Article
Multidisciplinary Sciences
Kotaro Oyama, Vadim Zeeb, Toshiko Yamazawa, Nagomi Kurebayashi, Fuyu Kobirumaki-Shimozawa, Takashi Murayama, Hideto Oyamada, Satoru Noguchi, Takayoshi Inoue, Yukiko U. Inoue, Ichizo Nishino, Yoshie Harada, Norio Fukuda, Shin'ichi Ishiwata, Madoka Suzuki
Summary: This study investigates the relationship between mutant Ryanodine receptor type 1 (RyR1) and malignant hyperthermia (MH) using an optically controlled local heat-pulse method. The results show that RyR1 mutants are more heat sensitive and induce intracellular calcium bursts through heat-induced calcium release (HICR). HICR is also observed in skeletal muscles. This study highlights the complexity of MH and the positive feedback of HICR in thermogenesis in MH patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Anesthesiology
Lourdes Figueroa, Natalia Kraeva, Carlo Manno, Carlos A. Ibarra-Moreno, Eshwar R. Tammineni, Sheila Riazi, Eduardo Rios
Summary: By measuring sensitivity to halothane of myotubes and extending clinical observations and cell-level studies to a large group of patients, new insights into the pathological mechanism of malignant hyperthermia susceptibility have been obtained. Enhanced sensitivity to depolarisation and to halothane appear to be the primary, mutually reinforcing and phenotype-defining defects of halothane-hypersensitive patients with malignant hyperthermia susceptibility.
BRITISH JOURNAL OF ANAESTHESIA
(2023)
Article
Medicine, General & Internal
Luuk R. van den Bersselaar, Nick Kruijt, Gert-Jan Scheffer, Lucas van Eijk, Ignacio Malagon, Stan Buckens, Jose A. E. Custers, Leonie Helder, Anna Greco, Leo A. B. Joosten, Baziel G. M. van Engelen, Nens van Alfen, Sheila Riazi, Susan Treves, Heinz Jungbluth, Marc M. J. Snoeck, Nicol C. Voermans
Summary: This study aims to investigate the comprehensive neuromuscular and multisystem features of RYR1-related MH and ERM, establishing a well-characterized baseline cohort for future research. The study includes questionnaire surveys, clinical observations, imaging, and immunological studies.
Article
Anesthesiology
Yuko Noda, Keiko Mukaida, Hirotsugu Miyoshi, Ryuji Nakamura, Toshimichi Yasuda, Noboru Saeki, Ichizo Nishino, Yasuo M. Tsutsumi
Summary: Dantrolene is currently the only known drug for treating malignant hyperthermia crises. This study found that the presence or absence of RYR1 variants does not affect the effectiveness of dantrolene in muscle cells from individuals predisposed to malignant hyperthermia.
ANAESTHESIA AND INTENSIVE CARE
(2022)
Article
Multidisciplinary Sciences
Zsuzsanna E. Magyar, Judit Hevesi, Linda Groom, Robert T. Dirksen, Janos Almassy
Summary: The T4706M mutation in the RyR1 protein is associated with muscle weakness and alters channel function, leading to a complex mechanism of disease pathogenesis.
SCIENTIFIC REPORTS
(2023)
Article
Anesthesiology
Jean Marcel de Mello, Pamela Vieira Andrade, Joilson Moura Santos, Acary Souza Bulle Oliveira, Mariz Vainzof, Luiz Gomes do Amaral, Helga Cristina Almeida da Silva
Summary: This study aimed to assess variables correlated with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. The results showed that IVCT results were correlated with clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering 0.2g contracture, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation).
BRAZILIAN JOURNAL OF ANESTHESIOLOGY
(2023)
Article
Medicine, Research & Experimental
Davide Servello, Jan Abdinghoff, Alexander Grissmer, Thomas Tschernig
Summary: The study found the presence of TRPC6 channels in human skeletal muscle tissue through immunohistochemistry and confirmed their importance in calcium homeostasis and muscle fiber function. These findings may have significant implications for the treatment of muscular diseases.
