Article
Biochemistry & Molecular Biology
Paul Tawa, Lei Zhang, Essam Metwally, Yan Hou, Mark A. McCoy, W. Michael Seganish, Rumin Zhang, Emily Frank, Payal Sheth, Jennifer Hanisak, Christopher Sondey, David Bauman, Aileen Soriano
Summary: cGMP-dependent protein kinase (PKG) is an important drug target for cardiovascular diseases. In this study, a novel series of activators were identified that can directly bind and enhance the kinase activity of PKG1. These activators mimic the effect of cGMP on PKG1 by modulating its kinetic parameters and binding affinity for cGMP. They act by binding to an allosteric site near the regulatory domain of PKG1.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Chad D. Schwartzkopf, John R. Hadcock, Guang Liu, Peter Germano, Julien Roux, Courtney M. Shea, Emmanuel S. Buys, Juli E. Jones
Summary: Praliciguat treatment showed metabolic effects of increasing energy utilization, improving insulin sensitivity, and reducing plasma triglycerides in diet-induced obesity (DIO) mice.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Alexandra Petraina, Cristian Nogales, Thomas Krahn, Hermann Mucke, Thomas F. Luscher, Rodolphe Fischmeister, David A. Kass, John C. Burnett, Adrian J. Hobbs, Harald H. H. W. Schmidt
Summary: Mechanism-based therapy focused on understanding disease pathways at the molecular level is still rare in cardiovascular medicine, but recent drug developments centered around cGMP offer promising personalized treatment options. By modulating cGMP synthesis or breakdown, these drugs show potential for protective effects across various cardiac conditions.
CARDIOVASCULAR RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Erika L. Poitras, Stephen L. Gust, Paul M. Kerr, Frances Plane
Summary: Nitric oxide activates enzyme soluble guanylate cyclase to produce cGMP, which plays a key role in regulating intracellular calcium levels. PDE5 inhibitors like sildenafil prolong cGMP availability, making them first-line treatments for erectile dysfunction and approved for pulmonary arterial hypertension. Inhaled NO is currently used for neonatal persistent pulmonary hypertension, but alternative approaches are needed for unresponsive cases.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Plant Sciences
Davoud Ahmadimoghaddam, Mohammad Zarei, Saeed Mohammadi, Zohreh Izadidastenaei, Iraj Salehi
Summary: In Iranian folkloric medicine, Bupleurum falcatum L. has been used as a selective analgesic remedy. The research investigated the anti-nociceptive and anti-allodynic action of Bupleurum falcatum L. roots essential oil in Swiss mice. Results showed that BFEO exhibited significant antinociceptive effects and could effectively alleviate allodynia in CSC mice by activating specific pathways and receptors.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Noriyoshi Ogino, Hidekazu Takahashi, Kenjiro Nagaoka, Yuki Harada, Masayuki Kubo, Koichiro Miyagawa, Masashi Kusanaga, Shinji Oe, Yuichi Honma, Masaru Harada, Masamitsu Eitoku, Narufumi Suganuma, Keiki Ogino
Summary: The study found that the increase in arginase activity in the plasma of obese mice is positively correlated with blood glucose levels, along with an increase in exosomal arginase-1 levels. The liver of high-fat diet-fed mice showed a significant increase in arginase-1 expression, and exposure to high glucose increased the expression of arginase-1 in exosomes and total lysates of HepG2 cells.
Article
Pharmacology & Pharmacy
Bozena Badzynska, Ivana Vaneckova, Janusz Sadowski, Silvie Hojna, Elzbieta Kompanowska-Jezierska
Summary: This study investigated the effects of ETA and ETB receptor blockade on blood pressure, medullary blood flow, and tissue NO in different rat models. The results confirmed the dominant role of ETA receptors in regulating blood pressure and renal hemodynamics in both normotensive and hypertensive rats. Additionally, ETB stimulation was found to preserve medullary perfusion under conditions of endothelin system activation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biology
Lukas Menges, Jan Giesen, Kerem Yilmaz, Evanthia Mergia, Annette Fuechtbauer, Ernst-Martin Fuechtbauer, Doris Koesling, Michael Russwurm
Summary: The presence of NO/cGMP signaling in cardiac cells is still disputed. Recent experiments have shown that NO can induce cGMP signals in cardiac fibroblasts, but not in cardiomyocytes. However, in a co-culture model, cGMP produced in fibroblasts in response to NO can enter cardiomyocytes through gap junctions. In intact tissue, we demonstrate that cGMP produced in cardiac fibroblasts can be transferred to cardiomyocytes via gap junctions.
