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1
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Carter L, Nightingale A, Feelisch M, Niu X. A Droplet Microfluidic Sensor for Point-of-Care Measurement of Plasma/Serum Total Free Thiol Concentrations. Anal Chem 2025; 97:2678-2688. [PMID: 39868883 PMCID: PMC11822743 DOI: 10.1021/acs.analchem.4c04163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 01/05/2025] [Accepted: 01/07/2025] [Indexed: 01/28/2025]
Abstract
Total free thiols are an important marker of the whole-body redox state, which has been shown to be associated with clinical outcome in health and disease. Recent investigations have suggested that increased insight may be gained by monitoring alterations of redox state in response to exercise and hypoxia and to monitor redox trajectories in disease settings. However, conducting such studies is challenging due to the requirement for repeated venous blood sampling and intensive lab work. Droplet microfluidic sensors offer an alternative platform for developing a point-of-care testing approach using small sample volumes and automated systems to complement or ultimately replace laboratory testing. Here we developed a small, portable droplet microfluidic sensor that can measure total free thiol concentrations in 20 μL human plasma (or serum) samples, providing a reading in less than 10 min. This system features a novel method to enhance the mixing of reagent and analyte in droplets containing viscous biological fluids. The results in a range of real-world human plasma samples showed equivalence with current standard laboratory assays while reducing sample volume requirements 9-fold and fully automating the process. Micro hematocrit capillaries allowed testing of capillary blood samples collected by fingerprick lancing. The system was used to monitor total free thiols using fingerprick samples in healthy volunteers and revealed significant changes in total free thiols in response to food intake and exercise. This device has the potential to improve our ability to conduct physiological studies of total free thiol level changes and improve our understanding of redox physiology, which may ultimately be applied in redox medicine to improve patient care.
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Affiliation(s)
- Liam Carter
- Mechanical
Engineering, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
| | - Adrian Nightingale
- Mechanical
Engineering, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
| | - Martin Feelisch
- Perioperative
and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, U.K.
- Clinical
& Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, U.K.
| | - Xize Niu
- Mechanical
Engineering, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
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2
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He L, Wei X, Zhang W, Xu N, Wu J, Yu F, Liu H. Fabrication of a Redox-Reversible Near-Infrared Fluorogenic Probe for Ferroptosis Process Monitoring and the Early Diagnosis of Diabetes. Anal Chem 2025; 97:2411-2417. [PMID: 39838582 DOI: 10.1021/acs.analchem.4c05927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
Ferroptosis is a type of cell death triggered by the iron-dependent accumulation of lipid peroxides in cells. Diabetes, a chronic metabolic disorder characterized by hyperglycemia, can lead to various health complications. The process of ferroptosis and the progression of diabetes are closely linked to redox homeostasis, which is regulated by the levels of reactive oxygen and sulfur species. Currently, there are no fluorescent probes available to monitor changes in redox homeostasis during ferroptosis and diabetes. Here, we report the first endeavor to create a reversible near-infrared fluorogenic (NIRF) probe for monitoring the process of ferroptosis reversal and precise diabetes diagnosis. In vitro data demonstrated that NIR-CSTe could cyclically and reversibly detect ONOO- and GSH up to four times with minimal loss in fluorescence intensity. With the help of NIR-CSTe, we observed that HT-1080 cells, induced to undergo ferroptosis by erastin after being washed with PBS for 24 h and then treated with ferrostatin-1, showed a recovery in intracellular GSH levels. In contrast, treatment with deferoxamine did not yield similar results. Lastly, NIR-CSTe was also utilized for the early diagnosis and efficacy assessment of diabetes in relation to ONOO-/GSH redox balance, with results illustrating that the combined administration of metformin and empagliflozin was more effective than using either drug alone. Thus, this smart probe holds significant potential as an essential tool for clinical diagnosis and treatment of diseases associated with redox homeostasis.
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Affiliation(s)
- Lingchao He
- Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Radiotherapy, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
- Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China
| | - Xiao Wei
- Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China
| | - Wei Zhang
- Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Radiotherapy, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
- Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China
| | - Ningge Xu
- Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China
| | - Jinsheng Wu
- Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Radiotherapy, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
| | - Fabiao Yu
- Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Radiotherapy, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
- Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China
| | - Heng Liu
- Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Radiotherapy, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
- Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China
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3
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Zhang S, Wang N, Gao Z, Gao J, Wang X, Xie H, Wang CY, Zhang S. Reductive stress: The key pathway in metabolic disorders induced by overnutrition. J Adv Res 2025:S2090-1232(25)00031-1. [PMID: 39805424 DOI: 10.1016/j.jare.2025.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 12/04/2024] [Accepted: 01/05/2025] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND The balance of redox states is crucial for maintaining physiological homeostasis. For decades, the focus has been mainly on the concept of oxidative stress, which is involved in the mechanism of almost all diseases. However, robust evidence has highlighted that reductive stress, the other side of the redox spectrum, plays a pivotal role in the development of various diseases, particularly those related to metabolism and cardiovascular health. AIM OF REVIEW In this review, we present an extensive array of evidence for the occurrence of reductive stress and its significant implications mainly in metabolic and cardiovascular diseases. KEY SCIENTIFIC CONCEPTS OF REVIEW Reductive stress is defined as a shift in the cellular redox balance towards a more reduced state, characterized by an excess of endogenous reductants (such as NADH, NADPH, and GSH) over their oxidized counterparts (NAD+, NADP+, and GSSG). While oxidative stress has been the predominant mechanism studied in obesity, metabolic disorders, and cardiovascular diseases, growing evidence underscores the critical role of reductive stress. This review discusses how reductive stress contributes to metabolic and cardiovascular pathologies, emphasizing its effects on key cellular processes. For example, excessive NADH accumulation can disrupt mitochondrial function by impairing the electron transport chain, leading to decreased ATP production and increased production of reactive oxygen species. In the endoplasmic reticulum (ER), an excess of reductive equivalents hampers protein folding, triggering ER stress and activating the unfolded protein response, which can lead to insulin resistance and compromised cellular homeostasis. Furthermore, we explore how excessive antioxidant supplementation can exacerbate reductive stress by further shifting the redox balance, potentially undermining the beneficial effects of exercise, impairing cardiovascular health, and aggravating metabolic disorders, particularly in obese individuals. This growing body of evidence calls for a reevaluation of the role of reductive stress in disease pathogenesis and therapeutic interventions.
