Article
Gastroenterology & Hepatology
Ismael Gomez-Martinez, R. Jarrett Bliton, Keith A. Breau, Michael J. Czerwinski, Ian A. Williamson, Jia Wen, John F. Rawls, Scott T. Magness
Summary: Through single-cell RNA sequencing, it was found that the expression of lipid-handling genes increases as absorptive enterocytes mature. Culture conditions promote differentiation of intestinal stem cells into dense absorptive enterocyte monolayers. Fatty acid oxidation modulation affects fatty acid export, while short-chain fatty acids are unaffected.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Plant Sciences
Hao Hu, Armond Swift, Margarita Mauro-Herrera, James Borrone, Guadalupe Borja, Andrew N. N. Doust
Summary: Paysonia auriculata (Brassicaceae) seed oil is composed of multiple hydroxy fatty acids (HFAs), which show an initial low accumulation but a sharp increase after 21 days post-pollination. The gene expression network involved in HFA production is highly similar to that of Physaria fendleri, a related oil crop. Phylogenetic analysis suggests the evolution of the hydroxylase enzyme, FAH12, occurred once in Paysonia and Physaria, and is closely related to FAD2 enzymes.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Multidisciplinary Sciences
Emanuel Wyler, Kirstin Moesbauer, Vedran Franke, Asija Diag, Lina Theresa Gottula, Roberto Arsie, Filippos Klironomos, David Koppstein, Katja Hoenzke, Salah Ayoub, Christopher Buccitelli, Karen Hoffmann, Anja Richter, Ivano Legnini, Andranik Ivanov, Tommaso Mari, Simone Del Giudice, Jan Papies, Samantha Praktiknjo, Thomas F. Meyer, Marcel Alexander Mueller, Daniela Niemeyer, Andreas Hocke, Matthias Selbach, Altuna Akalin, Nikolaus Rajewsky, Christian Drosten, Markus Landthaler
Summary: Detailed analysis of SARS-CoV-2 infection in comparison with SARS-CoV reveals a stronger induction of innate immune response, including the upregulation of miRNA-155. Infected cells show broad upregulation of genes, while interferon beta/lambda genes and pro-inflammatory cytokines like IL-6 are expressed in only a small subset of cells. Time analysis suggests that interferon regulatory factors are activated before nuclear factor kappa B in response to infection, with heat shock protein 90 (HSP90) identified as a relevant protein for viral replication and inflammatory cytokine expression.
Article
Biochemistry & Molecular Biology
Negar Dinarvand, Farzaneh Karimi, Reza Azizi, Sedighe Rastaghi, Abdolkarim Sheikhi, Morteza Pourfarzam
Summary: This study aims to evaluate the expression of OCTN2 and its association with clinicopathological characteristics in breast cancer. The findings reveal that OCTN2 expression is significantly higher in breast cancer tissues compared to adjacent normal tissues. It is positively correlated with tumor size and Ki-67, and negatively correlated with the progesterone receptor (PR) status. OCTN2 expression may serve as a prognostic biomarker and a tumor oncogene, and a potential therapeutic target.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Dominik Hadzega, Gabriel Minarik, Marian Karaba, Katarina Kalavska, Juraj Benca, Sona Ciernikova, Tatiana Sedlackova, Petra Nemcova, Martin Bohac, Daniel Pindak, Lubos Klucar, Michal Mego
Summary: Recent research shows that breast tissues are not sterile and can harbor various species of microorganisms. Analysis of microbial composition in tumor tissue and normal breast tissue revealed differences between different breast cancer phenotypes. RNA sequencing highlighted variation in microbial composition between samples from Slovakia and China.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Wanfu Wu, Margaret Warner, Li Wang, Wei-Wei He, Ruipeng Zhao, Xiaoxiang Guan, Cindy Botero, Bo Huang, Charlotte Ion, Charles Coombes, Jan-Ake Gustafsson
Summary: Comparing gene expression profiles of malignant parts and normal adjacent parts of TNBC breasts revealed that CYP-mediated pathways may drive TNBC. However, despite being expressed in TNBC, ER13 is unlikely to be a tumor suppressor as its absence of main tethering partners renders it ineffective on genes related to proliferation and inflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Jia-Zih Dai, Yen-Ju Wang, Cheng-Hsun Chen, I-Lin Tsai, Yi-Chun Chao, Cheng-Wei Lin
