Article
Cell Biology
Simge Kelekci, Abdullah Burak Yildiz, Kenan Sevinc, Deniz Ugurlu Cimen, Tamer Onder
Summary: This article discusses the current status and challenges of research on Friedreich's ataxia, with a focus on the application of animal models, patient-derived materials, and induced pluripotent stem cell models. The article explores the investigation of disease mechanisms and potential therapeutic agents for Friedreich's ataxia using these models.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Clinical Neurology
Gilbert Thomas-Black, Daniel R. Altmann, Harry Crook, Nita Solanky, Ferran Prados Carrasco, Marco Battiston, Francesco Grussu, Marios C. Yiannakas, Baris Kanber, Jasleen K. Jolly, Jon Brett, Susan M. Downes, Marni Moran, Ping K. Chan, Emmanuel Adewunmi, Claudia A. M. Gandini Wheeler-Kingshott, Andrea H. Nemeth, Richard Festenstein, Fion Bremner, Paola Giunti
Summary: This study comprehensively evaluated the degeneration of the retina in FRDA patients and found heterogeneity in different retinal sectors. The thickness of the retinal nerve fiber layer was associated with frataxin levels. These findings have implications for future clinical trial design.
MOVEMENT DISORDERS
(2023)
Review
Pharmacology & Pharmacy
Wenyao Yang, Bruce Thompson, Faith A. A. Kwa
Summary: Friedreich's ataxia is caused by an intronic GAA trinucleotide expansion in the gene, leading to frataxin protein deficiency. Current management focuses on symptomatic relief as there are no treatments to prevent disease progression, highlighting the importance of targeting molecular pathways to alter the course of the condition.
DRUG DISCOVERY TODAY
(2022)
Article
Clinical Neurology
David R. R. Lynch, Melanie P. P. Chin, Sylvia Boesch, Martin B. B. Delatycki, Paola Giunti, Angie Goldsberry, J. Chad Hoyle, Caterina Mariotti, Katherine D. D. Mathews, Wolfgang Nachbauer, Megan O'Grady, Susan Perlman, S. H. Subramony, George Wilmot, Theresa Zesiewicz, Colin J. J. Meyer
Summary: The study evaluated the safety and efficacy of omaveloxolone in patients with Friedreich's ataxia. The results showed a persistent benefit of omaveloxolone treatment on disease course in Friedreich's ataxia.
MOVEMENT DISORDERS
(2023)
Article
Multidisciplinary Sciences
Kevin C. Kemp, Anastasia Georgievskaya, Kelly Hares, Juliana Redondo, Steven Bailey, Claire M. Rice, Neil J. Scolding, Chris Metcalfe, Alastair Wilkins
Summary: This pilot study investigates the potential therapeutic effects of recombinant granulocyte-colony stimulating factor (G-CSF) administration in patients with Friedreich's ataxia (FA). The findings demonstrate that G-CSF treatment is safe in FA patients, and it leads to mobilization of hematopoietic stem cells (HSCs) comparable to that of healthy individuals. Moreover, G-CSF administration results in sustained increases in cellular frataxin concentrations and elevated expression of PGC-1 alpha and Nrf2, indicating its potential clinical impact in FA patients.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Elisabetta Indelicato, Klaus Faserl, Matthias Amprosi, Wolfgang Nachbauer, Rainer Schneider, Julia Wanschitz, Bettina Sarg, Sylvia Boesch
Summary: This study used proteomics analysis to compare muscle samples from FRDA patients and controls, and found significant differences in mitochondrial protein profiles and metabolic pathways. These findings have important implications for the design of future therapeutic strategies.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Neurosciences
Beata Monfort, Kristian Want, Sylvain Gervason, Benoit D'Autreaux
Summary: Friedreich's ataxia (FRDA) is a prevalent autosomic recessive ataxia that is associated with severe cardiac hypertrophy and less commonly, diabetes. It is caused by mutations in the gene encoding frataxin, a mitochondrial protein involved in iron metabolism. Recent discoveries suggest that frataxin functions as an accelerator in the biosynthesis of Fe-S clusters, which may have implications for the development of therapeutic treatments for FRDA.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Suran Nethisinghe, Maheswaran Kesavan, Heather Ging, Robyn Labrum, James M. Polke, Saiful Islam, Hector Garcia-Moreno, Martina F. Callaghan, Francesca Cavalcanti, Mark A. Pook, Paola Giunti