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Affiliation(s)
- Shiyi Zhang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Na Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhichao Gao
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Gao
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohui Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hao Xie
- Institute of Translational Medicine, Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
| | - Cong-Yi Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Shu Zhang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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4
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Louati K, Maalej A, Kolsi F, Kallel R, Gdoura Y, Borni M, Hakim LS, Zribi R, Choura S, Sayadi S, Chamkha M, Mnif B, Khemakhem Z, Boudawara TS, Boudawara MZ, Bouraoui A, Kraiem J, Safta F. A Shotgun Proteomic-Based Approach with a Q-Exactive Hybrid Quadrupole-Orbitrap High-Resolution Mass Spectrometer for the Assessment of Pesticide Mixture-Induced Neurotoxicity on a 3D-Developed Neurospheroid Model from Human Brain Meningiomas: Identification of Trityl-Post-Translational Modification. J Proteome Res 2024; 23:5554-5576. [PMID: 39556108 PMCID: PMC11629387 DOI: 10.1021/acs.jproteome.4c00804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/14/2024] [Accepted: 10/31/2024] [Indexed: 11/19/2024]
Abstract
The widespread use of pesticides, particularly in combinations, has resulted in enhanced hazardous health effects. However, little is known about their molecular mechanism of interactions. The aim of this study was to assess the neurotoxicity effect of pesticides in mixtures by adopting a 3D in vitro developed neurospheroid model, followed by treatment by increased concentrations of pesticides for 24 h and analysis by a shotgun proteomic-based approach with high-resolution tandem mass spectrometry. Three proteins, namely, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), α-enolase, and phosphoglycerate-kinase-1, were selected as key targets in the metabolic process. Only high doses of pesticides mitigated cell-density proliferation with the occurrence of apoptotic cells, which unlikely makes any neurological alterations in environmental regulatory exposures. The proteomic analysis showed that majority of altered proteins were implicated in cell metabolism. De novo peptide sequencing revealed ion losses and adduct formation, namely, a trityl-post-translational modification in the active site of 201-GAPDH protein. The study also highlights the plausible role of pyrethroids to be implicated in the deleterious effects of pesticides in a mixture. To the best of our knowledge, our finding is the first in toxicoproteomics to deeply elucidate pesticides' molecular interactions and their ability to adduct proteins as a pivotal role in the neurotoxicity mechanism.
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Affiliation(s)
- Kaouthar Louati
- Laboratory
of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia
| | - Amina Maalej
- Laboratory
of Environmental Bioprocesses, Centre of
Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177 , 3018Sfax, Tunisia
| | - Fatma Kolsi
- Department
of Neurosurgery, Habib Bourguiba University
Hospital, Road El Ain
km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Rim Kallel
- Laboratory
of Pathological Anatomy and Cytology, Habib
Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Yassine Gdoura
- Department
of Neurosurgery, Habib Bourguiba University
Hospital, Road El Ain
km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Mahdi Borni
- Department
of Neurosurgery, Habib Bourguiba University
Hospital, Road El Ain
km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Leila Sellami Hakim
- Laboratory
of Pathological Anatomy and Cytology, Habib
Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia
| | - Rania Zribi
- Faculty
of Letters and Humanities, University of
Sfax, Airport Road, Km
4.5, 3023 Sfax, Tunisia
| | - Sirine Choura
- Laboratory
of Environmental Bioprocesses, Centre of
Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177 , 3018Sfax, Tunisia
| | - Sami Sayadi
- Biotechnology
Program, Center for Sustainable Development, College of Arts and Sciences, Qatar University, 2713 Doha, Qatar
| | - Mohamed Chamkha
- Laboratory
of Environmental Bioprocesses, Centre of
Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177 , 3018Sfax, Tunisia
| | - Basma Mnif
- Department
of Bacteriology, Habib Bourguiba University
Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Zouheir Khemakhem
- Legal
Medicine
Department, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Tahya Sellami Boudawara
- Laboratory
of Pathological Anatomy and Cytology, Habib
Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Mohamed Zaher Boudawara
- Department
of Neurosurgery, Habib Bourguiba University
Hospital, Road El Ain
km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia
- Faculty
of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia
| | - Abderrahman Bouraoui
- Laboratory
of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia
| | - Jamil Kraiem
- Laboratory
of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia
| | - Fathi Safta
- Laboratory
of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia
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5
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Gallero S, Persson KW, Henríquez-Olguín C. Unresolved questions in the regulation of skeletal muscle insulin action by reactive oxygen species. FEBS Lett 2024; 598:2145-2159. [PMID: 38803005 DOI: 10.1002/1873-3468.14937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 04/10/2024] [Accepted: 04/22/2024] [Indexed: 05/29/2024]
Abstract
Reactive oxygen species (ROS) are well-established signaling molecules implicated in a wide range of cellular processes, including both oxidative stress and intracellular redox signaling. In the context of insulin action within its target tissues, ROS have been reported to exert both positive and negative regulatory effects. However, the precise molecular mechanisms underlying this duality remain unclear. This Review examines the complex role of ROS in insulin action, with a particular focus on skeletal muscle. We aim to address three critical aspects: (a) the proposed intracellular pro-oxidative redox shift elicited by insulin, (b) the evidence supporting that redox-sensitive cysteine modifications impact insulin signaling and action, and (c) cellular mechanisms underlying how ROS can paradoxically act as both enhancers and inhibitors of insulin action. This Review underscores the urgent need for more systematic research to identify specific reactive species, redox targets, and the physiological significance of redox signaling in maintaining insulin action and metabolic health, with a particular emphasis on human skeletal muscle.
