Article
Biochemistry & Molecular Biology
Gonzalo Ferreira, Axel Santander, Romina Cardozo, Luisina Chavarria, Lucia Dominguez, Nicolas Mujica, Milagros Benitez, Santiago Sastre, Luis Sobrevia, Garth L. Nicolson
Summary: Inwardly rectifying potassium (Kir) channels are important for maintaining membrane potential and potassium homeostasis. These channels have various subtypes and can be regulated by molecules found in nutrients, such as phosphoinositols, polyamines, and Mg2+. Changes in Kir channels can affect metabolism and the ability to absorb nutrients and electrolytes. The study of nutrigenomics of ion channels is crucial for understanding how diet and nutrients can impact ion channel function, expression, and lead to pathological conditions that affect diet and electrolyte intake.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Medicine, Research & Experimental
Peng Shen, Shuangshuo Jia, Yang Wang, Xiaonan Zhou, Delong Zhang, Zhuangzhuang Jin, Ziyuan Wang, Donghao Liu, Lunhao Bai, Yue Yang
Summary: Our study found that lipoxin A4 (LXA4) promotes the polarization of synovial macrophages towards the M2 subtype, inhibiting the nuclear translocation of NF-kappa B p65 and formation of NLRP3 in chondrocytes. Moderate cyclic tensile strain (CTS) and LXA4 both enhance this therapeutic effect. In a rat model of osteoarthritis (OA), treadmill exercise further promotes the M2 polarization of synovial macrophages and protects articular cartilage, and this effect is suppressed by an LXA4 antagonist.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Julianne M. Thornton, Kingsley Yin
Summary: Host response to bacterial infection involves leukocyte activation, inflammatory mediator release, phagocytosis, and killing of bacteria, while resolution of infection requires attenuation of neutrophil migration, neutrophil apoptosis, and other processes. Specialized Pro-resolving Mediators (SPMs) are bioactive fatty acids that play a critical role in promoting the resolution of infectious inflammation and bacterial clearance, including a novel mechanism of reducing bacterial virulence.
Article
Pharmacology & Pharmacy
Martin Machacek, Olga Svecova, Marketa Bebarova
Summary: The study found that sildenafil significantly inhibits IK1 at certain concentrations, and the inhibition effect is more pronounced when used in combination with Ba2+. This combined effect leads to a significant prolongation of action potential duration, potentially contributing to arrhythmias in patients treated with sildenafil.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Louise Reilly, Lee L. Eckhardt
Summary: The potassium inward rectifier channel Kir2 is crucial for cardiac repolarization and membrane stability. Mutations in related genes can lead to sudden cardiac death syndromes. Research focuses on the structure, physiology, and pharmacology of Kir2 channels, as well as their implications for atrial fibrillation treatment and drug safety testing.
Article
Surgery
Meng Wang, Kun Tong, Zhe Chen, Zhengde Wen
Summary: This study aims to investigate the protective effect of LXA4 on cells by inducing HO-1 expression in HPMECs as an in vitro model, and to explain the mechanism of acute lung injury after severe acute pancreatitis.
JOURNAL OF SURGICAL RESEARCH
(2023)
Article
Microbiology
Elizabeth Di Russo Case, Saugata Mahapatra, Caitlyn T. Hoffpauir, Kranti Konganti, Andrew E. Hillhouse, James E. Samuel, Erin J. Van Schaik
Summary: Coxiella burnetii utilizes its secretion system T4SS to survive and replicate in primary macrophages and dampens macrophage proinflammatory responses through effector proteins.
MICROBIOLOGY SPECTRUM
(2022)
Review
Biochemistry & Molecular Biology
Chunshu Li, Yan Yang
Summary: This paper reviews the role of inward rectifier potassium channels (Kir channels) in maintaining the resting membrane potential, signal transduction, and connecting metabolism and membrane excitability. It highlights the close relationship between Kir channels and normal physiological functions as well as the occurrence and development of certain diseases. The functional expression of Kir channels in vascular endothelial cells and smooth muscle cells, and their changes in disease states are discussed, with a particular focus on recent research progress in stem cells. The aim is to deepen our understanding of Kir channels in vascular tissues and provide new ideas and directions for the treatment of related ion channel diseases.
Article
Biochemistry & Molecular Biology
Dongchen An, Steve Peigneur, Jan Tytgat
Summary: The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. WIN55,212-2, a non-selective agonist of CB1 and CB2, activates CB1 and CB2 at low concentrations and blocks GIRK1/2 at high concentrations.