COMMUNICATIONS BIOLOGY
(2023)
Review
Plant Sciences
Jeremy Astier, Jordan Rossi, Pauline Chatelain, Agnes Klinguer, Angelique Besson-Bard, Claire Rosnoblet, Sylvain Jeandroz, Valerie Nicolas-Frances, David Wendehenne
Summary: The study of nitric oxide in embryophytes and algae has deepened our understanding of its biological functions, including its production pathways, signaling networks, and regulated proteins. Interestingly, while some algae have a conserved nitric oxide synthase, the typical NO-cyclic GMP signaling module is not found in algae or embryophytes, showing a divergent acquisition of NO signaling between green and animal lineages.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Multidisciplinary Sciences
Maximilian W. Schenk, Sam Humphrey, A. S. Md Mukarram Hossain, Mitchell Revill, Sarah Pearsall, Alice Lallo, Stewart Brown, Samuel Bratt, Melanie Galvin, Tine Descamps, Cong Zhou, Simon P. Pearce, Lynsey Priest, Michelle Greenhalgh, Anshuman Chaturvedi, Alastair Kerr, Fiona Blackhall, Caroline Dive, Kristopher K. Frese
Summary: In small cell lung cancer, acquired resistance to standard platinum-etoposide chemotherapy often occurs, with Notch and nitric oxide pathways playing a role in mediating this resistance. Upregulation of soluble guanylate cyclase in residual tumor cells is associated with chemoresistance, highlighting this pathway as a potential target for treating relapsed SCLC.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Victor W. Mak, Akash M. Patel, Rose Yen, Jennifer Hanisak, Yeon-Hee Lim, Jianming Bao, Rong Zheng, W. Michael Seganish, Yang Yu, David R. Healy, Aimie Ogawa, Zhao Ren, Aileen Soriano, Grigori P. Ermakov, Maribel Beaumont, Essam Metwally, Alan C. Cheng, Andreas Verras, Thierry Fischmann, Matthias Zebisch, H. Leonardo Silvestre, Paul A. McEwan, John Barker, Paul Rearden, Thomas J. Greshock
Summary: Activation of PKG1 alpha is a promising approach for treating cardiovascular diseases, as it induces various beneficial effects such as smooth muscle relaxation and prevention of platelet aggregation. In this study, small molecule activators were optimized and shown to have anti-proliferative effects in human pulmonary arterial smooth muscle cells. Mechanistic studies revealed that the activators work through a similar mechanism as cGMP and bind to an allosteric pocket in close proximity to the cyclic nucleotide-binding domain.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Ravneet Singh, Victoria L. Nasci, Ginger Guthrie, Lale A. Ertuglu, Maryam K. Butt, Annet Kirabo, Eman Y. Gohar
Summary: Cardiovascular and renal diseases are increasingly prevalent and age and sex differences play a role in their development and progression. GPER1 has been identified as an important regulator in cardio-renal health, particularly in aging individuals.
Review
Pediatrics
Simonetta Genovesi, Marco Giussani, Antonina Orlando, Giulia Lieti, Francesca Viazzi, Gianfranco Parati
Summary: The mechanisms regulating blood pressure are complex, with the balance between endothelin-1 and nitric oxide playing a crucial role. While increased endothelin-1 activity and decreased nitric oxide bioavailability are commonly observed in hypertensive adults, there is less clarity in children and adolescents. The role of obesity in stimulating endothelin-1 production and the potential overproduction of nitric oxide in younger obese and hypertensive individuals add further complexity to the understanding of hypertension development in this population.
