Review
Cell Biology
Bogusz Kulawiak, Piotr Bednarczyk, Adam Szewczyk
Summary: Mitochondria play a vital role in the energy metabolism of cardiac cells, and their dysfunction is implicated in cardiac ischemia/reperfusion injury. Understanding mitochondrial K+ channels can provide insights into the mechanisms of cardioprotection.
Article
Cardiac & Cardiovascular Systems
Michael Harris, Junhui Sun, Karen Keeran, Angel Aponte, Komudi Singh, Danielle Springer, Marjan Gucek, Mehdi Pirooznia, Matthew E. Cockman, Elizabeth Murphy, Leslie M. Kennedy
Summary: This study demonstrates that deletion of Ogfod1 alters the myocardial proteome and metabolome, providing protection against ischemia-reperfusion injury.
CARDIOVASCULAR RESEARCH
(2022)
Review
Clinical Neurology
Aqeela Zahra, Ru Liu, Jingjing Wang, Jianping Wu
Summary: Epilepsy is a disease characterized by recurrent seizures caused by increased neuronal excitability. The KCNQ gene encodes Kv7 channels which play a role in inhibiting neuronal excitability. Retigabine, a positive allosteric modulator of KCNQ channels, is the only clinically approved medication that acts on these channels. This review discusses the mechanisms, significance in neuronal pathophysiology, and current stage of development of retigabine in the treatment of epilepsy.
NEUROLOGICAL SCIENCES
(2023)
Article
Cell Biology
Harpreet Singh
Summary: Mitochondria are crucial organelles in cardiac physiology and their dysfunction can lead to heart failure. Ionic homeostasis in mitochondria is closely related to the inner mitochondrial membrane potential, which plays a key role in oxidative metabolism to meet the high energy demands of the heart. Multiple ion transport mechanisms are involved in maintaining the ionic homeostasis in mitochondria, making them attractive therapeutic targets for cardiac diseases.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Giuseppe Alloatti, Claudia Penna, Stefano Comita, Francesca Tullio, Manuela Aragno, Fiorella Biasi, Pasquale Pagliaro
Summary: Although many strong cardioprotective treatments have been identified experimentally in different animal models, the translation of these therapies into clinical practice has been disappointing. Factors such as aging, sex, and inflammation play crucial roles in cardiac ischemic diseases and must be considered in treatment.
VASCULAR PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiao-Fei Zhuang, Yu-Xue Liu, Zhi-Hong Yang, Qin Gao, Lei Wang, Chuanxia Ju, Kewei Wang
Summary: Pharmacological activation of neuronal Kv7 channels has been shown to be a promising strategy for treating epilepsy. The Kv7 channel opener SCR2682 reduces seizure activity and severity in rodent models of epilepsy induced by different triggers, and improves cognitive impairment associated with seizures.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Tamer M. Gamal El-Din, Timothy Lantin, Christopher W. Tschumi, Barbara Juarez, Meagan Quinlan, Julia H. Hayano, Jin Li, Larry S. Zweifel, William A. Catterall
Summary: Autism spectrum disorder affects over 1% of children in the United States, resulting in social interaction deficits, repetitive behaviors, and communication disorders. Genetic analysis through genome sequencing has identified over 500 genes with mutations in ASD, suggesting that altered control of action potential generation by gating pore current through mutant K(v)7 channels may be a potential pathogenic mechanism in autism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cardiac & Cardiovascular Systems
Petra Kleinbongard, Helmut Lieder, Andreas Skyschally, Gerd Heusch
Summary: This study compared the infarct size in female, castrated male, and male pigs undergoing ischemia/reperfusion (I/R) and ischemic preconditioning (IPC). The results showed no sex- or castration-related differences in infarct size, coronary microvascular injury, and cardioprotection by IPC.