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Affiliation(s)
- Samantha Gallero
- The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark
| | - Kaspar W Persson
- The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark
| | - Carlos Henríquez-Olguín
- The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark
- Exercise Science Laboratory, Faculty of Medicine, Universidad Finis Terrae, Santiago, Chile
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6
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Kuramochi T, Yamashita Y, Arai K, Kanemura S, Muraoka T, Okumura M. Boosting the enzymatic activity of CxxC motif-containing PDI family members. Chem Commun (Camb) 2024; 60:6134-6137. [PMID: 38829522 DOI: 10.1039/d4cc01712a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of members of the protein disulphide isomerase (PDI) family and thus can be used to accelerate folding processes and increase the production of native proteins by minimal loading in comparison to glutathione.
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Affiliation(s)
- Tsubura Kuramochi
- Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
- Department of Molecular and Chemical Life Sciences, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi, 980-8577, Japan
| | - Yukino Yamashita
- Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
| | - Kenta Arai
- Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan
- Institute of Advanced Biosciences, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan
| | - Shingo Kanemura
- Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
| | - Takahiro Muraoka
- Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
- Kanagawa Institute of Industrial Science and Technology, 3-2-1 Sakato, Takatsu-ku, Kawasaki, Kanagawa 213-0012, Japan
| | - Masaki Okumura
- Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
- Department of Molecular and Chemical Life Sciences, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi, 980-8577, Japan
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7
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Hara Y, Yoshizawa K, Yaguchi A, Hiramatsu H, Uchida N, Muraoka T. ROS-Responsive Methionine-Containing Amphiphilic Peptides Impart Enzyme-Triggered Phase Transition and Antioxidant Cell Protection. Biomacromolecules 2024; 25:3499-3506. [PMID: 38720562 PMCID: PMC11170935 DOI: 10.1021/acs.biomac.4c00129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 06/11/2024]
Abstract
Reactive oxygen species (ROS) are produced by cellular activities, such as metabolism and immune response, and play important roles in cell signaling and homeostasis. However, overproduced ROS causes irreversible damage to nucleic acids and membrane lipids, supporting genetic mutations and enhancing the effects of aging. Cells defend themselves against ROS using antioxidant systems based on redox-active sulfur and transition metals. Inspired by such biological redox-responsive systems, we developed methionine-containing self-assembling peptides. The Met-containing peptides formed hydrogels that underwent a gel-to-sol phase transition upon oxidation by H2O2, and the sensitivity of the peptides to the oxidant increased as the number of Met residues increased. The peptide containing three Met residues, the largest number of Met residues in our series of designed peptides, showed the highest sensitivity to oxidation and detoxification to protect cells from ROS damage. In addition, this peptide underwent a phase transition in response to H2O2 produced by an oxidizing enzyme. This study demonstrates the design of a supramolecular biomaterial that is responsive to enzymatically generated ROS and can protect cells against oxidative stress.
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Affiliation(s)
- Yoshika Hara
- Department
of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei 184-8588, Tokyo, Japan
| | - Ken Yoshizawa
- Department
of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei 184-8588, Tokyo, Japan
| | - Atsuya Yaguchi
- Department
of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei 184-8588, Tokyo, Japan
| | - Hirotsugu Hiramatsu
- Department
of Applied Chemistry and Institute of Molecular Science National Yang Ming Chiao Tung University, 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan
- Center
for Emergent Functional Matter Science National
Yang Ming Chiao Tung University 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan
| | - Noriyuki Uchida
- Department
of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei 184-8588, Tokyo, Japan
| | - Takahiro Muraoka
- Department
of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei 184-8588, Tokyo, Japan
- Kanagawa
Institute of Industrial Science and Technology, 705-1 Shimoimaizumi, Ebina 243-0435, Kanagawa, Japan
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8
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Huang S, Zhang W, Xuan S, Si H, Huang D, Ba M, Qi D, Pei X, Lu D, Li Z. Chronic sleep deprivation impairs retinal circadian transcriptome and visual function. Exp Eye Res 2024; 243:109907. [PMID: 38649019 DOI: 10.1016/j.exer.2024.109907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/07/2024] [Accepted: 04/18/2024] [Indexed: 04/25/2024]
Abstract
Sleep loss is common in modern society and is increasingly associated with eye diseases. However, the precise effects of sleep loss on retinal structure and function, particularly on the retinal circadian system, remain largely unexplored. This study investigates these effects using a chronic sleep deprivation (CSD) model in mice. Our investigation reveals that CSD significantly alters the retinal circadian transcriptome, leading to remarkable changes in the temporal patterns of enriched pathways. This perturbation extends to metabolic and immune-related transcriptomes, coupled with an accumulation of reactive oxygen species in the retina. Notably, CSD rhythmically affects the thickness of the ganglion cell complex, along with diurnal shifts in microglial migration and morphology within the retina. Most critically, we observe a marked decrease in both scotopic and photopic retinal function under CSD conditions. These findings underscore the broad impact of sleep deprivation on retinal health, highlighting its role in altering circadian gene expression, metabolism, immune response, and structural integrity. Our study provides new insights into the broader impact of sleep loss on retinal health.
