Article
Veterinary Sciences
Alessandro Di Cerbo, Luca Roncati, Carlotta Marini, Gianluca Carnevale, Manuela Zavatti, Rossella Avallone, Lorenzo Corsi
Summary: The study found that DHEA exerts neuroprotective effects in an animal model of HE, improving locomotor activity by modulating PKCε expression. Additionally, the expression of PKCε in the cortex and cerebellum is regulated by NH4Cl and DHEA.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Ellis Nelissen, Elentina K. Argyrousi, Nick P. Van Goethem, Fuqiang Zhao, Catherine D. G. Hines, Gayathri Swaminath, Michael Gerisch, Joerg Hueser, Peter Sandner, Jos Prickaerts
Summary: The study found that the sGC stimulator vericiguat can enhance long-term memory by increasing hippocampal plasticity and promoting the translocation of oc-AMPA receptors to the cell membrane, while having no effect on blood pressure and cerebral blood volume. Stimulation of sGC may provide a new therapeutic strategy for treating VCI.
Article
Gastroenterology & Hepatology
Wu Yang, Hao He, Tongtong Wang, Nan Su, Feng Zhang, Kai Jiang, Jing Zhu, Chonghe Zhang, Kongyan Niu, Luyue Wang, Xiaodong Yuan, Nan Liu, Lingjie Li, Wu Wei, Junhao Hu
Summary: The study found that in liver fibrosis, HSCs undergo significant transcriptomic changes rather than PFs, and HSCs are the exclusive source of myofibroblasts in CCL4-treated livers, while PFs are the major source in early cholestatic liver fibrosis. Single-cell RNA sequencing and lineage-tracing analysis uncovered differential gene-expression features between HSCs and PFs, providing evidence that these differences should be considered in developing antifibrotic therapeutic strategies.
Article
Cardiac & Cardiovascular Systems
Wahiba Dhahri, Sylvie Dussault, Nozha Raguema, Michel Desjarlais, Alain Rivard
Summary: This study found that Riociguat, an sGC stimulator, promotes angiogenesis and improves neovascularization after ischemia. The mechanism involves the activation of the p44/p42 MAP kinase pathway and an increase in the number and functions of PACs. This discovery could potentially serve as a new therapeutic strategy for reducing tissue ischemia in patients with severe atherosclerotic diseases.
Article
Biochemistry & Molecular Biology
Sahar Aminzai, Tingfei Hu, Renate B. Pilz, Darren E. Casteel
Summary: This study found that purified PKGI alpha can be oxidized and activated during storage, indicating that oxidation and trace metals present during storage play a role in PKGI alpha activation. Previous research suggested that certain amino acids in PKGI alpha are key for oxidation-induced activation. However, there is currently no direct evidence of oxidation-induced PKGI alpha activation in vivo.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Archana Arjunan, Dhiraj Kumar Sah, Young Do Jung, Juhyun Song
Summary: Hepatic encephalopathy is a severe metabolic syndrome associated with liver disorders, with limited treatment options available. The disease is a neuropsychiatric complication linked with cognitive decline, coma, and death, and its pathogenesis remains unclear. Melatonin, as the sole endogenous hormone related to HE, has neuroprotective effects by crossing the blood-brain barrier.
Review
Multidisciplinary Sciences
Se-Min Kim, Tony Yuen, Jameel Iqbal, Mishaela R. Rubin, Mone Zaidi
Summary: The NO-cGMP-PKG pathway is crucial for skeletal homeostasis, but long-term use of NO is limited by off-target effects. Inhibiting cGMP-specific phosphodiesterase to promote the anabolic signal offers a potential treatment for osteoporosis with PDE5A inhibitors. Further research is needed to investigate the specific effects of PDE5A inhibition on bone cells and the pathophysiological changes in skeletal PDE5A expression.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Hongcheng Jiang, Yue Jiang, Yunkun Qu, Jiagao Lv, Hesong Zeng
Summary: This study aimed to investigate whether and how the sGC-PRKG1 signaling pathway promotes the formation of thoracic aortic dissection (TAD). The researchers identified two modules highly relevant to TAD and focused on the involvement of endothelial NOS (eNOS) in TAD progression. The results showed that the sGC-PRKG1 signaling pathway promotes TAD formation by inducing vascular smooth muscle cells (VSMCs) phenotype transition, which was confirmed through various experiments. Overall, this study reveals the importance of the sGC-PRKG1 signaling pathway in TAD development.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Plant Sciences
Liqian Chen, Xinghong Zhou, Yijian Deng, Ying Yang, Xiaohu Chen, Qinghong Chen, Yanyan Liu, Xiuqiong Fu, Hiu Yee Kwan, Yanting You, Wen Jin, Xiaoshan Zhao