Summary: Studies have shown that small interruptions at the 3' end of the GAA repeat tract are more common in FRDA patients, with 3' interruptions being the most frequent. Patients with 3' interruptions are associated with shorter GAA1 repeat tracts and later ages at disease onset. Model predictions suggest that a 3' interruption may delay disease onset by approximately 9 years compared to patients lacking interruptions. This highlights the significant impact of 3' interruptions on modulating the disease phenotype and prognosis for the patient.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Jurate Skerniskyte, Celine Mulet, Antonin C. Andre, Mark C. Anderson, Louise Injarabian, Achim Buck, Verena M. Prade, Philippe J. Sansonetti, Sophie Reibel-Foisset, Axel K. Walch, Michel Lebel, Jens Lykkesfeldt, Benoit S. Marteyn
Summary: Shigella spp. are bacterial pathogens that cause bacterial dysentery and shigellosis, primarily in children in developing countries. The lack of a suitable animal model has hindered the study of the complete life cycle of Shigella in vivo and the evaluation of vaccine candidates' efficacy. By inducing moderate ascorbate deficiency in guinea pigs and using a Gulo-/- mouse infection model, researchers found that vitamin C deficiency increased the severity of shigellosis symptoms and Shigella penetration into the colon epithelium layer. These new rodent models provide new opportunities for studying Shigella infection strategies and immune responses.
Article
Multidisciplinary Sciences
Riccardo Turchi, Francesca Sciarretta, Veronica Ceci, Marta Tiberi, Matteo Audano, Silvia Pedretti, Concetta Panebianco, Veronica Nesci, Valerio Pazienza, Alberto Ferri, Simone Carotti, Valerio Chiurchiu, Nico Mitro, Daniele Lettieri-Barbato, Katia Aquilano
Summary: Friedreich's ataxia (FA) is a neurodegenerative disease caused by a mutation in the FXN gene, leading to deficiency of mitochondrial frataxin. This study investigated the role of visceral white adipose tissue (vWAT) in FA-related metabolic complications. The findings suggest that vWAT abnormalities contribute to metabolic issues in FA, and a butyrate-enriched diet may be a safe and promising adjunct for FA management.
Article
Biochemistry & Molecular Biology
Urja Verma, Maheswor Gautam, Bhaval Parmar, Kashmira Khaire, David S. Wishart, Suresh Balakrishnan
Summary: The study found that COX-2 is functionally active during chick embryogenesis, impacting the structural configuration of multiple organs and tissues primarily through regulation of PGE(2) levels. Inhibition of COX-2 resulted in significant developmental anomalies, while compensatory increase in COX-1 activity helped maintain levels of other effector prostanoids. Among the three prostanoids studied, PGE(2) appeared to be predominantly regulated by activated COX-2 in this process.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Review
Pharmacology & Pharmacy
Zhiran Ju, Menglan Li, Junde Xu, Daniel C. Howell, Zhiyun Li, Fen-Er Chen
Summary: Cyclooxygenases play a vital role in inflammation, but currently used anti-inflammatory drugs have associated adverse effects. Researchers are searching for novel selective COX-2 inhibitors.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Infectious Diseases
Kamil Faltin, Zuzanna Lewandowska, Pawel Malecki, Krzysztof Czyz, Emilia Szafran, Agnieszka Kowalska-Tupko, Anna Mania, Katarzyna Mazur-Melewska, Katarzyna Jonczyk-Potoczna, Waldemar Bobkowski, Magdalena Figlerowicz
Summary: This article presents a case of a 17-year-old boy with Friedreich's ataxia-induced hypertrophic cardiomyopathy who contracted COVID-19. Despite mild initial symptoms, the patient's condition deteriorated rapidly, requiring antiarrhythmic treatment, pharmacological intervention, and convalescent plasma therapy.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Jessica Tiberi, Marco Segatto, Maria Teresa Fiorenza, Piergiorgio La Rosa
Summary: Friedreich's ataxia is a neurodegenerative disease caused by the loss of frataxin activity, leading to mitochondrial dysfunctions and oxidative stress. The GAA expansion in the FXN gene inhibits transcription and disrupts iron metabolism. The defective NRF2 functionality further contributes to the disease progression. Antioxidant therapies have shown conflicting results in preclinical and clinical studies, highlighting the need for further research and understanding of the underlying mechanisms.
