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MULTICENTER STUDY
Borja Quiroga, María José Soler, Alberto Ortiz, Carlos Jesús Jarava Mantecón, Virginia Olinda Gomes Pérez, Antoni Bordils, José Lacueva, Antonio José Marin Franco, Pablo Delgado Conde, Patricia Muñoz Ramos, Carmen Calderón González, Juan Manuel Cazorla López, Jinny Sanchez-Rodriguez, Ana Sánchez Horrillo, Tania Raquel Monzón Vázquez, Alba Leyva, José Rojas, Ron T Gansevoort, Patricia de Sequera
BACKGROUND: There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity...
March 31, 2023: Nephrology, Dialysis, Transplantation
#22
JOURNAL ARTICLE
David Siegel, Peter S Harris, Cole R Michel, Rafael de Cabo, Kristofer S Fritz, David Ross
The stress induced protein NQO1 can participate in a wide range of biological pathways which are dependent upon the interaction of NQO1 with protein targets. Many of the protein-protein interactions involving NQO1 have been shown to be regulated by the pyridine nucleotide redox balance. NQO1 can modify its conformation as a result of redox changes in pyridine nucleotides and sites on the C-terminal and helix seven regions of NQO1 have been identified as potential areas that may be involved in redox-dependent protein-protein interactions...
2022: Frontiers in Pharmacology
#23
JOURNAL ARTICLE
Albaro José Nieto-Calvache, José Enrique Sanín-Blair, Haidi Marcela Buitrago-Leal, Jesús Andrés Benavides-Serralde, Juliana Maya-Castro, Adda Piedad Rozo-Rangel, Adriana Messa-Bryon, Alejandro Colonia-Toro, Armando Rafael Gómez-Castro, Arturo Cardona-Ospina, Carlos Eduardo Caicedo-Cáceres, Elkin Fabian Dorado-Roncancio, Jaime Luis Silva, Javier Andrés Carvajal-Valencia, Jesús Arnulfo Velásquez-Penagos, Jorge Ernesto Niño-González, Juan Manuel Burgos-Luna, Juan Carlos Rincón-García, Lía Matera-Torres, Orlando Afranio Villamizar-Galvis, Sandra Ximena Olaya-Garay, Virna Patricia Medina-Palmezano, Jimmy Castañeda
INTRODUCTION: Placenta accreta spectrum (PAS) is a condition associated with massive postpartum bleeding and maternal mortality. Management guidelines published in high income countries recommend the participation of interdisciplinary teams in hospitals with sufficient resources for performing complex procedures. However, some of the recommendations contained in those guidelines are difficult to implement in low and medium income countries. OBJECTIVES: The aim of this consensus is to draft general recommendations for the treatment of PAS in Colombia...
September 30, 2022: Revista Colombiana de Obstetricia y Ginecología
#24
JOURNAL ARTICLE
Naomi Dirckx, Qian Zhang, Emily Y Chu, Robert J Tower, Zhu Li, Shenghao Guo, Shichen Yuan, Pratik A Khare, Cissy Zhang, Angela Verardo, Lucy O Alejandro, Angelina Park, Marie-Claude Faugere, Stephen L Helfand, Martha J Somerman, Ryan C Riddle, Rafael de Cabo, Anne Le, Klaus Schmidt-Rohr, Thomas L Clemens
Citrate is a critical metabolic substrate and key regulator of energy metabolism in mammalian cells. It has been known for decades that the skeleton contains most (>85%) of the body's citrate, but the question of why and how this metabolite should be partitioned in bone has received singularly little attention. Here, we show that osteoblasts use a specialized metabolic pathway to regulate uptake, endogenous production, and the deposition of citrate into bone. Osteoblasts express high levels of the membranous Na+ -dependent citrate transporter solute carrier family 13 member 5 ( Slc13a5 ) gene...
November 8, 2022: Proceedings of the National Academy of Sciences of the United States of America
#25
JOURNAL ARTICLE
Sudipta Panja, David Siegel, Simonetta Camandola, Rafael de Cabo, David Ross, Krishna Mallela
Alzheimer's disease is one of the most prominent neurodegenerative diseases. Results from animal and cellular models suggest that FAD-deficient forms of NQO1 may accelerate the aggregation of Alzheimer's amyloid beta peptide Ab1-42. Here we examined in-vitro whether NQO1 and its FAD-deficient P187S mutation (NQO1*2) directly interact with Ab1-42 and modify its rate of aggregation. When monitored using the fluorescence of either non-covalent thioflavin T or HiLyte Fluor 647 dye covalently attached to the Ab1-42 peptide, the aggregation kinetics of Ab1-42 were markedly more rapid in the presence of NQO1*2 than the wild-type NQO1...