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Affiliation(s)
- Shenzhen Huang
- Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Zhengzhou, China; Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China
| | - Wenxiao Zhang
- Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China
| | - Shuting Xuan
- Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Hongli Si
- Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China
| | - Duliurui Huang
- Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China
| | - Mengru Ba
- Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China
| | - Di Qi
- Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaoting Pei
- Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Dingli Lu
- Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhijie Li
- Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Zhengzhou, China; Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
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9
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Epel B, Kao JPY, Eaton SS, Eaton GR, Halpern HJ. Direct Measurement and Imaging of Redox Status with Electron Paramagnetic Resonance. Antioxid Redox Signal 2024; 40:850-862. [PMID: 36680741 PMCID: PMC11386996 DOI: 10.1089/ars.2022.0216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Significance: Fundamental to the application of tissue redox status to human health is the quantification and localization of tissue redox abnormalities and oxidative stress and their correlation with the severity and local extent of disease to inform therapy. The centrality of the low-molecular-weight thiol, glutathione, in physiological redox balance has long been appreciated, but direct measurement of tissue thiol status in vivo has not been possible hitherto. Recent advances in instrumentation and molecular probes suggest the feasibility of real-time redox assessment in humans. Recent Advances: Recent studies have demonstrated the feasibility of using low-frequency electron paramagnetic resonance (EPR) techniques for quantitative imaging of redox status in mammalian tissues in vivo. Rapid-scan (RS) EPR spectroscopy and imaging, new disulfide-dinitroxide spin probes, and novel analytic techniques have led to significant advances in direct, quantitative imaging of thiol redox status. Critical Issues: While novel RS EPR imaging coupled with first-generation molecular probes has demonstrated the feasibility of imaging thiol redox status in vivo, further technical advancements are desirable and ongoing. These include developing spin probes that are tailored for specific tissues with response kinetics tuned to the physiological environment. Equally critical are RS instrumentation with higher signal-to-noise ratio and minimal signal distortion, as well as optimized imaging protocols for image acquisition with sparsity adapted to image information content. Future Directions: Quantitative images of tissue glutathione promise to enable acquisition of a general image of mammalian and potentially human tissue health.
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Affiliation(s)
- Boris Epel
- Department of Radiation and Cellular Oncology, Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois, USA
| | - Joseph P Y Kao
- Center for Biomedical Engineering and Technology, Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Sandra S Eaton
- Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado, USA
| | - Gareth R Eaton
- Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado, USA
| | - Howard J Halpern
- Department of Radiation and Cellular Oncology, Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois, USA
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10
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van Noorden CJ, Yetkin-Arik B, Serrano Martinez P, Bakker N, van Breest Smallenburg ME, Schlingemann RO, Klaassen I, Majc B, Habic A, Bogataj U, Galun SK, Vittori M, Erdani Kreft M, Novak M, Breznik B, Hira VV. New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases. J Histochem Cytochem 2024; 72:329-352. [PMID: 38733294 PMCID: PMC11107438 DOI: 10.1369/00221554241249515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 04/01/2024] [Indexed: 05/13/2024] Open
Abstract
Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX-XXX, XXXX).
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Affiliation(s)
- Cornelis J.F. van Noorden
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
- Ocular Angiogenesis Group, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, The Netherlands
| | - Bahar Yetkin-Arik
- Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
- Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
- Centre for Living Technologies, Alliance TU/e, WUR, UU, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Paola Serrano Martinez
- Ocular Angiogenesis Group, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, The Netherlands
| | - Noëlle Bakker
- Ocular Angiogenesis Group, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, The Netherlands
| | | | - Reinier O. Schlingemann
- Ocular Angiogenesis Group, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, The Netherlands
- Department of Ophthalmology, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, The Netherlands
- Department of Ophthalmology, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland
| | - Ingeborg Klaassen
- Ocular Angiogenesis Group, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, The Netherlands
| | - Bernarda Majc
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
| | - Anamarija Habic
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
- Jozef Stefan Postgraduate School, Ljubljana, Slovenia
| | - Urban Bogataj
- Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - S. Katrin Galun
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
| | - Milos Vittori
- Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Mateja Erdani Kreft
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Metka Novak
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
| | - Barbara Breznik
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
| | - Vashendriya V.V. Hira
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
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11
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Yao T, Wang H, Lin K, Wang R, Guo S, Chen P, Wu H, Liu T, Wang R. Exercise-induced microbial changes in preventing type 2 diabetes. SCIENCE CHINA. LIFE SCIENCES 2024; 67:892-899. [PMID: 36795181 DOI: 10.1007/s11427-022-2272-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/10/2023] [Indexed: 02/17/2023]
Abstract
The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut microbiota. Here we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and diabetes. We found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students cohort. We additionally showed that those microbial changes correlated more with handgrip strength, a simple but valuable biomarker suggestive of the diabetes states, than maximum oxygen intake, one of the key surrogates for endurance training. Moreover, the causal relationships among exercise, risks for diabetes, and gut microbiota were explored based on mediation analysis. We propose that the protective roles of exercise against type 2 diabetes are mediated, at least partly, by the gut microbiota.
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Affiliation(s)
- Ting Yao
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, 200438, China
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University School of Medicine, Xi'an, 710061, China
| | - Hui Wang
- Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism & Integrative Biology, Fudan University, Shanghai, 200433, China
| | - Kaiqing Lin
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Ruwen Wang
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Shanshan Guo
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Peijie Chen
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Hao Wu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan Microbiome Center, and Department of Bariatric and Metabolic Surgery, Huashan Hospital, Fudan University, Shanghai, 201203, China.
| | - Tiemin Liu
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, 200438, China.
- Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism & Integrative Biology, Fudan University, Shanghai, 200433, China.
- State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Human Phenome Institute, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Ru Wang
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, 200438, China.