Summary: Hormone dysregulation is considered a risk factor for obesity-mediated breast tumorigenesis. However, obesity is associated with poor outcomes among women diagnosed with hormone-independent breast cancer subtype called triple-negative breast cancer (TNBC). This study found that diet-induced obesity (DIO) facilitates tumorigenesis of TNBC cells. Mechanistically, DIO induces a metabolic addiction to fatty acid oxidation (FAO) and activates Yes-associated protein (YAP) signaling. YAP regulates mitochondrial redox homeostasis through transcriptional regulation of antioxidant-related enzymes, therefore protecting tumor cells from FAO-induced mitochondrial oxidative stress. Adipocytes-derived fatty acids are responsible for enhancing the FAO-YAP axis and antioxidative capacity. Additionally, higher expression of an obesity signature in breast cancer patients is positively correlated with YAP signaling and antioxidant genes. The findings reveal the crucial role of YAP in dictating mitochondrial redox homeostasis for obesity-mediated metabolic adaptation and breast tumor progression.
Article
Biochemistry & Molecular Biology
Nathaniel W. Snyder, James O'Brien, Bhupinder Singh, Gregory Buchan, Alejandro D. Arroyo, Xiaojing Liu, Anna Bostwick, Erika L. Varner, Anusha Angajala, Robert W. Sobol, Ian A. Blair, Clementina Mesaros, Stacy G. Wendell
Summary: This study investigated the metabolism of oxo-fatty acid products and found that mono-saturated oxo-fatty acids maintained their electrophilicity, while a secondary saturation resulted in a loss of electrophilicity. Prostaglandin reductase 1 (PTGR1) was found to play a critical role in the formation of mono-saturated metabolites of 15-oxoETE and 17-oxoDHA. Overexpression of PTGR1 increased the rate and total amount of oxo-fatty acid saturation in A549 cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Review
Chemistry, Medicinal
Pedro Barrios-Bernal, Zyanya Lucia Zatarain-Barron, Norma Hernandez-Pedro, Mario Orozco-Morales, Alejandra Olivera-Ramirez, Federico Avila-Moreno, Ana Laura Colin-Gonzalez, Andres F. Cardona, Rafael Rosell, Oscar Arrieta
Summary: Metformin has been studied as a potential anticancer agent for several years, and recent findings suggest that it may have efficacy in certain patient subgroups. However, there are still many unanswered questions regarding its mechanism of action and its effects in different patient populations.
Article
Medicine, Research & Experimental
Lin Zhang, Ming Fan, Francesco Napolitano, Xin Gao, Ying Xu, Lihua Li
Summary: Analyzing gene expression profiles between metastatic tumor tissues and control tissues revealed organ-specific metastasis genes and pathways. These genes and pathways interact with the molecular characteristics of cancer cells and target organs, influencing the metastasis process. Understanding organ-specific metastasis genes and pathways may identify potential drug targets and aid in the development of targeted treatment strategies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Chaojun Yan, Ronghui Gao, Chuan Gao, Kai Hong, Meng Cheng, Xiaojing Liu, Qing Zhang, Jing Zhang
Summary: Ferredoxin reductase (FDXR) has been shown to play a crucial role in promoting mitochondrial function and estrogen receptor positive (ER+) breast cancer. This study investigated the regulatory role of FDXR in fatty acid oxidation (FAO). The results demonstrated that depletion of FDXR inhibited FAO and reduced primary and endocrine-resistant breast cancer cell growth. Additionally, the combination of endocrine therapy and FAO inhibitor etomoxir showed synergistic inhibition of breast cancer cell growth.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Yiyao Jiang, Xu Zhang, Ting Wei, Xianjie Qi, Isah Amir Abba, Nana Zhang, Yao Chen, Ran Wang, Chao Shi
Summary: This study investigated the role of KDM5A in cardiac fibrosis and identified key genes associated with cardiac fibrosis through bioinformatics analysis. The findings have important implications for a better understanding of the mechanisms underlying cardiac fibrosis.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Medicine, Research & Experimental
Lin Zhu, Jianfeng Huang, Yi Wang, Zaiqing Yang, Xiaodong Chen
Summary: The study revealed the important role of chemerin in hepatic lipid metabolism, with its effects on lipid synthesis being mediated through GPR1. Free fatty acids and insulin were found to inhibit chemerin expression, while the key lipogenic transcription factor SREBP1c suppressed chemerin mRNA expression.