October 25, 2022: Bioscience Reports
#26
JOURNAL ARTICLE
Carlos Anerillas, Allison B Herman, Rachel Munk, Amanda Garrido, Kwan-Wood Gabriel Lam, Matthew J Payea, Martina Rossi, Dimitrios Tsitsipatis, Jennifer L Martindale, Yulan Piao, Krystyna Mazan-Mamczarz, Jinshui Fan, Chang-Yi Cui, Supriyo De, Kotb Abdelmohsen, Rafael de Cabo, Myriam Gorospe
Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory and tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions aim at selectively eliminating senescent cells. In this study, a drug library screen uncovered TrkB (NTRK2) inhibitors capable of triggering apoptosis of several senescent, but not proliferating, human cells. Senescent cells expressed high levels of TrkB, which supported senescent cell viability, and secreted the TrkB ligand BDNF...
October 20, 2022: Nature Communications
#27
JOURNAL ARTICLE
Francisca Artigues Serra, Mercedes García-Gasalla, Antoni Campins, Miguel González de Cabo, Rafael Morales, Rebecca Rowena Peña, María Carmen Gallegos, Melchor Riera
RATIONALE: Since its first identification in the early 1990s, Mycobacterium genavense has been considered and opportunistic pathogen. It mainly causes gastrointestinal symptoms, but also disseminated infections in severely immunosuppressed patients. Sclerosing mesenteritis is a long-term complication with high morbidity and mortality. As it is a rare condition, there are no specific guidelines for its management. We report a challenging case of persistent M. genavense infection, and propose surgery as an alternative treatment strategy...
September 9, 2022: Medicine (Baltimore)
#28
JOURNAL ARTICLE
Stefano Porru, Maria Grazia Lourdes Monaco, Gianluca Spiteri, Angela Carta, Maria Diletta Pezzani, Giuseppe Lippi, Davide Gibellini, Evelina Tacconelli, Ilaria Dalla Vecchia, Emma Sala, Emanuele Sansone, Giuseppe De Palma, Carlo Bonfanti, Massimo Lombardo, Luigina Terlenghi, Enrico Pira, Ihab Mansour, Maurizio Coggiola, Catalina Ciocan, Alessandro Godono, Adonina Tardon, Marta-Maria Rodriguez-Suarez, Guillermo Fernandez-Tardon, Francisco-Jose Jimeno-Demuth, Rafael-Vicente Castro-Delgado, Tania Iglesias Cabo, Maria Luisa Scapellato, Filippo Liviero, Angelo Moretto, Paola Mason, Sofia Pavanello, Anna Volpin, Luigi Vimercati, Silvio Tafuri, Luigi De Maria, Stefania Sponselli, Pasquale Stefanizzi, Antonio Caputi, Fabriziomaria Gobba, Alberto Modenese, Loretta Casolari, Denise Garavini, Cristiana D'Elia, Stefania Mariani, Francesca Larese Filon, Luca Cegolon, Corrado Negro, Federico Ronchese, Francesca Rui, Paola De Michieli, Nicola Murgia, Marco Dell'Omo, Giacomo Muzi, Tiziana Fiordi, Angela Gambelunghe, Ilenia Folletti, Dana Mates, Violeta Claudia Calota, Andra Neamtu, Ovidiu Perseca, Catalin Alexandru Staicu, Angelica Voinoiu, Eleonóra Fabiánová, Jana Bérešová, Zora Kľocová Adamčáková, Roman Nedela, Anna Lesňáková, Jana Holčíková, Paolo Boffetta, Mahsa Abedini, Giorgia Ditano, Shuffield Seyram Asafo, Giovanni Visci, Francesco Saverio Violante, Carlotta Zunarelli, Giuseppe Verlato
BACKGROUND: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. METHODS: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion)...
July 27, 2022: Vaccines
#29
JOURNAL ARTICLE
Léa Montégut, Rafael de Cabo, Laurence Zitvogel, Guido Kroemer
In population studies, dietary patterns clearly influence the development, progression, and therapeutic response of cancers. Nonetheless, interventional dietary trials have had relatively little impact on the prevention and treatment of malignant disease. Standardization of nutritional interventions combined with high-level mode-of-action studies holds the promise of identifying specific entities and pathways endowed with antineoplastic properties. Here, we critically review the effects of caloric restriction and more specific interventions on macro- and micronutrients in preclinical models as well as in clinical studies...
