Article
Biochemistry & Molecular Biology
Changyou Song, Bo Liu, Hongxia Li, Yongkai Tang, Xianping Ge, Bo Liu, Pao Xu
Summary: Dietary oxidized lipids are a major cause of excessive accumulation of reactive oxygen species (ROS), leading to oxidative stress. Emodin can alleviate oxidative stress by improving cellular morphology and function, maintaining a balance of metabolism and cell fate.
Review
Pharmacology & Pharmacy
Shohei Murakami, Yusuke Kusano, Keito Okazaki, Takaaki Akaike, Hozumi Motohashi
Summary: The KEAP1-NRF2 system plays a central role in cytoprotection by regulating antioxidant and detoxification genes, as well as possessing anti-inflammatory activity. It also participates in the regulation of cellular metabolism and mitochondrial function, particularly in relation to sulfur metabolism.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stefania Scicchitano, Maria Concetta Faniello, Maria Mesuraca
Summary: The human zinc finger protein 521 (ZNF521) plays a crucial role in the regulation of human ovarian cancer, affecting proliferation, progression, and cancer stem cell properties. This study also reveals the influence of ZNF521 on the NRF2-NOTCH signaling pathway in ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yudong Xia, Xiaoying Zhai, Yanning Qiu, Xuemei Lu, Yi Jiao
Summary: This review explores the complex interplay among Nrf2, oxidative stress, lipid metabolism, insulin signaling, and chronic inflammation in obesity, aiming to provide new insights for the treatment of obesity and its comorbidities.
Article
Gastroenterology & Hepatology
Valerio Azzimato, Ping Chen, Emelie Barreby, Cecilia Morgantini, Laura Levi, Ana Vankova, Jennifer Jager, Andre Sulen, Marina Diotallevi, Joanne X. Shen, Anne Miller, Ewa Ellis, Mikael Ryden, Erik Naslund, Anders Thorell, Volker M. Lauschke, Keith M. Channon, Mark J. Crabtree, Arvand Haschemi, Siobhan M. Craige, Mattia Mori, Francesco Spallotta, Myriam Aouadi
Summary: This study reveals a novel mechanism by which miR-144 inhibits NRF2 activity through the consumption of fumarate by activation of FH. By activating fumarate hydratase in the TCA cycle, hepatic miR-144 triggers an impaired antioxidant response in obesity.
Review
Biochemistry & Molecular Biology
Moon-Young Song, Da-Young Lee, Kyung-Soo Chun, Eun-Hee Kim
Summary: NRF2 and KEAP1 are crucial regulators of redox homeostasis, and their signaling pathway is associated with cancer cell proliferation and tumorigenesis. Modulating this pathway may serve as a novel therapeutic strategy for cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Haiyun Wang, Qiuling Huang, Jianhong Xia, Shan Cheng, Duanqing Pei, Xiaofei Zhang, Xiaodong Shu
Summary: MIB1 overexpression is detected in lung squamous carcinoma and adenocarcinoma and negatively correlates with patient survival. MIB1 induces EMT and cell migration through the Notch pathway, and degrades NRF2 in a Notch-independent manner, disrupting cellular antioxidant capacity.
MOLECULAR CANCER RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Xi Zhao, Xianglin Ji, Jin Qu, Kai Xie, Zixun Wang, Peilin Fang, Yuan Wang, Youyang Wan, Yang Yang, Wenjun Zhang, Peng Shi
Summary: RNA epigenetics is a new layer of mechanism to regulate gene expression. This study presents a molecule proximity-based technique for simultaneous analysis of multiple types of mRNA methylation with specific gene information in living cells. The technique utilizes a chip with vertically aligned diamond nanoneedles to access the intracellular domain and isolate the mRNAs while keeping the cells alive. The isolated RNAs are then encoded, amplified, and visualized to derive a quantitative measurement of the associated gene-specific m6A or m1A modifications. The study reveals the involvement of m6A and m1A in mRNA in cellular stress response and the rare occurrence of m6A and m1A dual methylation in a specific transcript.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Sean M. O'Cathail, Chieh-Hsi Wu, Rachael Thomas, Maria A. Hawkins, Tim S. Maughan, Annabelle Lewis
Summary: This study demonstrates that NRF2 plays a role in mediating radiation resistance in colorectal cancer, with potential therapeutic implications. By affecting metabolic pathways, NRF2 may improve radioresistance in rectal cancer patients and could be a target for therapeutic interventions.