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12
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Wang N, Yang A, Tian X, Liao J, Yang Z, Pan Y, Guo Y, He S. Label-free analysis of the β-hydroxybutyricacid drug on mitochondrial redox states repairment in type 2 diabetic mice by resonance raman scattering. Biomed Pharmacother 2024; 172:116320. [PMID: 38387134 DOI: 10.1016/j.biopha.2024.116320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 02/08/2024] [Accepted: 02/19/2024] [Indexed: 02/24/2024] Open
Abstract
BACKGROUND Mitochondrial redox imbalance underlies the pathophysiology of type2 diabetes mellitus (T2DM), and is closely related to tissue damage and dysfunction. Studies have shown the beneficial effects of dietary strategies that elevate β-hydroxybutyrate (BHB) levels in alleviating T2DM. Nevertheless, the role of BHB has not been clearly elucidated. METHODS We performed a spectral study to visualize the preventive effects of BHB on blood and multiorgan mitochondrial redox imbalance in T2DM mice via using label-free resonance Raman spectroscopy (RRS), and further explored the impact of BHB therapy on the pathology of T2DM mice by histological and biochemical analyses. FINDINGS Our data revealed that RRS-based mitochondrial redox states assay enabled clear and reliable identification of the improvement of mitochondrial redox imbalance by BHB, evidenced by the reduction of Raman peak intensity at 750 cm-1, 1128 cm-1 and 1585 cm-1 in blood, tissue as well as purified mitochondria of db/db mice and the increase of tissue mitochondrial succinic dehydrogenase (SDH) staining after BHB treatment. Exogenous supplementation of BHB was also found to attenuate T2DM pathology related to mitochondrial redox states, involving organ injury, blood glucose control, insulin resistance and systemic inflammation. INTERPRETATION Our findings provide strong evidence for BHB as a potential therapeutic strategy targeting mitochondria for T2DM.
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Affiliation(s)
- Na Wang
- Taizhou Hospital, Zhejiang University School of Medicine, Linhai, China; Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Anqi Yang
- Centre for Optical and Electromagnetic Research, National Engineering Research Center for Optical Instruments, Zhejiang Provincial Key Laboratory for Sensing Technologies, Zhejiang University, Hangzhou 310058, China
| | - Xiong Tian
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Jiaqi Liao
- Centre for Optical and Electromagnetic Research, National Engineering Research Center for Optical Instruments, Zhejiang Provincial Key Laboratory for Sensing Technologies, Zhejiang University, Hangzhou 310058, China
| | - Zhenyu Yang
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Yixiao Pan
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Yiqing Guo
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Sailing He
- Taizhou Hospital, Zhejiang University School of Medicine, Linhai, China; Centre for Optical and Electromagnetic Research, National Engineering Research Center for Optical Instruments, Zhejiang Provincial Key Laboratory for Sensing Technologies, Zhejiang University, Hangzhou 310058, China; School of Electrical Engineering, Royal Institute of Technology, Stockholm S-100 44, Sweden.
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13
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Choukroun E, Parnot M, Surmenian J, Gruber R, Cohen N, Davido N, Simonpieri A, Savoldelli C, Afota F, El Mjabber H, Choukroun J. Bone Formation and Maintenance in Oral Surgery: The Decisive Role of the Immune System-A Narrative Review of Mechanisms and Solutions. Bioengineering (Basel) 2024; 11:191. [PMID: 38391677 PMCID: PMC10886049 DOI: 10.3390/bioengineering11020191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 02/03/2024] [Accepted: 02/09/2024] [Indexed: 02/24/2024] Open
Abstract
Based on the evidence of a significant communication and connection pathway between the bone and immune systems, a new science has emerged: osteoimmunology. Indeed, the immune system has a considerable impact on bone health and diseases, as well as on bone formation during grafts and its stability over time. Chronic inflammation induces the excessive production of oxidants. An imbalance between the levels of oxidants and antioxidants is called oxidative stress. This physio-pathological state causes both molecular and cellular damage, which leads to DNA alterations, genetic mutations and cell apoptosis, and thus, impaired immunity followed by delayed or compromised wound healing. Oxidative stress levels experienced by the body affect bone regeneration and maintenance around teeth and dental implants. As the immune system and bone remodeling are interconnected, bone loss is a consequence of immune dysregulation. Therefore, oral tissue deficiencies such as periodontitis and peri-implantitis should be regarded as immune diseases. Bone management strategies should include both biological and surgical solutions. These protocols tend to improve immunity through antioxidant production to enhance bone formation and prevent bone loss. This narrative review aims to highlight the relationship between inflammation, oxidation, immunity and bone health in the oral cavity. It intends to help clinicians to detect high-risk situations in oral surgery and to propose biological and clinical solutions that will enhance patients' immune responses and surgical treatment outcomes.
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Affiliation(s)
| | | | | | - Reinhard Gruber
- Department of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
| | | | | | | | | | - Franck Afota
- Private Practice, 06000 Nice, France
- Head and Neck Institute, CHU, 06000 Nice, France
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14
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Appendino G, Gaeta S. Tigliane Diterpenoids. PROGRESS IN THE CHEMISTRY OF ORGANIC NATURAL PRODUCTS 2024; 125:1-189. [PMID: 39546131 DOI: 10.1007/978-3-031-67180-7_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Abstract
The distribution, chemistry, and molecular bioactivity of tiglianes are reviewed from the very beginning of the studies on these diterpenoids, summarizing their clinical and toxicological literature mostly in its more recent and controversial aspects, and critically analyzing various proposals for their biosynthesis.