PEDIATRIC NEPHROLOGY
(2022)
Review
Endocrinology & Metabolism
Linda S. Gutierrez, Jovita Gutierrez
Summary: The thrombospondin family consists of five glycoproteins that play regulatory roles in cell migration and activation of latent transforming growth factors, impacting immune processes. Recent studies show associations between TSP1 and metabolic disorders like obesity, diabetes, and cardiovascular diseases, highlighting its potential as a therapeutic target for metabolic diseases.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Pharmacology & Pharmacy
Carmem Peres Valgas da Silva, Fabiano Calmasini, Eduardo Costa Alexandre, Helena Fonseca Raposo, Maria Andreia Delbin, Fabiola Zakia Monica, Angelina Zanesco
Summary: The study showed that mirabegron treatment significantly increased energy expenditure in obese mice, improved obesity symptoms, and reduced circulating levels of free fatty acids, glycerol, insulin, inflammatory factors, etc. Additionally, mirabegron may also reverse lipid deposits in the liver and brown adipose tissue.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2021)
Review
Nutrition & Dietetics
F. B. Calmasini, F. H. Silva, E. C. Alexandre, E. Antunes
Summary: Resveratrol, a polyphenol found naturally in fruits and plants, has shown beneficial properties in improving metabolic and lipid profiles, as well as antioxidant, anti-inflammatory and anti-proliferative effects. In studies involving the urogenital tract, resveratrol has been tested as a therapeutic drug in various diseases, particularly lower urinary tract symptoms, non-cancerous prostatic disease, and erectile dysfunction. In vitro studies have shown that resveratrol reduces inflammation and oxidative stress, and improves endothelial function in UGT. Despite its low oral bioavailability, in vivo administration of resveratrol has been proven effective in improving UGT-related dysfunctions in animal models. However, there is still insufficient clinical evidence to establish its efficacy in human UGT-related diseases. Future clinical trials are necessary to further investigate the potential of resveratrol as a treatment option.
NUTRITION RESEARCH REVIEWS
(2023)
Article
Multidisciplinary Sciences
Andressa Kely Pinheiro, Dalila Andrade Pereira, Jean Leandro dos Santos, Fabiano Beraldi Calmasini, Eduardo Costa Alexandre, Leonardo Oliveira Reis, Arthur L. Burnett, Fernando Ferreira Costa, Fabio Henrique Silva
Summary: This study evaluated the effects of a hybrid compound RVT-FxMe on two murine models displaying priapism phenotype. The results showed that RVT-FxMe reversed the enhanced NO-cGMP-mediated corpus cavernosum relaxations in eNOS(-/-) mice, but not in SCD mice. The excess of plasma hemoglobin in SCD mice may interfere in the pharmacological activity of NO donors compounds.
Article
Biochemistry & Molecular Biology
Ana Paula Magrini Iacopucci, Pamela da Silva Pereira, Dalila Andrade Pereira, Fabiano Beraldi Calmasini, Valeria Pittala, Leonardo Oliveira Reis, Arthur L. Burnett, Fernando Ferreira Costa, Fabio Henrique Silva
Summary: In this study, a mouse model was used to investigate the effect of intravascular hemolysis on corpus cavernosum smooth muscle relaxation and oxidative stress in the penis. The results showed that intravascular hemolysis promotes increased corpus cavernosum smooth muscle relaxation, accompanied by upregulation of HO-1 expression and oxidative stress. This study provides support for clinical studies that have shown a strong positive correlation between priapism and high levels of intravascular hemolysis in men with SCD.
Article
Physiology
Pamela da Silva Pereira, Dalila Andrade Pereira, Fabiano Beraldi Calmasini, Leonardo O. Reis, Nathan Brinkman, Arthur L. Burnett, Fernando Ferreira Costa, Fabio Henrique Silva
Summary: This study found that in sickle cell disease, decreased haptoglobin levels contribute to abnormal erectile function. Treatment with haptoglobin can improve erectile function by regulating the expression of key proteins involved in the control of penile erection. This suggests that haptoglobin treatment may be an additional strategy to prevent priapism in sickle cell disease.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Oncology
Anita Cassoli Cortez, Marcia Torresan Delamain, Leandro Luiz Lopes de Freitas, Andre Almeida Schenka, Fabiano Reis
HEMATOLOGY TRANSFUSION AND CELL THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Antonio Tiago Lima, Eric Xavier dos Santos, Jose Britto-Junior, Valeria B. de Souza, Andre A. Schenka, Rafael Campos, Manoel Odorico Moraes, Maria Elisabete A. Moraes, Edson Antunes, Gilberto De Nucci
Summary: 6-Nitrodopamine (6-ND) is a newly released catecholamine that can cause powerful vasorelaxation by acting as a potent and selective dopamine D2-like receptor antagonist. Its synthesis/release can be inhibited by nitric oxide (NO) synthase inhibitor or by removal of the endothelium.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Jose Marcos Vieira Rocha, Valeria Barbosa de Souza, Patricia Costa Panunto, Jacqueline Spacagna Nicolosi, Emanueli do Nascimento da Silva, Solange Cadore, Oscar Moscoso Londono, Diego Muraca, Pablo Tancredi, Marina de Brot, Wilson Nadruz, Ana Lucia Tasca Gois Ruiz, Marcelo Knobel, Andre Almeida Schenka
Summary: This study synthesized citrate-coated iron oxide nanoparticles and evaluated their potential toxic effects using in vitro and in vivo models. The results showed that these nanoparticles had no adverse effects on cell viability and vital organ morphology. Therefore, this study provides a simple, fast, and reproducible method for the development of a safe drug nanodelivery system.