Article
Obstetrics & Gynecology
Veronica M. Gonzalez-Brown, Marwan Ma'ayeh, Douglas A. Kniss, Michael Cackovic, Mark B. Landon, Kara M. Rood
Summary: Daily administration of LDA increases 15-epi-LXA4 levels in high-risk pregnancies for PE, but patients with PE have lower 15-epi-LXA4 levels compared to those without PE.
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH
(2021)
Article
Multidisciplinary Sciences
Xiang Wang, Feng Zhang, Xiaoyi Yan, Guobing Zhang
Summary: The study aimed to investigate the effect of 15E-LXA4 on miR-499 induced cardiac differentiation in CDSCs. Results showed that 15E-LXA4 treatment repressed miR-499 over-expression induced cardiac differentiation, possibly through activation of estrogen receptor to affect signaling pathways.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2021)
Article
Immunology
Fanny Alby-Laurent, Nadia Belaidouni, Benoit Blanchet, Christophe Rousseau, Jean-Francois Llitjos, Sylvia Sanquer, Jean-Paul Mira, Frederic Pene, Julie Toubiana, Jean-Daniel Chiche
Summary: Regulators of TLRs signaling pathways, such as mycophenolate mofetil (MMF), have been shown to play a role in controlling the pro-inflammatory response in sepsis-induced tissue injury. This study found that low-dose MMF treatment improved survival and bacterial clearance in mice infected with Staphylococcus aureus. MMF also enhanced the innate immune response and reduced inflammatory cytokine secretion. The results suggest that MMF has potential as a therapeutic approach for severe infections.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Kara A. Lombardo, Aleksandar Obradovic, Alok Kumar Singh, James L. Liu, Gregory Joice, Max Kates, William Bishai, David McConkey, Alcides Chaux, Marie-Lisa Eich, M. Katayoon Rezaei, George J. Netto, Charles G. Drake, Phuoc Tran, Andres Matoso, Trinity J. Bivalacqua
Summary: In a murine model, BCG instillations elevated STING pathway activation and immune response, leading to tumor eradication, while radiotherapy induced immunosuppressive effects. In human non-muscle-invasive bladder cancer, STING protein expression was elevated in BCG responders and further increased after therapy. Overall, the study suggests that BCG has more beneficial effects on the bladder cancer immune microenvironment compared to radiation therapy.
JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rachel Low, Soon-Duck Ha, Nichita Sleapnicov, Parthiv Maneesh, Sung Ouk Kim
Summary: Macrophages can exhibit low or high responsiveness upon activation, and epigenetic modifications play a crucial role in determining these states. This study investigated the impact of inhibiting the MEK1/2-ERK signaling axis on tolerance and priming in macrophages, finding that prolonged inhibition could reverse these states by decreasing H3K9 methylation levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Sonika Patial, Brandon W. Lewis, Thao Vo, Ishita Choudhary, Kshitiz Paudel, Yun Mao, Dhruthi Singamsetty, Frank Brombacher, Yogesh Saini
Summary: Research has shown that IL-33, ILCs, and IL4R alpha play important roles in the recruitment of eosinophils during normal postnatal lung development in mice. Myeloid-specific IL4R alpha deficiency results in reduced eosinophil numbers in the airspaces and decreased levels of related cytokines.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Paula G. Socuellamos, Luis A. Olivos-Ore, Maria Victoria Barahona, Pilar Cercos, Marta Perez Pascual, Marina Arribas-Blazquez, Jose Ramon Naranjo, Carmen Valenzuela, Marta Gutierrez-Rodriguez, Antonio R. Artalejo
Summary: Neuropathic pain is a chronic form of pain resulting from damage to neural cells. This study evaluated the analgesic effects of IQM-PC332, a new ligand that modulates ion channels, in rats with neuropathic pain. The results showed that IQM-PC332 reduced mechanical sensitivity and modulated ion currents in nerve cells, indicating its potential as a lead compound for novel analgesics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Ana Isabel Moreno-Manuel, Lilian K. Gutierrez, Maria Linarejos Vera-Pedrosa, Francisco Miguel Cruz, Francisco Jose Bermudez-Jimenez, Isabel Martinez-Carrascoso, Patricia Sanchez-Perez, Alvaro Macias, Jose Jalife