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Affiliation(s)
- Giovanni Appendino
- Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Largo Donegani, 2, 28100, Novara, Italy.
| | - Simone Gaeta
- Research & Development-Chemistry Research, QBiotics Group Limited, 165, Moggill Road, Taringa, QLD, 4068, Australia
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15
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Bilibio BLE, Dos Reis WR, Compagnon L, de Batista DG, Sulzbacher LM, Pinheiro JF, Ludwig MS, Frizzo MN, Cruzat V, Heck TG. Effects of alternate-day fasting and time-restricted feeding in obese middle-aged female rats. Nutrition 2023; 116:112198. [PMID: 37717500 DOI: 10.1016/j.nut.2023.112198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 08/12/2023] [Accepted: 08/13/2023] [Indexed: 09/19/2023]
Abstract
OBJECTIVES Obesity is a multifactorial condition associated with metabolic alterations that can be aggravated during female aging. Calorie restriction via intermittent fasting (IF) diets may reduce body weight and therefore have the potential to decrease obesity and associated comorbidities, such as insulin resistance. This study investigated the effects of two IF protocols, alternate-day fasting (ADF) and time-restricted feeding (TRF) in middle-aged obese female rats. METHODS Wistar rats (age 15 mo) were fed with standard chow or high-fat diet for 8 wk and then separated into the following groups (n = 5-8 each) for another 8 wk: control (received standard chow), obese (received high-fat diet), obese + ADF (24-h fasting protocol), and obese + TRF (14 h daily). RESULTS At the end of the study, both IF protocols were able to reduce body weight and body mass index compared with the obese group. However, no changes were observed in adiposity and glucose homeostasis. We also found an increase in total leukocytes, lymphocytes, and monocytes in the TRF group and a higher number of platelets in the ADF group. Blood lipid profiles, including triglycerides and high-density lipoprotein, as well as liver stress responses, such as heat shock protein 70 and malondialdehyde, were not changed by IF. CONCLUSIONS Although ADF and TRF protocols resulted in a reduction of body weight and body mass index, these dietary interventions did not promote health benefits, such as reducing blood lipid profile, adiposity, and insulin resistance. In addition, ADF and TRF increased inflammatory biomarkers, which may increase the risk of obesity-associated comorbidities.
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Affiliation(s)
- Bruna L Endl Bilibio
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Integral Attention to Health, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Welerson R Dos Reis
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Letícia Compagnon
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Integral Attention to Health, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Diovana G de Batista
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Integral Attention to Health, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Mathematical and Computational Modelling, Regional University of North-western Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Lucas M Sulzbacher
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Integral Attention to Health, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Juliana F Pinheiro
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Mirna S Ludwig
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Integral Attention to Health, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Matias N Frizzo
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Integral Attention to Health, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
| | - Vinicius Cruzat
- Faculty of Health, Southern Cross University, Gold Coast, Queensland, Australia.
| | - Thiago G Heck
- Research Group in Physiology, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Integral Attention to Health, Regional University of Northwestern Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil; Postgraduate Program in Mathematical and Computational Modelling, Regional University of North-western Rio Grande do Sul State, Ijuí, Rio Grande do Sul State, Brazil
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16
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Shaukat A, Zaidi A, Anwar H, Kizilbash N. Mechanism of the antidiabetic action of Nigella sativa and Thymoquinone: a review. Front Nutr 2023; 10:1126272. [PMID: 37818339 PMCID: PMC10561288 DOI: 10.3389/fnut.2023.1126272] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 07/27/2023] [Indexed: 10/12/2023] Open
Abstract
Introduction Long used in traditional medicine, Nigella sativa (NS; Ranunculaceae) has shown significant efficacy as an adjuvant therapy for diabetes mellitus (DM) management by improving glucose tolerance, decreasing hepatic gluconeogenesis, normalizing blood sugar and lipid imbalance, and stimulating insulin secretion from pancreatic cells. In this review, the pharmacological and pharmacokinetic properties of NS as a herbal diabetes medication are examined in depth, demonstrating how it counteracts oxidative stress and the onset and progression of DM. Methods This literature review drew on databases such as Google Scholar and PubMed and various gray literature sources using search terms like the etiology of diabetes, conventional versus herbal therapy, subclinical pharmacology, pharmacokinetics, physiology, behavior, and clinical outcomes. Results The efficiency and safety of NS in diabetes, notably its thymoquinone (TQ) rich volatile oil, have drawn great attention from researchers in recent years; the specific therapeutic dose has eluded determination so far. TQ has anti-diabetic, anti-inflammatory, antioxidant, and immunomodulatory properties but has not proved druggable. DM's intimate link with oxidative stress, makes NS therapy relevant since it is a potent antioxidant that energizes the cell's endogenous arsenal of antioxidant enzymes. NS attenuates insulin resistance, enhances insulin signaling, suppresses cyclooxygenase-2, upregulates insulin-like growth factor-1, and prevents endothelial dysfunction in DM. Conclusion The interaction of NS with mainstream drugs, gut microbiota, and probiotics opens new possibilities for innovative therapies. Despite its strong potential to treat DM, NS and TQ must be examined in more inclusive clinical studies targeting underrepresented patient populations.
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Affiliation(s)
- Arslan Shaukat
- Department of Physiology, Government College University - GCU, Faisalabad, Punjab, Pakistan
| | - Arsalan Zaidi
- National Probiotic Laboratory, National Institute for Biotechnology and Genetic Engineering College - NIBGE-C, Faisalabad, Punjab, Pakistan
- Pakistan Institute of Engineering and Applied Sciences - PIEAS, Nilore, Islamabad, Pakistan
| | - Haseeb Anwar
- Department of Physiology, Government College University - GCU, Faisalabad, Punjab, Pakistan
| | - Nadeem Kizilbash
- Department Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia
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17
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Ruan S, Liu W, Wang W, Lu Y. Research Progress of SERS Sensors Based on Hydrogen Peroxide and Related Substances. Crit Rev Anal Chem 2023; 54:3570-3591. [PMID: 37695106 DOI: 10.1080/10408347.2023.2255901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Hydrogen peroxide (H2O2) has an important role in living organisms, and its detection is of great importance in medical, chemical, and food safety applications. This review provides a comparison of different types of Surface-enhanced Raman scattering (SERS) sensors for H2O2 and related substances with respect to their detection limits, which are of interest due to high sensitivity compared to conventional sensors. According to the latest research report, this review focuses on the sensing mechanism of different sensors and summarizes the linear range, detection limits, and cellular applications of new SERS sensors, and discusses the limitations in vivo and future prospects of SERS technology for the detection of H2O2.
