Article
Cardiac & Cardiovascular Systems
Jie Su, Pierre Coleman, Angeliki Ntorla, Rhys Anderson, Michael J. Shattock, Joseph R. Burgoyne
Summary: This study demonstrates that the cytosolic DNA sensor cGAS can activate PKGI directly through the generation of cGAMP, showing a link between inflammation and blood pressure regulation.
Article
Biochemistry & Molecular Biology
Avelina Lee, Iryna Lebedyeva, Wenbo Zhi, Vani Senthil, Herjot Cheema, Michael W. Brands, Weston Bush, Nevin A. Lambert, Madeline Snipes, Darren D. Browning
Summary: Phosphodiesterase-5 inhibitors (PDE5i) are being studied for their potential in preventing colon cancer. However, their side-effects and interactions with other drugs have been a concern. By modifying the prototypical PDE5i sildenafil, we developed a new analog called malonyl-sildenafil which exhibited reduced lipophilicity and showed promising effects on colon epithelium. This analog suppressed proliferation in the colon epithelium, providing a novel approach to developing a first-in-class drug for colon cancer chemoprevention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Applied
Oswaldo Perez, Nicolaas Schipper, Martin Bollmark
Summary: The synthesis of the cyclic guanosine monophosphorothioate analogue 1a was achieved through a diastereoselective route, utilizing a silyl protection sequence to achieve high selectivity for the desired product. This chromatography-free process allowed for a successful scale-up production of the compound.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Microbiology
Ruizhen Li, Wenli Liu, Xiangrui Yin, Fangfang Zheng, Zhenyu Wang, Xingchen Wu, Xiaohua Zhang, Qian Du, Yong Huang, Dewen Tong
Summary: This study found that Brucella outer membrane protein Omp25 could suppress the production of IFN-beta and its downstream IFN-stimulated genes induced by various DNA viruses or IFN-stimulatory DNA. Omp25 promoted the degradation of cyclic GMP-AMP synthase (cGAS) via the ubiquitin-proteasome-dependent pathway, leading to the inhibition of IFN-beta induction in various mammalian monocyte/macrophages.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Cell Biology
Zhilei Wang, Nian Chen, Zhiyong Li, Guang Xu, Xiaoyan Zhan, Jianyuan Tang, Xiaohe Xiao, Zhaofang Bai
Summary: Inflammation is a protective response regulated by the host, with cGAS-STING pathway playing a crucial role in immune defense, viral infections, fatty liver, and cancer metastasis. The potential impact of this pathway in liver diseases has attracted widespread attention, with pharmacological agonists and antagonists offering new therapeutic possibilities. Understanding the mechanisms of cGAS-STING pathway may lead to the development of effective treatments for liver diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Guangshuo Zhu, Kazutaka Ueda, Masaki Hashimoto, Manling Zhang, Masayuki Sasaki, Taro Kariya, Hideyuki Sasaki, Nina Kaludercic, Dong-Ik Lee, Djahida Bedja, Matthew Gabrielson, Yuan Yuan, Nazareno Paolocci, Robert M. Blanton, Richard H. Karas, Michael E. Mendelsohn, Brian O'Rourke, David A. Kass, Eiki Takimoto
Summary: This study found that PDE5i improves heart failure by activating the PKG-PGC1 alpha axis, which enhances mitochondrial respiration and upregulates PGC1 alpha mRNA. However, the cardioprotective effects of PDE5i were abolished in hearts lacking the PGC1 alpha gene.
Article
Cardiac & Cardiovascular Systems
Qingtong Wang, Ying Wang, Toni M. West, Yongming Liu, Gopireddy R. Reddy, Federica Barbagallo, Bing Xu, Qian Shi, Bingqing Deng, Wei Wei, Yang K. Xiang
Summary: By studying the molecular signaling and positive cardiac contractility induced by beta-blockers in the heart, it was found that carvedilol can promote cardiac inotropy and have a protective effect in diabetic mice. The observations suggest a novel beta(1)AR-NOS3 signaling pathway that may be targeted in therapy for heart diseases with reduced ejection fraction.
CARDIOVASCULAR RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Qingtong Wang, Ying Wang, Toni M. West, Yongming Liu, Gopireddy R. Reddy, Federica Barbagallo, Bing Xu, Qian Shi, Bingqing Deng, Wei Wei, Yang K. Xiang
Summary: The study investigated the molecular signaling and effects of beta-blockers on cardiac inotropy in animal hearts. The results showed that carvedilol, a beta-blocker, can promote cardiac contractility through a specific signaling pathway, restoring heart function in diabetic mice and reducing cell apoptosis and hypertrophy in diabetic hearts.