Article
Oncology
Shaojie Cheng, Xueying Wan, Liping Yang, Yilu Qin, Shanchun Chen, Yongcan Liu, Yan Sun, Yuxiang Qiu, Luyi Huang, Qizhong Qin, Xiaojiang Cui, Mingjun Wu, Manran Liu
Summary: RGCC overexpression is significantly associated with lung-specific metastasis of TNBC. RGCC activates AMPK alpha 2 and downstream signaling through RGCC-driven PLK1 activity to facilitate TNBC lung metastasis. The study provides implications for RGCC-driven oxidative phosphorylation and fatty acid oxidation as important therapeutic targets for TNBC treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Tamara Bintener, Maria Pires Pacheco, Demetra Philippidou, Christiane Margue, Ali Kishk, Greta Del Mistro, Luca Di Leo, Maria Moscardo Garcia, Rashi Halder, Lasse Sinkkonen, Daniela De Zio, Stephanie Kreis, Dagmar Kulms, Thomas Sauter
Summary: Despite high response rates to targeted kinase inhibitors, metastatic melanoma often relapses, calling for alternative therapies. This study used a refined workflow to predict common and melanoma-specific essential genes as potential drug targets. By reconstructing metabolic models, 28 candidate drugs were predicted and 12 showed high efficacy in vitro. Drug repurposing could expand treatment options for non-responders or those with acquired resistance to conventional melanoma treatments.
CELL DEATH & DISEASE
(2023)
Editorial Material
Oncology
Adrian L. Harris
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Simon R. Lord, Adrian L. Harris
Summary: Over the past 15 years, there has been extensive interest in repurposing the diabetes drug metformin as a cancer treatment. However, despite numerous large clinical trials in various tumor types, the results have been disappointing. This article summarizes the initial interest in metformin's potential in oncology, the current clinical program, and the lessons learned from this experience regarding further investigation of metformin in cancer.
BRITISH JOURNAL OF CANCER
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Patricia Sanchez-Perez, Ana Mata, May-Kristin Torp, Elia Lopez-Bernardo, Christina M. Heiestad, Jan M. Aronsen, Antonio Molina-Iracheta, Luis Jesus Jimenez-Borreguero, Pablo Garcia-Roves, Ana S. H. Costa, Christian Frezza, Michael P. Murphy, Kare-Olav Stenslokken, Susana Cadenas
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Alexander Hooftman, Christian G. Peace, Dylan G. Ryan, Emily A. Day, Ming Yang, Anne F. McGettrick, Maureen Yin, Erica N. Montano, Lihong Huo, Juliana E. Toller-Kawahisa, Vincent Zecchini, Tristram A. J. Ryan, Alfonso Bolado-Carrancio, Alva M. Casey, Hiran A. Prag, Ana S. H. Costa, Gabriela de los Santos, Mariko Ishimori, Daniel J. Wallace, Swamy Venuturupalli, Efterpi Nikitopoulou, Norma Frizzell, Cecilia Johansson, Alexander Von Kriegsheim, Michael P. Murphy, Caroline Jefferies, Christian Frezza, Luke A. J. O'Neill
Summary: Metabolic rewiring through an inflammatory aspartate-argininosuccinate shunt induces fumarate-mediated protein succination and inflammatory effects in macrophages. Inhibition of fumarate hydratase (FH) increases fumarate levels, suppresses mitochondrial respiration, and enhances interferon responses. FH inhibition may play a pathogenic role in systemic lupus erythematosus. These findings highlight the importance of FH in regulating macrophage functions and cytokine responses.