Review
Endocrinology & Metabolism
Prashanth Anamthathmakula, Wipawee Winuthayanon
Summary: The mammalian oviduct plays a crucial role in important reproductive events, and PTGS2 is significantly involved in early pregnancy processes. Studying PTGS2 signaling in the oviduct is essential for understanding reproduction and may have implications for assisted reproductive technology.
Review
Dermatology
Karan Agrawal, Raja K. Sivamani, John W. Newman
SKIN RESEARCH AND TECHNOLOGY
(2019)
Article
Multidisciplinary Sciences
Anita Rajamani, Kamil Borkowski, Samir Akre, Andrea Fernandez, John W. Newman, Scott Simon, Anthony G. Passerini
SCIENTIFIC REPORTS
(2019)
Article
Chemistry, Analytical
Theresa L. Pedersen, Ira J. Gray, John W. Newman
Summary: The goal of this research was to develop a high-throughput, cost-effective method for metabolic profiling of lipid mediators and hormones involved in the regulation of inflammation and energy metabolism. The method showed low intra- and inter-batch variability for most metabolites, but higher variability for serum oxylipins and some bile acids. Application to two cohorts of elderly individuals revealed routine detection of 86 metabolites and provided valuable insights for large cohort studies.
ANALYTICA CHIMICA ACTA
(2021)
Article
Nutrition & Dietetics
Riley L. Hughes, William H. Horn, Peter Finnegan, John W. Newman, Maria L. Marco, Nancy L. Keim, Mary E. Kable
Summary: The study found that consumption of RS2-enriched wheat leads to reduced postprandial glycemia, altered gut microbiota composition, and increased fermentation activity.
Article
Biochemistry & Molecular Biology
Tagreed A. Mazi, Kamil Borkowski, John W. Newman, Oliver Fiehn, Christopher L. Bowlus, Souvik Sarkar, Karen Matsukuma, Mohamed R. Ali, Dorothy A. Kieffer, Yu-Jui Y. Wan, Kimber L. Stanhope, Peter J. Havel, Valentina Medici
Summary: In this study, Hispanics were found to have a higher rate and severity of nonalcoholic fatty liver disease compared to other ethnicities. Metabolomic profiling showed signs of metabolic dysregulation in Hispanics, independent of obesity, with higher plasma triglycerides and free fatty acids. Ethnicity-related differences in liver and plasma metabolomic profiles may modulate the risk for progression of NAFLD to NASH.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Sridevi Krishnan, Erik R. Gertz, Sean H. Adams, John W. Newman, Theresa L. Pedersen, Nancy L. Keim, Brian J. Bennett
Summary: The study showed that following a diet based on the 2010 Dietary Guidelines for Americans for 8 weeks did not improve endothelial function or reduce plasma TMAO concentrations.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Deena B. Snoke, Austin Angelotti, Kamil Borkowski, Rachel M. Cole, John W. Newman, Martha A. Belury
Summary: Dietary lipid sources have a significant impact on lipid mediator profiles in adipose tissues and plasma, which in turn affects energy metabolism. Changes in lipid mediators vary between tissues, and these mediators play important roles in regulating adipose tissue expansion and function. There is a relationship between brown adipose tissue and plasma lipid mediators in mice consuming a linoleate-rich safflower oil diet.