August 23, 2022: Cancer Discovery
#30
JOURNAL ARTICLE
Laura C D Pomatto-Watson, Monica Bodogai, Melissa Carpenter, Dolly Chowdhury, Priya Krishna, Sandy Ng, Oye Bosompra, Jonathan Kato, Sarah Wong, Carlos Reyes-Sepulveda, Michel Bernier, Nathan L Price, Arya Biragyn, Rafael de Cabo
Caloric restriction (CR) is the leading non-pharmacological intervention to delay induced and spontaneous tumors in pre-clinical models. These effects of CR are largely attributed to canonical inhibition of pro-growth pathways. However, our recent data suggest that CR impairs primary tumor growth and cancer progression in the murine 4T1 model of triple negative breast cancer (TNBC), at least in part, through reduced frequency of the myeloid-derived suppressor cells (MDSC). In the present study, we sought to determine whether injection of excess MDSCs could block regression in 4T1 tumor growth and metastatic spread in BALB/cJ female mice undergoing daily CR...
August 23, 2022: GeroScience
#31
JOURNAL ARTICLE
Juan Diego Hernández-Camacho, Daniel J M Fernández-Ayala, Cristina Vicente-García, Ignacio Navas-Enamorado, Guillermo López-Lluch, Clara Oliva, Rafael Artuch, Judith Garcia-Villoria, Antonia Ribes, Rafael de Cabo, Jaime J Carvajal, Plácido Navas
ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months...
2022: Frontiers in Physiology
#32
JOURNAL ARTICLE
Michel Bernier, Ignacio Navas Enamorado, Mari Carmen Gómez-Cabrera, Miguel Calvo-Rubio, Jose Antonio González-Reyes, Nathan L Price, Ana Belén Cortés-Rodríguez, Juan Carlos Rodríguez-Aguilera, Sandra Rodríguez-López, Sarah J Mitchell, Kelsey N Murt, Krystle Kalafut, Katrina M Williams, Christopher W Ward, Joseph P Stains, Gloria Brea-Calvo, Jose M Villalba, Sonia Cortassa, Miguel A Aon, Rafael de Cabo
Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group's exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear...
June 27, 2022: NPJ Aging
#33
JOURNAL ARTICLE
María Tiana, Elena Lopez-Jimenez, Julio Sainz de Aja, Antonio Barral, Jesus Victorino, Claudio Badia-Careaga, Isabel Rollan, Raquel Rouco, Elisa Santos, Hector Sanchez-Iranzo, Rafael D Acemel, Carlos Torroja, Javier Adan, Eduardo Andres-Leon, Jose Luis Gomez-Skarmeta, Giovanna Giovinazzo, Fatima Sanchez-Cabo, Miguel Manzanares
Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation...
July 15, 2022: Science Advances
#34
JOURNAL ARTICLE
Jack M Moen, Christopher H Morrell, Michael G Matt, Ismayil Ahmet, Syevda Tagirova, Moran Davoodi, Michael Petr, Shaquille Charles, Rafael de Cabo, Yael Yaniv, Edward G Lakatta
The combined influences of sinoatrial nodal (SAN) pacemaker cell automaticity and its response to autonomic input determine the heart's beating interval variability and mean beating rate. To determine the intrinsic SAN and autonomic signatures buried within EKG RR interval time series change in advanced age, we measured RR interval variability before and during double autonomic blockade at 3-month intervals from 6 months of age until the end of life in long-lived (those that achieved the total cohort median life span of 24 months and beyond) C57/BL6 mice...
June 27, 2022: GeroScience
#35
JOURNAL ARTICLE
David G Le Couteur, David Raubenheimer, Samantha Solon-Biet, Rafael de Cabo, Stephen J Simpson
Nutrition profoundly influences the risk for many age-related diseases. Whether nutrition influences human aging biology directly is less clear. Studies in different animal species indicate that reducing food intake ('caloric restriction', CR) can increase lifespan and delay the onset of diseases and the biological hallmarks of aging. Obesity has been described as 'accelerated aging' and therefore the lifespan and health benefits generated by CR in both aging and obesity may occur via similar mechanisms. Beyond calorie intake, studies based on nutritional geometry have shown that protein intake and the interaction between dietary protein and carbohydrates influence age-related health and lifespan...