Article
Multidisciplinary Sciences
Vincent Zecchini, Vincent Paupe, Irene Herranz-Montoya, Joelle Janssen, Inge M. N. Wortel, Jordan L. Morris, Ashley Ferguson, Suvagata Roy Chowdury, Marc Segarra-Mondejar, Ana S. H. Costa, Goncalo C. Pereira, Laura Tronci, Timothy Young, Efterpi Nikitopoulou, Ming Yang, Dora Bihary, Federico Caicci, Shun Nagashima, Alyson Speed, Kalliopi Bokea, Zara Baig, Shamith Samarajiwa, Maxine Tran, Thomas Mitchell, Mark Johnson, Julien Prudent, Christian Frezza
Summary: The loss of FH in the kidney leads to early changes in mitochondrial morphology and the release of mtDNA into the cytosol, which activates the cGAS-STING-TBK1 pathway and induces an inflammatory response. This phenomenon is mediated by mitochondrial-derived vesicles and depends on SNX9. These findings demonstrate that increased levels of intracellular fumarate trigger a remodelling of the mitochondrial network and the generation of mitochondrial-derived vesicles, resulting in the release of mtDNA in the cytosol and the activation of the innate immune response.
Article
Endocrinology & Metabolism
Jonathan M. Gamwell, Keanu Paphiti, Leanne Hodson, Fredrik Karpe, Katherine E. Pinnick, Marijana Todorcevic
Summary: Differentiating human adipocytes in culture can be improved by modifying the protocol, such as reducing hormone exposure time, using physiological glucose concentration, and providing exogenous fatty acids. These modifications can restore impaired insulin signalling and glucose uptake, and enhance the functional aspects of adipocytes.
Article
Biochemistry & Molecular Biology
Yihe Wang, Astrid Hammer, Gerald Hoefler, Ernst Malle, Clare L. Hawkins, Christine Y. Chuang, Michael J. Davies
Summary: Atherosclerosis is a chronic inflammatory disease characterized by plaque formation in arterial walls. The study found that hypochlorous acid (HOCl) and chloramines can specifically modify aggrecan, a proteoglycan involved in atherogenesis. These modifications, different from those induced by ADAMTS1, can lead to irreversible protein cross-links. The findings also showed colocalization of aggrecan and HOCl-generated epitopes in advanced human atherosclerotic plaques.
Article
Biology
Georg Richtig, Melanie Kienzl, Sonja Rittchen, David Roula, Juergen Eberle, Zina Sarif, Martin Pichler, Gerald Hoefler, Akos Heinemann
Summary: This study aimed to investigate the pro-apoptotic effects of cannabinoids in metastatic melanoma and their value besides conventional targeted therapy. The results showed that cannabinoids can induce apoptosis through the mitochondrial cytochrome c release and caspase activation pathway, and do not interfere with commonly used targeted therapy.
Article
Endocrinology & Metabolism
Maria Elena Steidl, Elisa A. A. Nigro, Anne Kallehauge Nielsen, Roberto Pagliarini, Laura Cassina, Matteo Lampis, Christine Podrini, Marco Chiaravalli, Valeria Mannella, Gianfranco Distefano, Ming Yang, Mariam Aslanyan, Giovanna Musco, Ronald Roepman, Christian Frezza, Alessandra Boletta
Summary: Primary cilia respond to nutrient availability by adjusting their length through glutamine-mediated anaplerosis facilitated by asparagine synthetase (ASNS). Depriving cells of nutrients causes ciliary elongation, mediated by reduced mitochondrial function and ATP availability, independently of mTORC1. Cells lacking cilia show reduced glutamine-dependent mitochondrial anaplerosis during metabolic stress.