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Affiliation(s)
- Shuyan Ruan
- College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Oriented Chemical Engineer, Fujian Key Laboratory of Polymer Materials, Engineering Research Center of Industrial Biocatalysis, Fujian Province Higher Education Institutes, Fujian Normal University, Fuzhou, Fujian, China
| | - Wenting Liu
- College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Oriented Chemical Engineer, Fujian Key Laboratory of Polymer Materials, Engineering Research Center of Industrial Biocatalysis, Fujian Province Higher Education Institutes, Fujian Normal University, Fuzhou, Fujian, China
| | - Wenxi Wang
- College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Oriented Chemical Engineer, Fujian Key Laboratory of Polymer Materials, Engineering Research Center of Industrial Biocatalysis, Fujian Province Higher Education Institutes, Fujian Normal University, Fuzhou, Fujian, China
| | - Yudong Lu
- College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Oriented Chemical Engineer, Fujian Key Laboratory of Polymer Materials, Engineering Research Center of Industrial Biocatalysis, Fujian Province Higher Education Institutes, Fujian Normal University, Fuzhou, Fujian, China
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18
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Niu Y, Chen Z, Jiang Z, Yang Y, Liu G, Cheng X, Jiang Z, Zhang G, Tong L, Tang B. Detection of Cysteine Sulfenic Acid on E. coli Proteins with a Biotin-Benzoboroxole Probe. ACS Chem Biol 2023; 18:1351-1359. [PMID: 37260364 DOI: 10.1021/acschembio.3c00073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
S-sulfenylation of cysteine residues on proteins can effectively change protein structures and accordingly regulate their functions in vivo. Investigation of S-sulfenylation in different biological environments is thus vital for a systematic understanding of cellular redox regulation. In this work, a functional probe, biotin-benzoboroxole (Bio-ben), was designed for the detection of cysteine sulfenic acid (Cys-SOH). The performance of Bio-ben was characterized by small-molecule sulfenic acid, protein models, and proteome tests via mass spectra and western blotting. The results showed that Bio-ben was validated for cysteine sulfenic acid on proteins with good capture efficiency even at low concentrations. Compared with commonly used probes such as dimedone, the current probe has significantly shortened labeling time and exhibited comparable sensitivity. The proposed method provides a new approach for exploring S-sulfenylation in the oxidative modification of proteins and is helpful for related biological and clinical applications.
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Affiliation(s)
- Yaxin Niu
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Zhenzhen Chen
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Zhongyao Jiang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Yanmei Yang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Guangzhao Liu
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Xiufen Cheng
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Zhenhao Jiang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Guanglu Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Lili Tong
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China
- Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, People's Republic of China
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19
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Yuan S, Jiang SC, Zhang ZW, Fu YF, Yang XY, Li ZL, Hu J. Rethinking of Alzheimer's disease: Lysosomal overloading and dietary therapy. Front Aging Neurosci 2023; 15:1130658. [PMID: 36861123 PMCID: PMC9968973 DOI: 10.3389/fnagi.2023.1130658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 01/30/2023] [Indexed: 02/15/2023] Open
Affiliation(s)
- Shu Yuan
- College of Resources, Sichuan Agricultural University, Chengdu, China,*Correspondence: Shu Yuan ✉
| | - Si-Cong Jiang
- Haisco Pharmaceutical Group Comp. Ltd., Chengdu, China
| | - Zhong-Wei Zhang
- College of Resources, Sichuan Agricultural University, Chengdu, China
| | - Yu-Fan Fu
- College of Resources, Sichuan Agricultural University, Chengdu, China
| | - Xin-Yue Yang
- College of Resources, Sichuan Agricultural University, Chengdu, China
| | - Zi-Lin Li
- Department of Cardiovascular Surgery, Xijing Hospital, Medical University of the Air Force, Xi'an, China
| | - Jing Hu
- School of Medicine, Northwest University, Xi'an, China
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20
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Zhang M, Li Q, Wang KL, Dong Y, Mu YT, Cao YM, Liu J, Li ZH, Cui HL, Liu HY, Hu AQ, Zheng YJ. Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese. J Transl Med 2023; 21:47. [PMID: 36698149 PMCID: PMC9875546 DOI: 10.1186/s12967-023-03902-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population. METHODS We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms. RESULTS We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05). CONCLUSIONS Genes related to lipolysis, redox reaction, and proliferation of islet β-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.
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Affiliation(s)
- Miao Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Qing Li
- Department of Obstetrics and Gynecology, Anqing Municipal Hospital, Anqing, 246003, China
| | - Kai-Lin Wang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Yao Dong
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Yu-Tong Mu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Yan-Min Cao
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Jin Liu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Zi-Heng Li
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Hui-Lu Cui
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Hai-Yan Liu
- Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing, 246003, China.
| | - An-Qun Hu
- Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing, 246003, China.
| | - Ying-Jie Zheng
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China.
- Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China.
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China.
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Hu J, Bian Q, Ma X, Xu Y, Gao J. A double-edged sword: ROS related therapies in the treatment of psoriasis. Asian J Pharm Sci 2022; 17:798-816. [PMID: 36600897 PMCID: PMC9800958 DOI: 10.1016/j.ajps.2022.10.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/27/2022] [Accepted: 10/19/2022] [Indexed: 11/15/2022] Open
Abstract
In the onset and progression of psoriasis, redox imbalance is a vital factor. It's widely accepted that too much reactive oxygen species (ROS) always make psoriasis worse. Recent research, however, has shown that the accumulation of ROS is not entirely detrimental, as it helps reduce psoriasis lesions by inhibiting epidermal proliferation and keratinocyte death. As a result, ROS appears to have two opposing effects on the treatment of psoriasis. In this review, the current ROS-related therapies for psoriasis, including basic and clinical research, are presented. Additionally, the design and therapeutic benefits of various drug delivery systems and therapeutic approaches are examined, and a potential balance between anti-oxidative stress and ROS accumulation is also trying to be investigated.