Summary: This study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms. The results showed that ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
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)
Article
Biochemistry & Molecular Biology
Ilona Turek, Lubna Freihat, Jignesh Vyas, Janet Wheeler, Victor Muleya, David T. Manallack, Chris Gehring, Helen Irving
Summary: Recent discoveries have identified low-activity guanylate cyclase (GC) catalytic centers within kinase domains in plants, which generate cGMP essential for intramolecular and downstream signaling. Researchers have explored the existence of such cryptic GCs in human proteome and found 18 candidates, including the neurotropic receptor tyrosine kinase 1 (NTRK1). In vitro studies revealed that the embedded NTRK1 GC is functional and exhibits a preference for Mn2+ over Mg2+. These findings suggest previously unsuspected roles of cGMP in intramolecular and downstream signaling of NTRK1, as well as its involvement in NTRK1-dependent growth and neoplasia.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Maria Duszyn, Brygida Swiezawska-Boniecka, Aloysius Wong, Krzysztof Jaworski, Adriana Szmidt-Jaworska
Summary: Recent studies identified a novel receptor BdPepR2 in Brachypodium distachyon, showing both catalytic and kinase activity, with important implications for plant processes. Through bioinformatic analysis, a conserved core catalytic motif was designed, leading to the discovery of potential GCs in monocots.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Rajesh Sharma, Jeong Joo Kim, Liying Qin, Philipp Henning, Madoka Akimoto, Bryan VanSchouwen, Gundeep Kaur, Banumathi Sankaran, Kevin R. MacKenzie, Giuseppe Melacini, Darren E. Casteel, Friedrich W. Herberg, Choel Kim
Summary: This study reveals the mechanisms of auto-inhibition and cGMP relief in PKG I beta through crystal structures and biochemical analysis. The findings suggest that auto-inhibition of PKG I beta is mediated by internal contacts within each monomer, and a model for the regulation and cooperative activation of PKGs is proposed based on the available structural and biochemical data.
Article
Physiology
Suhan Cho, Hyun Namgoong, Hae Jin Kim, Rany Vorn, Hae Young Yoo, Sung Joon Kim
Summary: The study suggests that attenuation of NO/cGMP signaling and upregulation of ROCK2 increase sensitivity to TXA(2) in PAH animals, which may have pathophysiological implications in patients with PAH.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Neurosciences
Ilhuicamina Daniel Limon, Isael Angulo-Cruz, Lesli Sanchez-Abdon, Aleidy Patricio-Martinez
Summary: Glutamate plays vital functions in the nervous system, but changes in glutamatergic neurotransmission caused by hyperammonemia and hepatic failure may lead to hepatic encephalopathy. This condition affects learning, memory, and neuronal communication.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Immunology
Paula Izquierdo-Altarejos, Andrea Cabrera-Pastor, Mar Martinez-Garcia, Carlos Sanchez-Huertas, Alberto Hernandez, Victoria Moreno-Manzano, Vicente Felipo
Summary: Chronic hyperammonemia leads to neuroinflammation, causing cognitive impairment. Extracellular vesicles from mesenchymal stem cells can reduce neuroinflammation. In this study, it was found that treatment with these vesicles restores cognitive function in hyperammonemic rats and the underlying mechanism involves TGF beta signaling.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Lorena Olivares-Gonzalez, Sheyla Velasco, Idoia Gallego, Marina Esteban-Medina, Gustavo Puras, Carlos Loucera, Alicia Martinez-Romero, Maria Pena-Chilet, Jose Luis Pedraz, Regina Rodrigo
Summary: This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs) on retinal degeneration and microglia activation in a mouse model of RP. The EFA supplement improved retinal function, reduced inflammation and microglia activation, and reduced oxidative stress markers. These findings suggest that oral supplementation with SPMs such as the EFA supplement could be a potential therapeutic approach for resolving inflammation in RP.
Article
Nursing
Vanessa Ibanez-del Valle, Maria Luisa Ballestar-Tarin, Mayra Alejandra Mafla-Espana, Omar Cauli, Rut Navarro-Martinez
Summary: This study evaluated the relationship between insomnia and salivary IL-1 beta concentration in older individuals. It found a significant inverse correlation between IL-1 beta levels and insomnia symptoms. Factors such as depression, use of hypnotics, intake of caffeinated beverages, smoking, and alcohol use were also associated with insomnia in this population.