CARDIOVASCULAR RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Danfeng Zhang, Bernhard M. Krause, Hans-Gunther Schmalz, Paulus Wohlfart, Benito A. Yard, Rudolf Schubert
Summary: The mechanism by which carbon monoxide (CO) mediates vasodilation is not completely understood, with inconsistency in the types of K+-channels activated by CO releasing molecules (CORMs) in published studies. This study found that Kv7 channels are the main channel through which ET-CORM rac-4 mediates vasodilation, suggesting potential use of ET-CORMs in cardiovascular diseases warrants further in vivo studies.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Ying Luo, Nattayaporn Apaijai, Suchan Liao, Chayodom Maneechote, Titikorn Chunchai, Busarin Arunsak, Juthipong Benjanuwattra, Panat Yanpiset, Siriporn C. Chattipakorn, Nipon Chattipakorn
Summary: Growing evidence suggests that ferroptosis, apoptosis, and necroptosis contribute to cardiac ischemia/reperfusion injury. This study found that apoptosis and ferroptosis, but not necroptosis, contribute to myocardial damage in acute cardiac ischemia/reperfusion injury. Inhibitors of these pathways provided effective cardioprotection through modulation of mitochondrial function and attenuation of apoptosis and ferroptosis.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Andrology
Joongwon Choi, Deok H. Han, Mee R. Chae, Hyun H. Sung, Su J. Kang, Jimin Shin, Sung W. Lee
Summary: The study investigated the molecular characteristics and physiological roles of Kv7 channels in human prostatic smooth muscle (HPrSM). KCNQ4, KCNQ5, and KCNE4 isoforms were predominantly expressed in HPrSM cells, while KCNQ1, KCNQ5, and KCNE3 isoforms were most abundantly expressed in human prostatic tissues. ML213 induced concentration-dependent relaxation of HPrSM strips by activating Kv7.2/7.4/7.5 channels, and this effect was attenuated by pretreatment with the Kv7.1-7.5 blocker XE991.
Article
Neurosciences
Petra Bloms-Funke, Marion Bankstahl, Jens Bankstahl, Christa Kneip, Wolfgang Schroeder, Wolfgang Loescher
Summary: Epilepsy, a common and disabling neurological disorder, requires more effective treatments. GRT-X, a novel anti-seizure drug with a unique dual-mode mechanism of action, shows promising potential in treating epilepsy.
Article
Cell Biology
Igor Khaliulin, Raimondo Ascione, Leonid N. Maslov, Haitham Amal, M. Saadeh Suleiman
Summary: The study demonstrates that 8-Br can alleviate cardiac injury before regional ischemia or at the beginning of reperfusion, protecting the heart from reperfusion damage. This effect may be associated with the inhibition of MPTP through HKII binding to mitochondria.
Article
Cardiac & Cardiovascular Systems
Siavash Beikoghli Kalkhoran, Janos Kriston-Vizi, Sauri Hernandez-Resendiz, Gustavo E. Crespo-Avilan, Ayeshah A. Rosdah, Jarmon G. Lees, Joana Rodrigues Simoes Da Costa, Naomi X. Y. Ling, Jessica K. Holien, Parisa Samangouei, Kroekkiat Chinda, En Ping Yap, Jaime A. Riquelme, Robin Ketteler, Derek M. Yellon, Shiang Y. Lim, Derek J. Hausenloy
Summary: Hydralazine provides acute cardioprotection by inhibiting Drp1-mediated mitochondrial fission.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Martin John Lewis, Igor Khaliulin, Katie Hall, M. Saadeh Suleiman
Summary: This study investigates the effectiveness of cardioprotective intervention in immature hearts and explores the involvement of the mitochondrial permeability transition pore (MPTP). The results demonstrate that immature hearts have a higher innate resistance to ischemia-reperfusion (I/R) injury compared to adult hearts, due to a reduced tendency of MPTP opening following reperfusion. Additionally, simultaneous activation of protein kinase A (PKA) and exchange protein activated by cAMP (Epac) provides cardioprotection that is additive to the innate resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Sara Carpi, Egeria Scoditti, Beatrice Polini, Simone Brogi, Vincenzo Calderone, Peter Proksch, Sherif S. Ebada, Paola Nieri
Summary: The marine environment, particularly sponges with algae, is an untapped source of anticancer compounds. In this study, two compounds (PEL and EPI) extracted from Dactylospongia elegans were found to inhibit melanoma cell growth and induce apoptosis through cell cycle arrest and DNA fragments accumulation. These compounds also affected the expression of miRNAs and their downstream targets, suggesting their potential as lead compounds in anti-melanoma drug research.
