzyme in the production of cGMP in the lungs, is primarily found in the cytosol and is activated by nitric oxide and natriuretic peptides. Its precise function in lung tissue, especially in pericytes, remains unclear. However, pharmacological compounds targeting NO-GC have shown promise in treating pulmonary arterial hypertension and may also be useful for asthma, acute respiratory distress syndrome, and pulmonary fibrosis.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Kevin M. Gayler, Jeremy M. Quintana, Jordan Mattke, Michael A. Plunk, Jessica H. Kostyo, Johann W. Karunananthan, Harold Nguyen, Mina Shuda, Liam D. Ferreira, Hannah Baker, Alexandra L. Stinchcomb, Iraida Sharina, Robert R. Kane, Emil Martin
Summary: Previous studies have shown that the anti-hyperlipidemic drug gemfibrozil can activate the NO receptor soluble guanylyl cyclase independently of NO and heme. New gemfibrozil derivatives were synthesized and evaluated for sGC activation, identifying positions in gemfibrozil's structure that are important for activation. Compounds 7c and 15b were found to be more potent activators of purified sGC's cGMP-forming activity compared to gemfibrozil, showing enhanced relaxation of preconstricted mouse thoracic aorta rings. These findings provide insights for further optimization of sGC activators based on the gemfibrozil scaffold.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Maryam Alapa, Chuanlong Cui, Ping Shu, Hong Li, Vlad Kholodovych, Annie Beuve
Summary: The study found that redox modifications play a crucial role in NO activation of GC1, with NO-stimulated GC1 containing more bound Cys, potentially disulfide bonds. Mass spectrometry identified ten oxidized and two reduced Cys in NO-stimulated GC1, and computational modeling narrowed down potential Cys candidates involved in disulfide bonds to Cys489 and Cys571. Mutational studies confirmed the involvement of Cys489 and Cys571 in GC1's response to NO, potentially as a thiol/disulfide switch.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Miguel A. A. Olivencia, Leticia Gil de Biedma-Elduayen, Pablo Gimenez-Gomez, Bianca Barreira, Argentina Fernandez, Javier Angulo, Maria Isabel Colado, Esther O'Shea, Francisco Perez-Vizcaino
Summary: This study investigates the relationship between alcohol abuse and erectile dysfunction (ED), finding that alterations in soluble guanylyl cyclase (sGC) may contribute to ED caused by alcoholism. The results show that alcohol abuse reduces the relaxant response of the corpora cavernosa (CC) but enhances the response to sGC activators, while also increasing reactive oxygen species and protein expression of CYP2E1 and NOX2. These findings suggest that sGC activators may be effective in treating ED associated with alcoholism.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Yue Dai, Emily M. Faul, Arnab Ghosh, Dennis J. Stuehr
Summary: Nitric oxide (NO) signaling in biology relies on its activating cyclic guanosine monophosphate (cGMP) production by the NO receptor soluble guanylyl cyclase (sGC). Physiological levels of NO trigger the mobilization of heme to immature sGC, leading to the construction of functional sGC heterodimers and increased active sGC levels. The process involves glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-heme complexes and the chaperone hsp90.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Nils Englert, Philipp Burkard, Annemarie Aue, Andreas Rosenwald, Bernhard Nieswandt, Andreas Friebe
Summary: NO-GC deletion enhances the fibrotic and inflammatory response in the lungs, indicating the anti-inflammatory and anti-fibrotic properties of NO-GC in pulmonary fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Ayako Tonoki, Saki Nagai, Zhihua Yu, Tong Yue, Sizhe Lyu, Xue Hou, Kotomi Onuki, Kaho Yabana, Hiroki Takahashi, Motoyuki Itoh
Summary: This study identified the gyc beta gene as a negative regulator of age-related memory impairment (AMI) in fruit flies. It was shown that inhibition of the NO-sGC pathway enhanced intermediate-term memory (ITM) in aged individuals, suggesting a potential mechanism underlying memory impairment in aging.