Review
Biochemistry & Molecular Biology
Eleni Petsouki, Shara Natalia Sosa Cabrera, Elke H. Heiss
Summary: AMPK and NRF2 are key regulatory factors in cellular energy homeostasis and stress response, and they may interact and cooperate to readjust cellular homeostasis at the molecular level.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Noemi Esteras, Thomas S. Blacker, Evgeny A. Zherebtsov, Olga A. Stelmashuk, Ying Zhang, W. Christian Wigley, Michael R. Duchen, Albena T. Dinkova-Kostova, Andrey Y. Abramov
Summary: The transcription factor Nrf2 and its repressor Keap1 play a crucial role in cell stress adaptation by regulating gene expression related to cellular detoxification, antioxidant defense, and energy metabolism. This study investigated the impact of Nrf2 on glucose distribution and the connection between NADH production in energy metabolism and NADPH homeostasis using glio-neuronal cultures. The findings showed that Nrf2 activation enhances glucose uptake in neurons and astrocytes, with prioritized consumption for mitochondria-related energy production rather than NADPH synthesis in the pentose phosphate pathway.
Article
Oncology
Yang Liu, Fu-Ju Chou, Fengchao Lang, Meili Zhang, Hua Song, Wei Zhang, Dionne L. Davis, Nicole J. Briceno, Yang Zhang, Patrick J. Cimino, Kareem A. Zaghloul, Mark R. Gilbert, Terri S. Armstrong, Chunzhang Yang
Summary: This study reveals that mutations of the IDH gene are common in human malignancies and play critical roles in malignant transformation. The PI3K/AKT signaling pathway is enhanced in IDH-mutated cancer cells. Combining the AKT inhibitor Ipa with the genotoxic agent TMZ shows synergistic therapeutic effect in IDH-mutated cancer cells.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Tereza Koranova, Lukas Dvoracek, Dana Grebenova, Pavla Roselova, Adam Obr, Katerina Kuzelova
Summary: Inhibiting or deleting members of the P21-activated kinases (PAKs) family can impact cell metabolism, influencing mitochondrial respiration and aerobic glycolysis rates. Specifically, downregulation of PAK2 is linked to oxidative phosphorylation, while knockout of PAK1 results in increased glycolysis. Despite these changes, the overall metabolic capacity is not substantially reduced, possibly due to redundancy or compensatory mechanisms within the PAK1/PAK2 regulatory roles.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Cell Biology
Sachin Verma, David Crawford, Ali Khateb, Yongmei Feng, Eduard Sergienko, Gaurav Pathria, Chen-Ting Ma, Steven H. Olson, David Scott, Rabi Murad, Eytan Ruppin, Michael Jackson, Ze'ev A. Ronai
Summary: This study demonstrates the dependence of melanoma on the mitochondrial protein GCDH for cell survival and tumor growth. Inhibiting the GCDH pathway through NRF2 glutarylation leads to cell death and suppression of melanoma growth.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sanjit K. Dhar, Timothy Scott, Chi Wang, Teresa W. M. Fan, Daret K. St Clair
Summary: This study reveals the regulatory role of mitochondrial-generated superoxide radicals in gene expression and establishes a new paradigm that recognizes O2· as an initiator of metabolic reprogramming and epigenetic regulation in response to mitochondrial dysfunction.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Critical Care Medicine
Margot DeBot, Christopher Erickson, Marguerite Kelher, Terry R. Schaid, Ernest E. Moore, Angela Sauaia, Alexis Cralley, Ian LaCroix, Angelo D'Alessandro, Kirk Hansen, Mitchell J. Cohen, Christopher C. Silliman, Julia Coleman
Summary: By studying the sex differences in platelets and cryoprecipitate coagulation factors, it was found that blood products from female donors are more effective in improving coagulation dysfunction compared to male blood products. Additionally, female-donor cryoprecipitate contains more factor V and factor XIII, and several proteins with potential immunological significance. These sex differences may influence how transfusions modulate thromboinflammation caused by trauma, suggesting the potential role of sex-specific transfusion guidelines in hemostatic resuscitation.