Summary: Andersen-Tawil syndrome (ATS) is a rare genetic disease caused by loss-of-function mutations in the KCNJ2 gene, which codes for the Kir2.1 potassium channel. ATS is characterized by variable symptoms including periodic paralysis, life-threatening cardiac arrhythmias, and dysmorphic features. The mechanisms underlying the arrhythmogenic nature of this syndrome are poorly understood, but identifying them is crucial for accurate diagnosis and personalized treatment strategies.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Angela De Benito-Bueno, Paula G. Socuellamos, Yaiza G. Merinero, Pilar Cercos, Carolina Izquierdo, Miguel Daniel-Mozo, Irene Marin-Olivero, Angel Perez-Lara, Juan A. Gonzalez-Vera, Angel Orte, Armando Albert, Mercedes Martin-Martinez, Marta Gutierrez-Rodriguez, Carmen Valenzuela
Summary: DPP6 and KCNE2 modify the pharmacological response of K(V)4.3/KChIP2 channels to IQM-266. IQM-266 decreases the peak of potassium currents and slows down their inactivation. IQM-266 shows a stronger binding preference to Kv4.3/KChIP2 channels in the presence of DPP6, while its binding is abolished in the presence of KCNE2. Moreover, IQM-266 induces an unblocking effect in cells expressing K(V)4.3/KChIP2 and K(V)4.3/KChIP2/KCNE2 during the application of pulse trains.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marina Fuertes-Agudo, Maria Luque-Tevar, Carme Cucarella, Rocio Brea, Lisardo Bosca, Ruben Quintana-Cabrera, Paloma Martin-Sanz, Marta Casado
Summary: COX-2 expression plays a protective role in hepatic ischemia-reperfusion injury, reducing cell necrosis and reactive oxygen species levels, while promoting autophagy, antioxidant, and anti-inflammatory responses. COX-2 also helps maintain mitochondrial function, preventing the degradation of fusion-related protein OPA1 and preserving mitochondrial respiration.
Article
Medicine, Research & Experimental
Marta Paz-Garcia, Adrian Povo-Retana, Rafael I. Jaen, Patricia Prieto, Diego A. Peraza, Carlos Zaragoza, Macarena Hernandez-Jimenez, David Pineiro, Javier Regadera, Maria L. Garcia-Bermejo, E. Macarena Rodriguez-Serrano, Sergio Sanchez-Garcia, Maria A. Moro, Ignacio Lizasoain, Carmen Delgado, Carmen Valenzuela, Lisardo Bosca
Summary: Experimental evidence suggests that controlling the inflammatory response is crucial in reducing cardiac injury after myocardial infarction. An aptamer called 4FT has been investigated for its selective antagonistic effects on human TLR4 in macrophages and a rat model of cardiac ischemia/reperfusion. Treatment with 4FT significantly inhibits TLR4 signaling and improves cardiac injury and markers in the rat model. The expression of inflammatory genes is reduced, while anti-inflammatory genes and pro-resolution molecules are enhanced after 4FT administration, indicating its potential as a therapeutic strategy for preventing cardiac dysfunction after infarction.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Peripheral Vascular Disease
Lucia Diaz S. del Campo, Ana B. Garcia-Redondo, Cristina Rodriguez, Carlos Zaragoza, Santiago Duro-Sanchez, Francesco Palmas, Angela de Benito-Bueno, Paula G. Socuellamos, Diego A. Peraza, Raquel Rodrigues-Diez, Carmen Valenzuela, Jesmond Dalli, Mercedes Salaices, Ana M. Briones
Summary: The study found that there is an imbalance between proinflammatory and resolution mediators in hypertensive patients. Resolvin D2 (RvD2) protects cardiovascular function and structure both as a preventive measure before the development of hypertension and as a treatment for established hypertensive cardiovascular damage, by modulating vascular factors, reducing fibrosis and inflammation.