June 14, 2022: Journal of Internal Medicine
#36
JOURNAL ARTICLE
Miguel A Aon, Michel Bernier, Rafael de Cabo
Distinct and shared pathways of health and lifespan can be untangled following a concerted approach led by experimental design and a rigorous analytical strategy where the confounding effects of diet and feeding regimens can be dissected. In this chapter, we use integrated analysis of multiomics (transcriptomics-metabolomics) data in liver from mice to gain insight into pathways associated with improved health and survival. We identify a unique metabolic hub involving glycine-serine-threonine metabolism at the core of lifespan, and a pattern of shared pathways related to improved health...
2022: Methods in Molecular Biology
#37
JOURNAL ARTICLE
Sara López-Bellón, Sandra Rodríguez-López, José A González-Reyes, M Isabel Burón, Rafael de Cabo, José M Villalba
Cytochrome b5 reductase 3 (CYB5R3) overexpression activates respiratory metabolism and exerts prolongevity effects in transgenic mice, mimicking some of the salutary effects of calorie restriction. The aim of our study was to understand how CYB5R3 overexpression targets key pathways that modulate the rate of aging in skeletal muscle, a postmitotic tissue with a greater contribution to resting energy expenditure. Mitochondrial function, autophagy and mitophagy markers were evaluated in mouse hind limb skeletal muscles from young-adult (7 months old) and old (24 months old) males of wild-type and CYB5R3-overexpressing genotypes...
May 9, 2022: GeroScience
#38
JOURNAL ARTICLE
Jessica L Lee, Cissy Zhang, Reyhan Westbrook, Mariann M Gabrawy, Lolita Nidadavolu, Huanle Yang, Ruth Marx, Yuqiong Wu, Nicole M Anders, Lina Ma, Marcela-Dávalos Bichara, Min-Ji Kwak, Brian Buta, Mohammed Khadeer, Gayane Yenokyan, Jing Tian, Qian-Li Xue, Helmy M Siragy, Robert M Carey, Rafael de Cabo, Luigi Ferrucci, Ruin Moaddel, Michelle A Rudek, Anne Le, Jeremy D Walston, Peter M Abadir
Losartan is an oral antihypertensive agent that is rapidly metabolized to EXP3174 (angiotensin-subtype-1-receptor-blocker) and EXP3179 (peroxisome-proliferator-activated-receptor-gamma [PPARγ] agonist), which was shown in animal studies to reduce inflammation, enhance mitochondrial energetics, and improve muscle repair and physical performance. We conducted an exploratory pilot study evaluating losartan treatment in prefrail older adults (age 70-90 years, N=25). Participants were randomized to control (placebo) or treatment (daily oral losartan beginning at 25 mg per day and increasing every eight weeks) for a total of 6 months...
May 3, 2022: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
#39
JOURNAL ARTICLE
Abdul-Ilah Hachem, Marcos Del Carmen-Rodriguez, Rondanelli S Rafael, Xavier Rius, Andres Molina-Creixell, Pablo Cañete San Pastor, Javier Hernandez-Gañan, Francisco Javier Cabo Cabo
INTRODUCTION: Anterior glenohumeral bone loss reconstruction reduces failure rates after soft tissue surgery in patients with large glenoid bone defects. Multiple bone block techniques have been described, most with metal hardware fixation. The objective of this study is to evaluate the safety, as well as the short term functional and radiological results of an arthroscopic bone block metal-free fixation or Bone Block Cerclage (BBC). MATERIALS AND METHODS: Retrospective study of patients with glenohumeral instability and >15% glenoid bone loss operated during 2019 with follow-up (FU) of at least 12 months...
April 26, 2022: Revista Española de Cirugía Ortopédica y Traumatología
#40
COMMENT
Isabel Beerman, Nathan Basisty, Rafael de Cabo
Increased age is blamed for a wide range of bone physiological changes, and although the underlying mechanisms affecting the decreased capacity for fracture healing are not fully understood, they are clearly linked to changes at the cellular level. Recent evidence suggests potential roles of senescent cells in response to most tissue injuries, including bone fractures. In this issue of the JCI, Liu, Zhang, and co-authors showed that a senolytic drug cocktail cleared senescent cells from the callus and improved bone fracture repair in aged mice...
April 15, 2022: Journal of Clinical Investigation
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