Editorial Material
Oncology
Nicole D. D. Machado, Lisa C. C. Heather, Adrian L. L. Harris, Geoff S. S. Higgins
Summary: The disappointing termination of clinical trials with potent complex I inhibitors, such as IACS-010759, has raised doubts about the justification for oxidative phosphorylation inhibitors and mitochondrial targeting strategies. Analyzing the potency, tissue selectivity, and toxicity of these agents can provide insights into the lessons learned from this failure and identify new opportunities.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Almudena Serrano-Benitez, Sophie E. Wells, Lylah Drummond-Clarke, Lilian C. Russo, John Christopher Thomas, Giovanna A. Leal, Mark Farrow, James Michael Edgerton, Shankar Balasubramanian, Ming Yang, Christian Frezza, Amit Gautam, Jan Brazina, Kamila Burdova, Nicolas C. Hoch, Stephen P. Jackson, Keith W. Caldecott
Summary: DNA single-strand breaks (SSBs) play a role in disrupting DNA replication and causing chromosome breakage. This study investigates whether SSBs induce chromosome breakage when located behind or ahead of replication forks, and finds that only SSBs ahead of replication forks trigger fork collapse and chromosome breakage. Furthermore, the study shows that CldU, a thymidine analogue, is cytotoxic to cells lacking SSB repair mechanisms and its incorporation in template DNA is particularly harmful during the following cell cycle. Additionally, BRCA-defective cells are highly sensitive to CldU, suggesting its potential clinical utility.
Article
Biochemistry & Molecular Biology
Patricia Sanchez-Perez, Ana Mata, May-Kristin Torp, Elia Lopez-Bernardo, Christina M. Heiestad, Jan Magnus Aronsen, Antonio Molina-Iracheta, Luis J. Jimenez-Borreguero, Pablo Garcia-Roves, Ana S. H. Costa, Christian Frezza, Michael P. Murphy, Kare-Olav Stenslokken, Susana Cadenas
Summary: Myocardial ischemia-reperfusion injury can lead to cardiomyocyte dysfunction, and mitochondria play a critical role in cardiomyocyte recovery. This study investigated the effects of UCP3 deficiency on functional, structural, and metabolic cardiac remodeling after IR. The results showed that UCP3 deficiency increases myocardial damage by promoting superoxide generation and mitochondrial structural changes.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Letter
Oncology
Tommaso Sconocchia, Johannes Fosselteder, Lisa Auinger, Erdem Oezkaya, Theresa Benezeder, Magdalena Lang, Christine Beham-Schmid, Gerald Hoefler, Armin Zebisch, Albert Woelfler, Heinz Sill, Peter Wolf, Herbert Strobl, Andreas Reinisch
Article
Clinical Neurology
Jakob V. E. Gerstl, Sarah E. Blitz, Qing Rui Qu, Alexander G. Yearley, Philipp Lassaren, Rebecca Lindberg, Saksham Gupta, Ari D. Kappel, Juan C. Vicenty-Padilla, Edoardo Gaude, Kunakorn C. Atchaneeyasakul, Shashvat M. Desai, Dileep R. Yavagal, Luca Peruzzotti-Jametti, Nirav J. Patel, Mohammed A. Aziz-Sultan, Rose Du, Timothy R. Smith, Joshua D. Bernstock
Summary: The global macroeconomic consequences of stroke in 2019 were significant, reaching $2059.67 billion or 1.66% of the global GDP. Central European, Eastern European, and Central Asian regions reported the highest economic losses due to stroke, while Southeast Asian, East Asian, and Oceanian regions had the highest economic losses due to intracerebral hemorrhage.
Article
Cell Biology
Connor Rogerson, Marco Sciacovelli, Lucas A. Maddalena, Andromachi Pouikli, Marc Segarra-Mondejar, Lorea Valcarcel-Jimenez, Christina Schmidt, Ming Yang, Elena Ivanova, Joshua Kent, Ariane Mora, Danya Cheeseman, Jason S. Carroll, Gavin Kelsey, Christian Frezza
Summary: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a cancer syndrome caused by inactivating germ-line mutations in fumarate hydratase (FH) and subsequent accumulation of fumarate. Fumarate accumulation leads to profound epigenetic changes and the activation of an antioxidant response via nuclear translocation of the transcription factor NRF2. The identification of FOXA2 as an antioxidant regulator provides additional insights into the molecular mechanisms behind cell responses to fumarate accumulation and potentially provides further avenues for therapeutic intervention for HLRCC.