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2023)
Article
Critical Care Medicine
Terry R. Schaid, Ian LaCroix, Kirk C. Hansen, Angelo D'Alessandro, Ernest E. Moore, Angela Sauaia, Monika Dzieciatkowska, Margot DeBot, Alexis L. Cralley, Otto Thielen, William Hallas, Christopher Erickson, Sanchayita Mitra, Anirban Banerjee, Kenneth Jones, Christopher C. Silliman, Mitchell J. Cohen
Summary: This study identified the proteomic signature of trauma-induced NETosis and revealed that NETosis may mediate organ dysfunction following severe injury. SerpinB1 was identified as a major component of this NET protein profile and could serve as an early marker of excessive NETosis after injury.
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2023)
Article
Hematology
Angelo D'Alessandro, S. Mehdi Nouraie, Yingze Zhang, Francesca Cendali, Fabia Gamboni, Julie A. Reisz, Xu Zhang, Kyle W. Bartsch, Matthew D. Galbraith, Victor R. Gordeuk, Mark T. Gladwin
Summary: This study evaluates the red blood cell metabolism of 587 sickle cell disease patients and finds significant metabolic alterations in RBC acylcarnitines, pyruvate, sphingosine 1-phosphate, creatinine, kynurenine, and urate in Hb SS genotype compared to AA and SC RBCs. Surprisingly, the metabolism of SC RBCs is dramatically different from SS RBCs, with all glycolytic intermediates significantly elevated. These findings provide insights into the metabolic signatures and potential underlying mechanisms in sickle cell disease.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ji Young Lee, Reece P. Stevens, Viktoriya V. Pastukh, Viktor M. Pastukh, Natalya Kozhukhar, Mikhail F. Alexeyev, Julie A. Reisz, David Nerguizian, Angelo D'Alessandro, Anna Koloteva, Meredith S. Gwin, Justin T. Roberts, Glen M. Borchert, Brant M. Wagener, Jean-Franc Comma Ois Pittet, Brian B. Graham, Kurt R. Stenmark, Troy Stevens
Summary: Pulmonary microvascular endothelial cells prefer glucose over fructose for glycolysis, and this study found that the enzyme PFKFB3 inhibits fructose metabolism in these cells. PFKFB3 knockout led to increased survival and enhanced fructose utilization in fructose-rich medium. The study also demonstrated that pneumonia is associated with increased fructose levels in the lung. These findings suggest that PFKFB3 is a key regulator of glucose versus fructose use in glycolysis in pulmonary microvascular endothelial cells.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Oncology
Miles Piper, Maureen Hoen, Laurel B. Darragh, Michael W. Knitz, Diemmy Nguyen, Jacob Gadwa, Greta Durini, Idil Karakoc, Abby Grier, Brooke Neupert, Benjamin Van Court, Khalid N. M. Abdelazeem, Justin Yu, Nicholas A. Olimpo, Sophia Corbo, Richard Blake Ross, Tiffany T. Pham, Molishree Joshi, Ross M. Kedl, Anthony J. Saviola, Maria Amann, Pablo Umana, Laura Codarri Deak, Christian Klein, Angelo D'Alessandro, Sana D. Karam
Summary: In PDAC patients, the response to RT involves changes in IL-2Rb, IL-2Rg, and IL-2Ra expression. PD1-IL2v, a PD-1-targeted IL-2 variant immunocytokine, enhances tumor-specific T cell activation and reduces Treg suppression. In PDAC mouse models, PD1-IL2v treatment improves survival, increases tumor-infiltrating CD8+ T cells, and activates antigen-specific CD8+ T cells, especially when combined with single-dose RT.