Review
Pharmacology & Pharmacy
Wen Lu, Xiaoxiao Yang, Binghe Wang
Summary: The endogenous signaling roles of carbon monoxide (CO) have been established, but the molecular mechanism of how CO activates soluble guanylyl cyclase (sGC) is not clear. This review examines the discrepancies between the low affinity of sGC for CO and the reported activation, and suggests further studies to improve understanding of the CO-sGC axis.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ellis Nelissen, Melissa Schepers, Laura Ponsaerts, Sebastien Foulquier, Annelies Bronckaers, Tim Vanmierlo, Peter Sandner, Jos Prickaerts
Summary: Vascular cognitive impairment (VCI) is a neurodegenerative disorder characterized by a vascular component, involving decreased cerebral blood flow, white matter lesions, endothelial dysfunction, and blood-brain barrier impairments. Oxidative stress and inflammation are major underlying mechanisms. Modulation of soluble guanylate cyclase (sGC) activity can improve vascular and neural function, and has shown efficacy in cardiovascular diseases.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Physiology
Malte Verheyen, Michelle Puschkarow, Stefanie Gnipp, Doris Koesling, Marcus Peters, Evanthia Mergia
Summary: In this study, we investigated the role of NO-GC isoforms in respiration by measuring lung function parameters of isoform-specific knockout mice. Our findings suggest that NO-GC1-derived cGMP plays a significant role in regulating airway tone, while NO-GC2 affects tissue elasticity and airway reactivity.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Evgeny A. Zemskov, Xiaomin Wu, Saurabh Aggarwal, Mannivannan Yegambaram, Christine Gross, Qing Lu, Hui Wang, Haiyang Tang, Ting Wang, Stephen M. Black
Summary: Our study reveals a novel mechanism regulating PDE3A activity through PKG-Iα-dependent phosphorylation, which is critical for maintaining intracellular cAMP levels and endothelial barrier integrity in the lung. In an animal model of acute lung injury, an increase in PDE3 activity and a decrease in cAMP levels were associated with reduced PKG activity due to nitration of PKG-Iα. Our data suggest a potential therapeutic strategy targeting PKG-Iα to preserve endothelial barrier function in ALI.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Masaya Goto, Shinya Yoshino, Kyona Hiroshima, Toru Kawakami, Kaeko Murota, Shigeru Shimamoto, Yuji Hidaka
Summary: This article reports on the design and preparation of STa analogs for vaccine development and cancer cell detection. It also introduces a convenient chemical method for obtaining STa molecules with the correct conformation.
Review
Biochemistry & Molecular Biology
Gang Wu, Iraida Sharina, Emil Martin
Summary: Nitric oxide (NO), carbon monoxide (CO), oxygen (O-2), and hydrogen sulfide (H2S) are gaseous molecules that play important roles in the physiology and pathophysiology of eukaryotes. Soluble guanylyl cyclase (sGC), a hemoprotein, acts as a sensor and transducer for these gases, as well as a transporter.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Respiratory System
Annemarie Aue, Nils Englert, Leon Harrer, Fabian Schwiering, Annika Gaab, Peter Koenig, Ralf Adams, Achim Schmidtko, Andreas Friebe, Dieter Groneberg
Summary: By utilizing PDGFRβ-tdTomato mice, researchers found that lung pericytes can differentiate into two types of α-SMA expressing myofibroblasts, and the expression of NO-GC decreases during lung fibrosis. This finding reveals the origin and characteristics of myofibroblasts in pulmonary fibrosis.