CARDIOVASCULAR RESEARCH
(2021)
Article
Multidisciplinary Sciences
Laurence M. Occelli, Kelian Sun, Paige A. Winkler, Brandy J. Morgan, Simon M. Petersen-Jones
Summary: The purpose of this study was to investigate whether raised levels of retinal cyclic guanosine monophosphate (cGMP) in PDE6A(-/-) dogs was reflected in plasma levels. The results showed that cGMP levels were significantly elevated in retinal samples of 2-month-old PDE6A(-/-) dogs, but there was no significant difference in plasma cGMP levels. Therefore, plasma cGMP levels may not be a useful biomarker for the disease at the 2-month timepoint.
Article
Medicine, General & Internal
Keshab Kumar Karna, Bo-Ram Choi, Chul-Young Kim, Hye-Kyung Kim, Jong-Kwan Park
Summary: This study found that Rubus occidentalis and ellagic acid can induce relaxation of rabbit penile corpus cavernosum smooth muscle by activating the nitric oxide signaling pathway, which may improve erectile function.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Jong Seong Roh, Hoim Jeong, Beomgu Lee, Byung Wook Song, Seung Jin Han, Dong Hyun Sohn, Seung-Geun Lee
Summary: The study revealed that mirodenafil has the potential to alleviate skin fibrosis caused by SSc by downregulating the TGF-β/Smad signaling pathway.
ANIMAL CELLS AND SYSTEMS
(2021)
Article
Medicine, General & Internal
Carla Sala, Marta Rescaldani, Elisa Gherbesi, Gianni Bolla, Cesare Cuspidi, Massimiliano Ruscica, Stefano Carugo
Summary: The present study found that chronic aldosterone excess impairs the platelet nitric oxide/cGMP pathway in humans, possibly due to potassium depletion caused by aldosterone.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Microbiology
Myles B. Poulin, Laura L. Kuperman
Summary: Bacterial biofilms provide advantages such as adherence, immune evasion, and antibiotic resistance, contributing to a majority of human infections. The signaling molecule c-di-GMP plays a crucial role in the biosynthesis and export of biofilm exopolysaccharides, and targeting this molecule shows promise in treating antibiotic-resistant and biofilm-forming bacteria.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Nicola J. A. Scott, Timothy C. R. Prickett, Christopher J. Charles, Christopher M. Frampton, A. Mark Richards, Miriam T. Rademaker
Summary: This study demonstrates for the first time that combined PDE9 inhibition and NEP inhibition has additional beneficial hemodynamic and renal effects in heart failure. This dual enhancement of NP bioactivity supports PI+NI as a potential therapeutic strategy for heart failure.
JACC-HEART FAILURE
(2023)
Article
Pharmacology & Pharmacy
Behnam Ghorbanzadeh, Mohammad Amin Behmanesh, Roya Mahmoudinejad, Mehdi Zamaniyan, Shadi Ekhtiar, Yousef Paridar
Summary: In this study, researchers found that the leukotriene receptor antagonist, montelukast, reduced colonic tissue damage induced by acetic acid and decreased inflammatory levels. The study also revealed that the NO-cGMP-KATP channel pathway is involved in the protective effect of montelukast.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Leonardo M. Fabri, Malson N. Lucena, Daniela P. Garcon, Cintya M. Moraes, John C. McNamara, Francisco A. Leone
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
(2019)
Article
Environmental Sciences
M. Capparelli, J. C. McNamara, M. G. Grosell
BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
(2020)
Article
Physiology
Samuel Coelho Faria, Adalto Bianchini, Mariana Machado Lauer, Ana Lucia Ribeiro Latorre Zimbardi, Federico Tapella, Maria Carolina Romero, John Campbell McNamara
FRONTIERS IN PHYSIOLOGY
(2020)
Article
Environmental Sciences
M. V. Capparelli, J. C. McNamara, G. S. Araujo, A. C. F. Cruz, D. M. S. Abessa
Summary: The study compared sediment quality in estuaries at three locations along the coast of Sao Paulo State, Brazil, during two seasons of 2013. Results showed that sediments from the most protected locality had lower metal pollution and toxicity compared to those from less protected areas, which exhibited signs of environmental degradation.
BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francisco A. Leone, Malson N. Lucena, Leonardo M. Fabri, Daniela P. Garcon, Carlos F. L. Fontes, Rogerio O. Faleiros, Cintya M. Moraes, John C. McNamara
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
(2020)
Article
Biology
Milene Mantovani, John Campbell McNamara
Summary: The study revealed that the freshwater crab Pagei survives in fresh water by maintaining cellular isosmoticity, while the shrimp Jelskii exhibits clear hypo-osmoregulatory ability. Each of the two species has evolved distinct transcriptional and systemic strategies to adapt to the freshwater environment.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2021)
Article
Marine & Freshwater Biology
Mariana V. Capparelli, Carl L. Thurman, Paloma Gusso Choueri, Denis Moledo de Souza Abessa, Mayana Karoline Fontes, Caio Rodrigues Nobre, John Campbell McNamara
Summary: This study compared the physiological and biochemical adjustments of two fiddler crab species from the Galapagos archipelago to submersion and desiccation challenges, revealing species-specific survival and stress responses. The integrated biomarker response index based on oxidative stress indicated higher oxidative stress in Leptuca helleri, while submersion had a greater impact on Minuca galapagensis.
Article
Marine & Freshwater Biology
Daniela P. Garcon, Francisco A. Leone, Rogerio O. Faleiros, Marcelo R. Pinto, Cintya M. Moraes, Leonardo M. Fabri, Claudia D. Antunes, John Campbell McNamara
Summary: Salt tolerance in Brachyura is closely related to their ability to adjust body fluid concentrations, with mechanisms relying on the gill (Na+, K+)-ATPase. Callinectes danae demonstrates intricate osmotic and chloride regulation abilities under different salinity conditions, which are linked to variations in ATPase activity, protein expression, and mRNA expression.
Article
Biochemistry & Molecular Biology
Anieli Cristina Maraschi, Samuel Coelho Faria, John Campbell McNamara
Summary: This study focused on the ion regulation capabilities of palaemonid shrimps in different salinity environments. Palaemonids exhibit hypo-regulation in high salinity and hyper-regulation in low salinity. The research revealed a positive correlation between the expression of gill NKCC protein and the hemolymph's hyper-osmoregulatory capacity, suggesting a role for NKCC in salt secretion.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
(2021)
Article
Environmental Sciences
Mariana V. Capparelli, John C. McNamara, Carl L. Thurman, Rosela Perez-Ceballos, Mario A. Gomez-Ponce, Jose-Gilberto Cardoso-Mohedano, Gabriel M. Moulatlet
Summary: We assessed the responses of mangrove crabs to global climate changes and found that more terrestrial species were better adapted to survive in water, while less terrestrial species were more adapted to live on land.
MARINE POLLUTION BULLETIN
(2022)
Article
Zoology
John Campbell McNamara, Carolina Arruda Freire
Summary: Early marine invertebrates adapted to dilute media by acquiring osmoregulatory abilities. These adaptations include reduced body permeability, lowered osmotic concentrations, and increased osmotic gradients. Assessing freshwater invertebrates that have successfully invaded this environment, we find diverse osmoregulatory characteristics influenced by body plans, morpho-physiological resources, and occupation routes.
INTEGRATIVE AND COMPARATIVE BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Leonardo M. Fabri, Cintya M. Moraes, Maria I. C. Costa, Daniela P. Garcon, Carlos F. L. Fontes, Marcelo R. Pinto, John C. McNamara, Francisco A. Leone
Summary: This study investigated the regulation of gill (Na+, K+)-ATPase activity in freshwater crustaceans, finding that protein kinases A and C, as well as FXYD2 peptide, play a role in modulating enzyme activity through phosphorylation mechanisms instead of through the expression of different isoforms.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Zoology
Samuel Coelho Faria, John Campbell McNamara
Summary: Weakly osmoregulating crustaceans use intracellular free amino acids (FAA) to attenuate cell volume changes, but it is unknown if semiterrestrial, strong hyper/hypo-osmoregulators have this ability. This study investigates FAA mobilization in muscle tissue of 10 fiddler crabs from different genera along the Atlantic coast of South America. The results show that hypo-osmoregulating crabs can mobilize FAA, likely due to a lesser ability to secrete salt near their upper critical limits. On the other hand, hyper-osmoregulating crabs have a strong extracellular regulatory ability, so FAA plays a diminished role in isosmotic intracellular regulation.
JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY
(2023)
Article
Biology
John Campbell McNamara, Anieli Cristina Maraschi, Federico Tapella, Maria Carolina Romero
Summary: This study examines the osmoregulatory characteristics and gene expression of two sub-Antarctic Eubrachyura crabs in low temperature environments. The results show that while both crabs exhibit similar systemic osmoregulatory characteristics, their gene expression for ion uptake and secretion differs significantly.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2023)
Meeting Abstract
Zoology
J. C. McNamara, C. A. Freire
INTEGRATIVE AND COMPARATIVE BIOLOGY
(2023)