Article
Biochemistry & Molecular Biology
Giulia Unali, Giovanni Crivicich, Isabel Pagani, Monah Abou-Alezz, Filippo Folchini, Erika Valeri, Vittoria Matafora, Julie A. Reisz, Anna Maria Sole Giordano, Ivan Cuccovillo, Giacomo M. Butta, Lorena Donnici, Angelo D'Alessandro, Raffaele De Francesco, Lara Manganaro, Davide Cittaro, Ivan Merelli, Carolina Petrillo, Angela Bachi, Elisa Vicenzi, Anna Kajaste-Rudnitski
Summary: The interferon-induced transmembrane proteins (IFITM) inhibit endocytic viral entry by binding to phosphatidylinositol 3,4,5-trisphosphate (PIP3), which plays a key role in endosomal antiviral immunity. The level of PIP3 is closely correlated with the potency of endosomal IFITM restriction, and exogenous PIP3 enhances the inhibition of endocytic viruses. These findings elucidate cell-compartment-specific antiviral mechanisms and have potential relevance for the development of broadly acting antiviral strategies.
Article
Biochemistry & Molecular Biology
Sachin Kumar, Jeffrey D. Vassallo, Kalpana J. Nattamai, Aishlin Hassan, Rebekah Karns, Angelika Vollmer, Karin Soller, Vadim Sakk, Mehmet Sacma, Travis Nemkov, Angelo D'Alessandro, Hartmut Geiger
Summary: It has been found that culturing hematopoietic stem cells (HSCs) at a pH of 6.9 for 2 days can maintain their potential, unlike cultivation at the commonly used pH of 7.4. These HSCs maintained at pH 6.9 exhibit smaller size, lower metabolic activity, weaker proliferation, and enhanced reconstitution ability upon transplantation compared to those cultivated at pH 7.4. This is due to the attenuation of the polyamine pathway in HSCs cultured at pH 6.9. Inhibiting the polyamine pathway in HSCs cultured at pH 7.4 with DFMO mimics the phenotypes and potential of HSCs cultured at pH 6.9. Exposing HSCs to a pH of 6.9 ex vivo positively regulates their function by reducing polyamines. These findings have the potential to improve short-term cultivation protocols for HSC transplantation and gene therapy interventions.
Article
Biochemistry & Molecular Biology
Michele Aventaggiato, Adele Preziosi, Hossein Cheraghi Bidsorkhi, Emily Schifano, Simone Vespa, Stefania Mardente, Alessandra Zicari, Daniela Uccelletti, Patrizia Mancini, Lavinia Vittoria Lotti, Maria Sabrina Sarto, Marco Tafani
Summary: Nanomaterials, particularly zinc oxide (ZnO) nanostructures, are being widely studied in medicine due to their unique properties. However, recent research has shown that ZnO nanoparticles (ZnO-NPs) and ZnO nanorods (ZnO-NRs) can induce cellular toxicity. This study aimed to investigate the effects of ZnO-NR treatment on normal and cancer cells. The results demonstrated that ZnO-NR treatments led to cell death, activation of hypoxia response, and induction of autophagy and mitophagy. While ZnO-NRs showed potential in reducing cancer growth, concerns were raised regarding their impact on normal cells in the long term.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jacqueline A. Turner, Malia A. Fredrickson, Marc D'Antonio, Elizabeth Katsnelson, Morgan MacBeth, Robert Van Gulick, Tugs-Saikhan Chimed, Martin McCarter, Angelo D'Alessandro, William A. Robinson, Kasey L. Couts, Roberta Pelanda, Jared Klarquist, Richard P. Tobin, Raul M. Torres
Summary: Lysophosphatidic acid (LPA) increases in concentration in various cancer types and has an impact on CD8 T cell metabolism, phenotype, and effector functions. Plasma concentrations of LPA can predict the response to immunotherapy.