Article
Biochemistry & Molecular Biology
Celine Dalle, Jeremy Tournayre, Malwina Mainka, Alicja Basiak-Rasala, Melanie Petera, Sophie Lefevre-Arbogast, Jessica Dalloux-Chioccioli, Melanie Deschasaux-Tanguy, Lucie Lecuyer, Emmanuelle Kesse-Guyot, Leopold K. Fezeu, Serge Hercberg, Pilar Galan, Cecilia Samieri, Katarzyna Zatonska, Philip C. Calder, Mads Fiil Hjorth, Arne Astrup, Andre Mazur, Justine Bertrand-Michel, Nils Helge Schebb, Andrzej Szuba, Mathilde Touvier, John W. Newman, Cecile Gladine
Summary: The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Bruce A. Watkins, Allon N. Friedman, Jeffrey Kim, Kamil Borkowski, Shaun Kaiser, Oliver Fiehn, John W. Newman
Summary: Hemodialysis patients have higher blood pressure, inflammation levels, and cardiovascular disease risk compared to healthy subjects. They also have unusually low levels of n-3 polyunsaturated fatty acids. This study found that these differences in specific fatty acid levels resulted in changes in endocannabinoids and oxylipins, which help explain the severe inflammation and cardiovascular disease observed in these patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Austin Angelotti, Deena B. Snoke, Kate Ormiston, Rachel M. Cole, Kamil Borkowski, John W. Newman, Tonya S. Orchard, Martha A. Belury
Summary: Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) may alleviate chemotherapy-induced cardiotoxicity by modulating heart gene expression and lipid species.
Article
Biochemistry & Molecular Biology
Kristen L. James, Erik R. Gertz, Catherine P. Kirschke, Hooman Allayee, Liping Huang, Mary E. Kable, John W. Newman, Charles B. Stephensen, Brian J. Bennett
Summary: In this study, a mixed macronutrient tolerance test was conducted to investigate the changes in plasma TMAO levels in response to different factors. It was found that TMAO levels increased with age in females but not in males. The relationship between TMAO levels and fecal microbiome and FMO3 genotype was limited, while a strong correlation between TMAO levels and TNF-alpha was observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Iryna Rybak, Kelly N. Haas, Simran K. Dhaliwal, Waqas A. Burney, Aunna Pourang, Simran S. Sandhu, Jessica Maloh, John W. Newman, Robert Crawford, Raja K. Sivamani
Summary: This study aimed to investigate the effects of oral spore-based probiotic ingestion on the gut microbiome, plasma short-chain fatty acids (SCFAs), and skin biophysical properties. The results showed that probiotic supplementation led to a decrease in facial sebum excretion rate and an overall increase in transepidermal water loss (TEWL). Participants with acne showed improvements in lesion counts and markers of gut permeability. The gut microbiome of the nonacne population had an increase in Akkermansia, while those with acne had an increase in Lachnospiraceae and Ruminococcus gnavus. Preliminary evidence suggests the potential use of spore-based probiotic supplementation for modulating the gut microbiome and increasing SCFAs in both acne and nonacne populations.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Nutrition & Dietetics
Bruce A. Watkins, John W. Newman, George A. Kuchel, Oliver Fiehn, Jeffrey Kim
Summary: This study investigated the effects of dietary polyunsaturated fatty acids (PUFA) on the endocannabinoid system (ECS) and found that DHA-enriched diet can alter energy metabolism and fatty acid metabolism, reducing the risk of obesity and type 2 diabetes.
Article
Biochemistry & Molecular Biology
Anita Wen, Ying Zhu, Sook Wah Yee, Brian I. Park, Kathleen M. Giacomini, Andrew S. Greenberg, John W. Newman
Summary: The Thiamine Transporter 2 (THTR2) encoded by SLC19A3 plays an undefined role in maintaining tissue thiamine levels. In this study, the impact of THTR2 on thiamine status and metabolism was evaluated in mice. The loss of THTR2 resulted in lower plasma and brain thiamine levels and altered brain metabolome. This suggests that THTR2 mutation or inhibition may affect thiamine storage and metabolism in the brain.
Article
Nutrition & Dietetics
Virginia M. Artegoitia, Sridevi Krishnan, Ellen L. Bonnel, Charles B. Stephensen, Nancy L. Keim, John W. Newman
Summary: The study revealed that differences in dietary patterns by sex and age can help individuals distinguish whether they have risk factors for cardiometabolic disease, and sex-specific dietary patterns can more accurately predict the presence of CMDrf.