Article
Endocrinology & Metabolism
Ines Amich, Eduardo Anguita, Silvia Escribano-Serrat, Cristina Alvarez, Diego Rodriguez-Munoz, Veronica Garcia, Rocio Bello, Jose Alberto Pena-Pedrosa, Neus Martinez-Micaelo, Nuria Amigo, Pablo Ortiz, Maria Jose Torrejon, Lisardo Bosca, Javier Martin-Sanchez, Ana Aranda, Susana Alemany
Summary: Metabolic reprogramming is important in fighting COVID-19 infection, and thyroid hormones play a key role in regulating metabolism. This study compared euthyroid patients and those with hypothyroidism treated with levothyroxine (LT4) in terms of biochemical, metabolomic, cytokine, and clinical parameters. No significant differences were found between the two groups, except for TSH and ferritin levels in the ward and TSH and FT4 levels in the ICU. Age was negatively correlated with FT3, and patients with low FT3 and older age had worse prognosis and higher levels of IL-6 and IL-10. A metabolomic cluster indicative of a high ketogenic profile was identified in non-critical hospitalized patients with low FT3 levels.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, Research & Experimental
Diego A. Peraza, Adrian Povo-Retana, Marina Mojena, Ana B. Garcia-Redondo, Pablo Aviles, Lisardo Bosca, Carmen Valenzuela
Summary: Immune cells play a crucial role in the tumor microenvironment, with tumor-associated macrophages (TAMs) having immunosuppressive functions and being considered a therapeutic target in cancer. This study investigated the effects of trabectedin, an antitumor agent, on the tumor microenvironment by analyzing the electrophysiological and molecular phenotype of macrophages.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Alba Vera-Zambrano, Maria Baena-Nuevo, Susanne Rinne, Marta Villegas-Esguevillas, Bianca Barreira, Gokcen Telli, Angela de Benito-Bueno, Antonio Blazquez Jose, Belen Climent, Francisco Perez-Vizcaino, Carmen Valenzuela, Niels Decher, Teresa Gonzalez, Angel Cogolludo
Summary: The study reveals that the chaperone sigma-1 receptor (S1R) plays a crucial role in modulating the expression and activity of KV1.5 channels, and may serve as a new pharmacological target for pathological conditions associated with KV1.5 channel dysfunction, such as pulmonary arterial hypertension and atrial fibrillation. S1R physically interacts with KV1.5 channels and can regulate their expression and function, with low concentrations of S1R increasing and high concentrations decreasing the activity of KV1.5 channels.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Adrian Povo-Retana, Sergio Sanchez-Garcia, Carlota Alvarez-Lucena, Rodrigo Landauro-Vera, Patricia Prieto, Carmen Delgado, Paloma Martin-Sanz, Lisardo Bosca
Summary: The role of extracellular nucleotides in modulating inflammation and cell stress is well-established. These molecules mainly act through the activation of purinergic receptors (P2) on the plasma membrane. P2 receptors can be classified into two families: P2X ion channels and P2Y G protein-coupled receptors. During inflammation, damaged cells release nucleotides, leading to purinergic signaling that influences the synthesis of pro-inflammatory and pro-resolving mediators. Macrophages, under pro-inflammatory conditions, show increased expression and activity of cyclooxygenase 2, resulting in elevated levels of prostaglandin E-2 (PGE(2)). PGE(2) exerts its effects through plasma membrane receptors (EP1-EP4) and intracellular targets, leading to modulation of the inflammatory response and tissue repair.
PURINERGIC SIGNALLING
(2023)
Review
Biochemistry & Molecular Biology
Adrian Povo-Retana, Rodrigo Landauro-Vera, Marco Farinas, Sergio Sanchez-Garcia, Carlota Alvarez-Lucena, Silvia Marin, Marta Cascante, Lisardo Bosca
Summary: Macrophages are vital for both maintaining the balance of healthy organs and defending against pathogens after tissue injury. These cells have different gene expressions, immune functions, and metabolic phenotypes, enabling their involvement in various stages of the inflammatory reaction. Phenotypic differences in macrophages are also observed across different tissues and mammalian species. Although macrophages primarily rely on glycolysis for metabolism, the polarisation and activation of these cells affect their metabolic fluxes. This metabolic and cellular plasticity provides an opportunity to modulate macrophage activity to prevent detrimental effects.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Pharmacology & Pharmacy
Sergio Sanchez-Garcia, Rafael I. Jaen, Maria Fernandez-Velasco, Carmen Delgado, Lisardo Bosca, Patricia Prieto
Summary: An efficient resolution mechanism is crucial for tissue healing after injury or infection. Lipoxins, a type of pro-resolving bioactive lipids, prevent uncontrolled inflammation. They exert their actions through formyl-peptide receptor 2 (ALX/FPR2 receptor) and can also interact with alternative receptors, triggering different signaling pathways to stop inflammation and avoid the development of chronic pathologies.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Geriatrics & Gerontology
Alvaro Macias, Rosa M. Nevado, Cristina Gonzalez-Gomez, Pilar Gonzalo, Maria Jesus Andres-Manzano, Beatriz Dorado, Ignacio Benedicto, Vicente Andres
Summary: HGPS is a rare genetic disease caused by expression of progerin. This disease leads to pathological alterations in the coronary and cerebral arteries, and the mechanisms behind it involve loss of vascular smooth muscle cells and overexpression of K(V)7 channels. The study suggests that targeting K(V)7 channels could be a potential treatment for HGPS.