BIOLOGICAL RESEARCH FOR NURSING
(2023)
Article
Biochemistry & Molecular Biology
Paula Izquierdo-Altarejos, Mar Martinez-Garcia, Vicente Felipo
Summary: Patients with liver cirrhosis may experience cognitive impairment due to hyperammonemia and peripheral inflammation, which can also be replicated in rats with chronic hyperammonemia. Neuroinflammation in the hippocampus, caused by peripheral inflammation, alters neurotransmission and leads to cognitive impairment. Extracellular vesicles (EVs) from peripheral blood are believed to play a role in transmitting these peripheral alterations to the brain.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Clinical Neurology
Paola Leone, Yaiza M. Arenas, Tiziano Balzano, Gergana Mincheva, Mar Martinez-Garcia, Carmina Montoliu, Marta Llansola, Vicente Felipo
Summary: This study investigated the presence of neuroinflammation, apoptosis, and neuronal loss in the hippocampus of patients with liver cirrhosis and steatohepatitis. The results showed that patients with steatohepatitis exhibited glial activation, immune cell infiltration, apoptosis, and neuronal loss, while cirrhotic patients only showed glial activation and neuronal loss. These findings may explain the irreversible cognitive impairments observed in hepatic encephalopathy.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alessandra Fiorillo, Juan-Jose Gallego, Franc Casanova-Ferrer, Carla Gimenez-Garzo, Amparo Urios, Maria-Pilar Ballester, Lucia Durban, Maria-Pilar Rios, Javier Megias, Teresa San Miguel, Elena Kosenko, Desamparados Escudero-Garcia, Salvador Benlloch, Vicente Felipo, Carmina Montoliu
Summary: Patients with NAFLD may experience mild cognitive impairment (MCI), and this study identified specific alterations in the immune system that are associated with neurological changes in MCI patients with NAFLD, which may help improve and restore cognitive functions and quality of life in these patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Yaiza M. Arenas, Vicente Felipo
Summary: Chronic hyperammonemia is a major cause of cognitive and motor impairment in hepatic encephalopathy patients. This study aimed to investigate the mechanism involving BDNF, TrkB, NF-kappa B, and various proteins in hyperammonemic rats. The results showed that increased BDNF levels enhanced TrkB activation, leading to PI3K-AKT-NF-kappa B pathway activation and increased content of glutaminase I, HMGB1, and TNF alpha. Blocking TrkB, PI3K, or components of the TNFR1-S1PR2-CCR2-BDNF-TrkB pathway reversed these changes. This TrkB-PI3K-AKT-NF-kappa B pathway activation may contribute to Purkinje neuron dysfunction and motor impairment in hyperammonemic rats and cirrhotic patients with hepatic encephalopathy.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Health Care Sciences & Services
Mayra Alejandra Mafla-Espana, Maria Dolores Torregrosa, Omar Cauli
Summary: Most elderly patients with metastatic prostate cancer should undergo a comprehensive geriatric assessment (CGA) to identify frailty syndrome, which is crucial for clinical decisions. Frailty is associated with lower quality of life and can affect the feasibility and side effects of treatments. Evaluation of frailty syndrome should be considered in clinical decision-making and when selecting the most appropriate active treatment for increased survival.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Health Care Sciences & Services
Mayra Alejandra Mafla-Espana, Maria Dolores Torregrosa, Manel Beamud-Cortes, Lorena Bermell-Marco, Jose Rubio-Briones, Omar Cauli
Summary: Prostate cancer is highly prevalent in males and is associated with frailty symptoms, including decreased gait speed and muscle strength, and increased insomnia symptoms, in patients undergoing androgen-deprivation therapy. Interventions should be implemented to address these issues and improve patient outcomes and quality of life.
Article
Biology
Mar Sempere-Bigorra, Ivan Julian-Rochina, Pilar Perez-Ros, Emmanuel Navarro-Flores, Francisco Miguel Martinez-Arnau, Omar Cauli
Summary: Aging and diabetes both contribute to neurological damage, and this study explores the relationships between peripheral sensory system decline and cognitive functions, symptoms of depression, and quality of life in older adults. The findings suggest that superficial sensitivity damage is related to cognitive impairment, while deep sensation alterations are related to depression and poor quality of life, with diabetes further strengthening these relationships.
Article
Biochemistry & Molecular Biology
Mayra Alejandra Mafla-Espana, Maria Dolores Torregrosa, Manel Beamud-Cortes, Lorena Bermell-Marco, Jose Rubio-Briones, Omar Cauli
Summary: This study investigated the association between blood androgen concentrations and functional status and psychological alterations in prostate cancer patients receiving androgen deprivation therapy. The results showed a significant correlation between high concentrations of androstenedione and frailty syndrome, as well as a relationship between androstenedione levels and decreased gait speed.
Article
Gastroenterology & Hepatology
Yaiza M. Arenas, Paula Izquierdo-Altarejos, Mar Martinez-Garcia, Carla Gimenez-Garzo, Gergana Mincheva, Magnus Doverskog, David E. J. Jones, Tiziano Balzano, Marta Llansola, Vicente Felipo
Summary: Golexanolone treatment may have beneficial effects in improving fatigue, motor, and cognitive impairment in patients with the chronic cholestatic liver disease PBC.
LIVER INTERNATIONAL
(2023)
Article
Medicine, Research & Experimental
Vanessa Ibanez-del Valle, Mayra Alejandra Mafla-Espana, Josep Silva, Omar Cauli, Alessandra Stacchiotti
Summary: Sleep disorders are common in older individuals, especially in those who are institutionalized. They are often comorbid with medical and neuro-psychiatric illnesses and associated with polypharmacy. This study found a significant correlation between salivary IL-6 and sleep parameters, with lower salivary IL-6 levels associated with worse sleep efficiency and more night awakenings. Actigraphy also detected alterations in sleep patterns in individuals with dementia. These results are important for future research and interventions aimed at improving sleep quality in institutionalized individuals.