BIOMEDICAL REPORTS
(2022)
Review
Cardiac & Cardiovascular Systems
Dimitris Tousoulis, Tomasz Guzik, Teresa Padro, Dirk J. Duncker, Giuseppe De Luca, Etto Eringa, Marija Vavlukis, Alexios S. Antonopoulos, Themistoklis Katsimichas, Edina Cenko, Ana Djordjevic-Dikic, Ingrid Fleming, Olivia Manfrini, Danijela Trifunovic, Charalambos Antoniades, Filippo Crea
Summary: The human gut microbiota plays a crucial role in gastrointestinal function and host physiology, and is linked to the pathogenesis of cardiovascular disease. Compositional and functional alterations of the gut microbiota may be associated with atherosclerosis and coronary artery disease. Targeting the gut microbiota through interventions holds potential for therapeutic strategies.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Laura Micheli, Lara Testai, Andrea Angeli, Donatello Carrino, Alessandra Pacini, Francesco Margiotta, Lorenzo Flori, Claudiu T. Supuran, Vincenzo Calderone, Carla Ghelardini, Lorenzo Di Cesare Mannelli
Summary: Neuropathy development is a major side effect of anticancer treatments, but two compounds 5b and 5d have shown therapeutic and protective effects against paclitaxel-induced neuropathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Hilal Kalkan, Ester Pagano, Debora Paris, Elisabetta Panza, Mariarosaria Cuozzo, Claudia Moriello, Fabiana Piscitelli, Armita Abolghasemi, Elisabetta Gazzerro, Cristoforo Silvestri, Raffaele Capasso, Andrea Motta, Roberto Russo, Vincenzo Di Marzo, Fabio Arturo Iannotti
Summary: This study found that there are changes in the gut microbiota composition, short-chain fatty acids (SCFAs) levels, and related metabolites in the mdx mouse model of Duchenne muscular dystrophy (DMD) compared to healthy controls. Supplementation with sodium butyrate (NaB) in mdx mice showed similar benefits as deflazacort (DFZ) in terms of muscle strength, autophagy, and inflammation. In LPS-stimulated C2C12 myoblasts, NaB reduced inflammation, promoted autophagy, and prevented dysregulation of microRNAs targeting the endocannabinoid CB1 receptor gene through the activation of GPR109A and PPAR gamma receptors. This suggests a potential disease-modifying approach for DMD and other muscular dystrophies.
EMBO MOLECULAR MEDICINE
(2023)
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)
Editorial Material
Cardiac & Cardiovascular Systems
Ingrid Fleming
EUROPEAN HEART JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Veronica Esposito, Daniela Benigno, Ivana Bello, Elisabetta Panza, Mariarosaria Bucci, Antonella Virgilio, Aldo Galeone
Summary: In this study, the structural and biological features of G-quadruplex (G4) aptamers as antiproliferative compounds affecting the STAT3 signalling pathway were investigated. A series of STAT and STATB analogues were prepared to explore their effects on the STAT3 biochemical pathway. These derivatives showed dimeric G4 structures with higher thermal stability and similar antiproliferative activities on human prostate and breast cancer cells. Transcriptomic analysis suggested their potential involvement in STAT3 pathway modulation and interference in different biological processes. These findings provide new tools for affecting the biochemical pathway and developing novel anticancer and anti-inflammatory drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
Article
Biochemistry & Molecular Biology
Ivana Bello, Martina Smimmo, Roberta d'Emmanuele di Villa Bianca, Mariarosaria Bucci, Giuseppe Cirino, Elisabetta Panza, Vincenzo Brancaleone
Summary: Breast cancer is the most common cancer in women, and triple-negative breast cancer (TNBC) is the most severe subtype with the highest mortality rate. This study explored the potential anti-cancer effects of erucin, a compound found in arugula, on TNBC cells. The results showed that erucin effectively inhibited TNBC cell proliferation, induced apoptosis and autophagy, prevented ROS generation, and inhibited cell migration, invasion, and colony formation. Therefore, erucin consumption could be a promising strategy for TNBC intervention.
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.
Article
Cardiac & Cardiovascular Systems
Zhou Zhou, Min Zhang, Chengcheng Zhao, Xu Gao, Zheng Wen, Junfang Wu, Chen Chen, Ingrid Fleming, Jiong Hu, Dao Wen Wang
Summary: Myocarditis is a challenging inflammatory disease of the heart, and EETs and sEH inhibitors can prevent the progression of coxsackie B3 virus-induced myocarditis and promote viral resistance by increasing IFN production.
CIRCULATION RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Charalambos Antoniades, Dimitris Tousoulis, Marija Vavlukis, Ingrid Fleming, Dirk J. Duncker, Etto Eringa, Olivia Manfrini, Alexios S. Antonopoulos, Evangelos Oikonomou, Teresa Padro, Danijela Trifunovic-Zamaklar, Giuseppe De Luca, Tomasz Guzik, Edina Cenko, Ana Djordjevic-Dikic, Filippo Crea
Summary: This article reviews the heterogeneity of adipose tissue depots in humans and emphasizes the interactions between perivascular adipose tissue (PVAT) and the vascular wall. It highlights the potential therapeutic target of PVAT in cardiovascular diseases and its role as a clinically important source of diagnostic and prognostic biomarkers of vascular function. It also discusses recent imaging technologies that visualize PVAT in clinical practice and the integration of PVAT information into prognostic models using artificial intelligence and machine learning technologies.
EUROPEAN HEART JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Antonella Virgilio, Daniela Benigno, Carla Aliberti, Valentina Vellecco, Mariarosaria Bucci, Veronica Esposito, Aldo Galeone
Summary: In this study, three TBA analogues with modified G-tetrads were designed and evaluated. Among them, TBABF showed extraordinary thermal stability, higher anticoagulant activity, and resistance to nucleases. These findings suggest that TBABF is one of the best TBA analogues ever designed and investigated, overcoming limitations in therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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)