NATURE COMMUNICATIONS
(2023)
Article
Physiology
Francesca I. Cendali, Travis Nemkov, Christina Lisk, Ian S. Lacroix, Seyed-Mehdi Nouraie, Yingze Zhang, Victor R. Gordeuk, Paul W. Buehler, David Irwin, Angelo D'Alessandro
Summary: This study investigated the exercise intolerance and metabolic changes in sickle cell disease patients using a mouse model and clinical cases. The results identified specific metabolites, including carboxylic acids, sphingosine 1-phosphate, and acylcarnitine, that were associated with reduced exercise tolerance in both mouse models and patients. These findings have important implications for understanding the mechanisms of exercise intolerance and developing preventive and therapeutic strategies for sickle cell disease.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Emily Schifano, Gianluca Cavoto, Francesco Pandolfi, Giorgio Pettinari, Alice Apponi, Alessandro Ruocco, Daniela Uccelletti, Ilaria Rago
Summary: The emergence of multidrug-resistant bacteria is a growing threat to public health, necessitating the development of non-antibiotic antibacterial approaches. In this study, vertically aligned carbon nanotubes (VA-CNTs) with controlled nanomorphology were proposed as effective platforms for bacteria eradication. Through a combination of microscopic and spectroscopic techniques, the topography of VA-CNTs was tailored in a controlled and time-efficient manner using plasma etching processes. The highest reduction in cell viability was observed for VA-CNTs modified using plasma etching with Ar and O-2, indicating their potential as a surface for inactivating both planktonic and biofilm infections.
Article
Endocrinology & Metabolism
Shanlee M. Davis, Rhianna Urban, Angelo D'Alessandro, Julie A. Reisz, Christine L. Chan, Megan Kelsey, Susan Howell, Nicole Tartaglia, Philip Zeitler, Peter Baker Ii
Summary: Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown. This study found that the plasma metabolome profile in adolescent males with KS is distinctly different from that in males without KS, suggesting differences in mitochondrial β-oxidation.
ENDOCRINE CONNECTIONS
(2023)
Article
Developmental Biology
Hiroko Kawakami, Katherine Q. Chen, Ruizhi Zhang, Matthew P. Pappas, Abigail Bailey, Julie A. Reisz, Dylan Corcoran, Ryuichi Nishinakamura, Angelo D'Alessandro, Yasuhiko Kawakami
Summary: Recent studies have shown that regulation of cellular metabolism, especially glycolysis and pathways branching from glycolysis, plays a crucial role in vertebrate embryo development. The transcription factor Sall4 is highly expressed in undifferentiated cells in developing mouse embryos and is involved in the regulation of glycolytic metabolism. Knockout experiments demonstrate that Sall4 restricts glycolysis in limb buds and is important for hindlimb patterning.
DEVELOPMENTAL BIOLOGY
(2023)
Article
Nutrition & Dietetics
Christopher Y. Kim, Hannah J. Larsen, Steven L. Spitalnik, Eldad A. Hod, Richard O. Francis, Krystalyn E. Hudson, Dominique E. Gordy, Elizabeth F. Stone, Sandy Peltier, Pascal Amireault, Angelo D'Alessandro, James C. Zimring, Paul W. Buehler, Xiaoyun Fu, Tiffany Thomas
Summary: High-dose fish oil intake reduces the quality of red blood cells, while low-dose fish oil improves the filterability of fresh red blood cells and reduces lipid peroxidation of stored red blood cells. However, low-dose fish oil does not improve the post-transfusion recovery capacity of stored red blood cells.
Article
Humanities, Multidisciplinary
Monia Vadrucci, Cristina Cicero, Claudia Mazzuca, Leonardo Severini, Daniela Uccelletti, Emily Schifano, Fulvio Mercuri, Ugo Zammit, Noemi Orazi, Francesco D'Amico, Pietro Parisse
Summary: This study evaluated the effect of X-ray irradiation as a disinfection treatment on original ancient parchment samples from a discarded book cover. Bacterial and fungal species from the book cover were characterized and irradiated with increasing doses of X-rays to assess the effectiveness of the antimicrobial protocol. Various techniques were employed to test the deterioration effects of X-ray treatment and natural aging on the collagen matrix of the parchment sample. The results indicate that the X-rays-based disinfection treatment has limited effects on the collagen support, highlighting its potential for mass disinfection of library and archival materials.