Article
Nutrition & Dietetics
Elena Lucarini, Laura Micheli, Eleonora Pagnotta, Alessandra Toti, Valentina Ferrara, Clara Ciampi, Francesco Margiotta, Alma Martelli, Lara Testai, Vincenzo Calderone, Roberto Matteo, Serafino Suriano, Antonio Troccoli, Nicola Pecchioni, Clementina Manera, Lorenzo Di Cesare Mannelli, Carla Ghelardini
Summary: Camelina sativa seed meal has therapeutic effects on colon damage and persistent visceral hypersensitivity associated with colitis in rats, reducing pain and promoting gut healing.
Article
Biochemistry & Molecular Biology
Giulia Bononi, Valentina Citi, Margherita Lapillo, Alma Martelli, Giulio Poli, Tiziano Tuccinardi, Carlotta Granchi, Lara Testai, Vincenzo Calderone, Filippo Minutolo
Summary: SIRT1 is an enzyme that has cardioprotective effects and can be used to treat cardiovascular diseases. We have developed a new SIRT1 activator and found that it has higher activation potency and better cardioprotective properties compared to existing compounds.
Article
Environmental Sciences
Andrea Falco, Prisco Piscitelli, Domenico Vito, Federico Pacella, Cristina Franco, Manuela Pulimeno, Paolo Ambrosino, Javier Arias, Alessandro Miani
Summary: This study investigated the association between COVID-19 infections, hospitalizations or deaths and the extension of public green areas and air pollution. The results showed a significant correlation between the severity of COVID-19 and public green areas and PM2.5 concentrations.
ENVIRONMENTAL RESEARCH
(2023)
Review
Endocrinology & Metabolism
Claudia Aymerich, Borja Pedruzo, Malein Pacho, Marta Laborda, Jon Herrero, Toby Pillinger, Robert A. McCutcheon, Daniel Alonso-Alconada, Marta Bordenave, Maria Martinez-Querol, Ainara Arnaiz, Javier Labad, Paolo Fusar-Poli, Miguel Angel Gonzalez-Torres, Ana Catalan
Summary: Alterations in prolactin and cortisol levels have been found in antipsychotic naive patients with first episode psychosis. This study aims to provide estimates for the standardized mean differences and inter-group variability of these hormone levels in this patient group compared to healthy controls.
PSYCHONEUROENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Andrea Duranti, Gorane Beldarrain, Antonia alvarez, Matilde Sbriscia, Silvia Carloni, Walter Balduini, Daniel Alonso-Alconada
Summary: The endocannabinoid system plays a crucial role in various biological processes, including the development of the nervous system and the response to injuries. It is especially important in preventing and treating vascular disorders and providing neuroprotection after neonatal brain injury. This overview focuses on the components of the endocannabinoid system and its potential as a target for neonatal neuroprotection, particularly in hypoxic-ischemic brain injury.
Review
Pharmacology & Pharmacy
Jacopo Spezzini, Eugenia Piragine, Roberta d'Emmanuele di Villa Bianca, Mariarosaria Bucci, Alma Martelli, Vincenzo Calderone
Summary: Epigenetics studies heritable modifications of genome expression, which do not affect the DNA sequence. Alterations in epigenetic mechanisms can impact phenotype and contribute to disease. Recent evidence suggests that hydrogen sulfide (H2S) plays a role in epigenetic regulation, from DNA methylation to histone modifications and non-coding RNA regulation. This review explores the potential for developing H2S-releasing "epidrugs" for the prevention and treatment of cardiovascular and non-cardiovascular disorders based on its regulatory role in epigenetics.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Lorenzo Flori, Eugenia Piragine, Jacopo Spezzini, Valentina Citi, Vincenzo Calderone, Alma Martelli
Summary: Adipose tissue can be classified into white adipose tissue (WAT) and brown adipose tissue (BAT). Various stimuli can promote the phenotypic change of WAT to a beige phenotype (BeAT), which plays a crucial role in weight control. Polyphenols may induce browning and thermogenesis processes by activating sirtuins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Eugenia Piragine, Davide Petri, Alma Martelli, Vincenzo Calderone, Ersilia Lucenteforte
Summary: Poor adherence to oral antidiabetic drugs (OADs) in patients with type 2 diabetes (T2D) can lead to therapy failure and risk of complications. This study aimed to determine the adherence to OADs in patients with T2D and estimate the association between good adherence and glycemic control. The systematic review and meta-analysis included 156 studies and showed that the proportion of adherent patients was 54%. There was a significant association between good glycemic control and good adherence, indicating that improving adherence could reduce the risk of complications.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Eugenia Piragine, Marco Andrea Malanima, Ersilia Lucenteforte, Alma Martelli, Vincenzo Calderone
Summary: Hydrogen sulfide (H2S) is an endogenous gasotransmitter that plays a role in various biological effects. Imbalanced biosynthesis of H2S has been observed in animal models of age-related diseases, but human studies have inconsistent results. This systematic review and meta-analysis found that circulating levels of H2S were significantly reduced in patients with progressive, chronic, and degenerative diseases compared to healthy individuals. Stratified analysis also showed a significant reduction in circulating H2S levels in patients with vascular disease or kidney disease. These findings suggest that targeting the H2S system may have potential therapeutic benefits for slowing the progression of age-related diseases.