Article
Andrology
Gabriela Reolon Passos, Guilherme Ruiz Leonardi, Mariana Goncalves de Oliveira, Erick de Toledo Gomes, Ana Carolina Ghezzi, Edson Antunes, Fernanda Andrade Orsi, Jose Luiz da Costa, Fabiola Zakia Monica
Summary: This study aimed to assess the effects of serum obtained from unvaccinated men with severe COVID-19 on isolated corpus cavernosum (CC) from mice. The results showed that the relaxation responses in CC incubated with COVID-19 serum were significantly reduced compared to the control serum. However, the relaxation induced by a specific activator was unaffected in CC stimulated with the COVID-19 serum. In addition, COVID-19 serum increased the expression of specific genes. These findings suggest that COVID-19 may lead to erectile dysfunction.
Article
Biochemistry & Molecular Biology
Matheus L. Medeiros, Akila L. Oliveira, Glaucia C. Mello, Edson Antunes
Summary: Exposure to methylglyoxal (MGO) increases inflammatory responses in mouse airways, but the use of metformin can reduce these effects. In this study, mice exposed to MGO showed increased levels of inflammatory cells and cytokines, as well as mucus production and collagen deposition. However, treatment with metformin reversed these effects and suppressed the activation of RAGE-ROS signaling. These findings suggest that metformin may be a potential adjuvant therapy for asthma in individuals with high MGO levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Jose Britto-Junior, Lincoln Rangel Medeiros-Teixeira, Antonio Tiago Lima, Leticia Costa Dassow, Rodrigo alvaro Brandao Lopes-Martins, Rafael Campos, Manoel Odorico Moraes, Maria Elisabete A. Moraes, Edson Antunes, Gilberto De Nucci
Summary: The study found that 6-nitrodopamine is the major catecholamine released from rat isolated ventricles and is 1000 times more potent than dopamine and noradrenaline in increasing heart inotropism. It is selectively blocked by atenolol.
Article
Biology
J. Britto-Junior, A. T. Lima, J. S. Santos-Xavier, P. Gonzalez, F. Z. Monica, R. Campos, V. B. de Souza, A. A. Schenka, E. Antunes, G. De Nucci
Summary: This study investigated the release of 6-nitrodopamine in the thoracic aorta and pulmonary artery rings of marmosets. The results showed that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues. It acts as a potent and selective antagonist of dopamine D2-like receptors and induces vasodilation by releasing NO.
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Dalila Andrade Pereira, Danillo Andrade Pereira, Pamela da Silva Pereira, Tammyris Helena Rebecchi Silveira, Fabiano Beraldi Calmasini, Leonardo Oliveira Reis, Fernando Ferreira Costa, Fabio Henrique Silva
Summary: Hydroxyurea treatment is not effective for priapism associated with sickle cell disease (SCD). Excess plasma hemoglobin and reactive oxygen species in SCD may react with nitric oxide (NO) before it binds to guanylyl cyclases (GCs) in the smooth muscle of the corpus cavernosum, preventing the restoration of baseline NO/cGMP levels. Furthermore, downregulation of endothelial NO synthase in the penis may impair the pharmacological action of hydroxyurea at the endothelial level in SCD mice. Therefore, alternative therapeutic approaches for priapism in SCD that are not hindered by high plasma hemoglobin and reactive oxygen species levels need to be explored.
Article
Physiology
Akila L. Oliveira, Matheus L. Medeiros, Ana Carolina Ghezzi, Gabriel Alonso dos Santos, Glaucia Coelho Mello, Fabiola Z. Monica, Edson Antunes
Summary: High levels of MGO and AGEs, along with activation of the RAGE pathway, contribute to diabetes-associated bladder dysfunction. Treatment with the AGE breaker ALT-711 can reduce MGO levels and improve bladder function in diabetic mice.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Biology
A. P. Jarrete, L. T. Giollo-Junior, J. F. Vilela-Martin, I. P. Novais, M. A. Delbin, A. Zanesco
Summary: This study found that postmenopausal women (PMW) with type 2 diabetes mellitus (T2DM) have a higher risk of cardiovascular complications compared to diabetic men. Diabetic PMW showed impaired microvascular function, higher levels of pro-inflammatory biomarkers (CML and CRP), and lower adiponectin concentration. This suggests that diabetic PMW are more susceptible to the detrimental effects of hyperglycemia compared to men.
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2022)