RESPIRATORY RESEARCH
(2023)
Article
Chemistry, Inorganic & Nuclear
Loyanne C. B. Ramos, Mario Sergio Pereira Marchesi, Daniel Callejon, Marcelo Dias Baruffi, Claure N. Lunardi, Leonardo D. Slep, Lusiane M. Bendhack, Roberto Santana da Silva
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2016)
Article
Materials Science, Biomaterials
Tanira V. Verissimo, Naiara T. Santos, Jaqueline R. Silva, Ricardo B. Azevedo, Anderson J. Gomes, Claure N. Lunardi
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
(2016)
Article
Pharmacology & Pharmacy
Matheus L. Rocha, Bruno R. Silva, Claure N. Lunardi, Leandra N. Z. Ramalho, Lusiane M. Bendhack
VASCULAR PHARMACOLOGY
(2016)
Article
Materials Science, Biomaterials
Claure N. Lunardi, Anderson J. Gomes, Sandeep Palepu, P. Thilanka Galwaduge, Elizabeth M. C. Hillman
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
(2017)
Article
Biochemistry & Molecular Biology
Amanda de Carvalho Pereira, Alice Valenca Araujo, Michele Paulo, Fernanda Aparecida de Andrade, Bruno Rodrigues Silva, Juliana Aparecida Vercesi, Roberto Santana da Silva, Lusiane Maria Bendhack
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2017)
Article
Engineering, Chemical
Fellipy S. Rocha, Anderson J. Gomes, Claure N. Lunardi, Serge Kaliaguine, Gregory S. Patience
CANADIAN JOURNAL OF CHEMICAL ENGINEERING
(2018)
Article
Engineering, Chemical
Anderson J. Gomes, Claure N. Lunardi, Fellipy S. Rocha, Gregory S. Patience
CANADIAN JOURNAL OF CHEMICAL ENGINEERING
(2019)
Article
Biochemistry & Molecular Biology
Alice V. Araujo, Fernanda A. Andrade, Michele Paulo, Tiago D. de Paula, Simone R. Potje, Amanda C. Pereira, Lusiane M. Bendhack
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2019)
Article
Engineering, Environmental
Anderson J. Gomes, Odair A. Barbizan, Caroline C. Lessa, Tatiana A. Campos, Herick S. Muller, Vicente P. Martins, Claure N. Lunardi
JOURNAL OF POLYMERS AND THE ENVIRONMENT
(2019)
Article
Materials Science, Multidisciplinary
Fellipy S. Rocha, Anderson J. Gomes, Claure N. Lunardi
MATERIALS RESEARCH BULLETIN
(2019)
Review
Pharmacology & Pharmacy
Michele Paulo, Daniela E. F. R. Costa, Daniella Bonaventura, Claure N. Lunardi, Lusiane M. Bendhack
CURRENT PHARMACEUTICAL DESIGN
(2020)
Review
Engineering, Chemical
Claure N. Lunardi, Anderson J. Gomes, Fellipy S. Rocha, Jacopo De Tommaso, Gregory S. Patience
Summary: Zeta potential is a parameter expressing electrochemical equilibrium between particles and liquids, with applications in various fields. Proper characterization of nanoparticles, including information on size, surface charge, stability, and agglomeration behavior, is essential for developing therapeutic nanoformulations. Challenges in this approach include inadequate knowledge of standards, data interpretation, and laboratory practices.
CANADIAN JOURNAL OF CHEMICAL ENGINEERING
(2021)
Article
Multidisciplinary Sciences
Marina Lima Rodrigues, Anderson de Jesus Gomes, Mani Indiana Funez, Mariane Aparecida da Silva Marques, Claure Nain Lunardi
Summary: The encapsulation of drugs in micro and nanocarriers helps to reduce drug side effects and preserve their desired properties. In this study, PLGA was used to encapsulate E-latex and its properties were evaluated using spectrophotometric techniques. The results showed that E-NPs exhibited antinociceptive effects, confirming their potential as stable drug delivery devices.
Article
Chemistry, Medicinal
Claure Nain Lunardi, Fernanda Lima Subrinho, Mirella Paula de Freitas Barros, Raiane Cavalcante Lima, Ana Clara Magalhaes de Queiroz Melo, Daniela de Melo Barbosa, Luana Gouveia De Negreiros, Brenda Soares Rodrigues, Mateus Sousa Neiva, Joao Victor Ribeiro Linhares, Gabriel Farrapeira Dalla Costa, Anderson de Jesus Gomes
Summary: This study provides a comprehensive understanding of the relationship between COVID-19 and nanotechnology through bibliometric analysis, offering theoretical basis and research directions for further studies.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Claure N. Lunardi, Mirella P. F. Barros, Marina L. Rodrigues, Anderson J. Gomes
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)