Article
Food Science & Technology
Lucia Recinella, Maria Loreta Libero, Valentina Citi, Annalisa Chiavaroli, Alma Martelli, Roberta Foligni, Cinzia Mannozzi, Alessandra Acquaviva, Simonetta Di Simone, Vincenzo Calderone, Giustino Orlando, Claudio Ferrante, Serena Veschi, Anna Piro, Luigi Menghini, Luigi Brunetti, Sheila Leone
Summary: Multiple studies have shown that aged black garlic has anti-inflammatory, antioxidant, and cardioprotective effects. This study investigated the protective effects of aged black garlic extract (ABGE) alone or in combination with multivitamins on mouse hearts exposed to E. coli lipopolysaccharide. The study also examined the hydrogen sulfide releasing properties and membrane hyperpolarization effect of the formulation composed of ABGE and multivitamins using human aortic smooth muscle cells (HASMCs). The results showed that ABGE, vitamins D and C, and the formulation suppressed the expression of inflammatory genes on mouse hearts and the formulation increased intracellular hydrogen sulfide formation, suggesting its potential use in cardiovascular disease.
Review
Medicine, Research & Experimental
Galliano Zanello, Macarena Garrido-Estepa, Ana Crespo, Daniel O'Connor, Rima Nabbout, Christina Waters, Anthony Hall, Maurizio Taglialatela, Chun-Hung Chan, David A. Pearce, Marc Dooms, Philip John Brooks
Summary: Rare diseases affect a large number of people globally, but very few have approved treatments. Many rare diseases share common underlying molecular causes, which can be targeted for therapy. Grouping rare disease patients based on molecular causes rather than symptoms can increase access to clinical trials. Implementing basket clinical trials based on shared molecular targets has been successful in oncology and is seen as a solution to accelerate the development of new therapies for rare diseases.
EMBO MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Giada Benedetti, Federica Zabini, Luca Tagliavento, Francesco Meneguzzo, Vincenzo Calderone, Lara Testai
Summary: This review summarizes recent preclinical and clinical studies on pomegranate, highlighting its promising beneficial effects in several fields. Further research is needed on key aspects, including limited oral bioavailability and the role of possible active metabolites. The ongoing development of suitable encapsulation and green extraction techniques suggests the great potential of pomegranate and its bioactive constituents as dietary supplements or adjuvants in therapies of cardiovascular and non-cardiovascular diseases.
Article
Biochemistry & Molecular Biology
Valentina Citi, Elisabetta Barresi, Eugenia Piragine, Jacopo Spezzini, Lara Testai, Federico Da Settimo, Alma Martelli, Sabrina Taliani, Vincenzo Calderone
Summary: Metformin, a first-line therapy for type 2 diabetes, has also been evaluated as an anti-cancer agent. Hydrogen sulfide and H2S donors have shown anti-cancer effects, and isothiocyanates have the additional ability to inhibit histone deacetylase enzymes. A new hybrid molecule, Met-ITC, has been designed to release both Met and H2S and has demonstrated higher efficacy in inhibiting cancer cells and affecting the cell cycle compared to Met.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Mathematics, Interdisciplinary Applications
Simone Brogi, Sara Rossi, Roberta Ibba, Stefania Butini, Vincenzo Calderone, Giuseppe Campiani, Sandra Gemma
Summary: This article describes a computational protocol for identifying potential covalent inhibitors of SARS-CoV-2 M-pro and proposes a novel strategy for designing protease inhibitors.