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Affiliation(s)
- Jingyi Hu
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Qiong Bian
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China,College of Pharmacy, Inner Mongolia Medical University, Hohhot 010000, China
| | - Xiaolu Ma
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yihua Xu
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jianqing Gao
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China,Jiangsu Engineering Research Center for New-type External and Transdermal Preparations, Changzhou 213149, China,Corresponding author.
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22
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Sun L, Liu T, Liu J, Gao C, Zhang X. Physical exercise and mitochondrial function: New therapeutic interventions for psychiatric and neurodegenerative disorders. Front Neurol 2022; 13:929781. [PMID: 36158946 PMCID: PMC9491238 DOI: 10.3389/fneur.2022.929781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 06/21/2022] [Indexed: 11/26/2022] Open
Abstract
Psychiatric and neurodegenerative diseases, including major depression disorder (MDD), bipolar disorder, and Alzheimer's disease, are a burden to society. Deficits of adult hippocampal neurogenesis (AHN) have been widely considered the main hallmark of psychiatric diseases as well as neurodegeneration. Herein, exploring applicable targets for improving hippocampal neural plasticity could provide a breakthrough for the development of new treatments. Emerging evidence indicates the broad functions of mitochondria in regulating cellular behaviors of neural stem cells, neural progenitors, and mature neurons in adulthood could offer multiple neural plasticities for behavioral modulation. Normalizing mitochondrial functions could be a new direction for neural plasticity enhancement. Exercise, a highly encouraged integrative method for preventing disease, has been indicated to be an effective pathway to improving both mitochondrial functions and AHN. Herein, the relative mechanisms of mitochondria in regulating neurogenesis and its effects in linking the effects of exercise to neurological diseases requires a systematic summary. In this review, we have assessed the relationship between mitochondrial functions and AHN to see whether mitochondria can be potential targets for treating neurological diseases. Moreover, as for one of well-established alternative therapeutic approaches, we summarized the evidence to show the underlying mechanisms of exercise to improve mitochondrial functions and AHN.
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Affiliation(s)
- Lina Sun
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China
- College of P.E and Sport, Beijing Normal University, Beijing, China
| | - Tianbiao Liu
- College of P.E and Sport, Beijing Normal University, Beijing, China
| | - Jingqi Liu
- College of P.E and Sport, Beijing Normal University, Beijing, China
| | - Chong Gao
- Department of Clinical Medicine, Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Institute of Brain and Cognitive Science, Zhejiang University City College, Hangzhou, China
| | - Xiaohui Zhang
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China
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23
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Chera EI, Pop TI, Pop RM, Pârvu M, Uifălean A, Cătoi FA, Cecan AD, Mîrza CM, Achimaș-Cadariu P, Pârvu AE. Flaxseed Ethanol Extract Effect in Acute Experimental Inflammation. Medicina (B Aires) 2022; 58:medicina58050582. [PMID: 35629999 PMCID: PMC9146081 DOI: 10.3390/medicina58050582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Objectives: Previous studies demonstrated antioxidant activities for flaxseed and flaxseed oil. The aim of the present study was to evaluate the prophylactic and therapeutic anti-inflammatory and antioxidant effects of flaxseed ethanol extract in acute experimental inflammation. Materials and Methods: The in vivo anti-inflammatory and antioxidant activity was evaluated on a turpentine-induced acute inflammation (6 mL/kg BW, i.m.) by measuring serum total oxidative status, total antioxidant reactivity, oxidative stress index, malondialdehyde, total thiols, total nitrites, 3-nitrotyrosine, and NFkB. The experiment was performed on nine groups (n = 5) of male rats: negative control; inflammation; three groups with seven days of flaxseed extract (100%, 50%, 25%) pretreatment followed by inflammation on day eight; three groups of inflammation followed by seven days of treatment with flaxseed extract (100%, 50%, 25%); inflammation followed by seven days of treatment with diclofenac (20 mg/kg BW). Results: Flaxseed extract anti-inflammatory activity was better in the therapeutic plan than in the prophylactic one, and consisted of NO, 3NT, and NF-κB reduction in a dose dependent way. ROS was reduced better in the therapeutic flaxseed extracts administration, and antioxidants were increased by the prophylactic flaxseed extracts administration. Both, ROS and antioxidants were influenced more by the total flaxseed extract, which was also more efficient than diclofenac. Conclusions: flaxseed extract prophylaxis has a useful antioxidant activity by increasing the antioxidants, and flaxseed extract therapy has anti-inflammatory and antioxidant activities by reducing NF-κB, RNS, and ROS.
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Affiliation(s)
- Elisabeta Ioana Chera
- Department of Pathophysiology, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (E.I.C.); (A.U.); (F.A.C.); (A.D.C.); (C.M.M.); (A.E.P.)
| | - Tiberia Ioana Pop
- Department of Technical and Soil Sciences, Faculty of Agriculture, University of Agricultural Sciences and Veterinary Medicine, 400012 Cluj-Napoca, Romania
- Correspondence: (T.I.P.); (R.M.P.); Tel.: +40-736-477327 (T.I.P.); +40-746-692265 (R.M.P.)
| | - Raluca Maria Pop
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Correspondence: (T.I.P.); (R.M.P.); Tel.: +40-736-477327 (T.I.P.); +40-746-692265 (R.M.P.)
| | - Marcel Pârvu
- Faculty of Biology and Geology, Babeș-Bolyai University, 400012 Cluj-Napoca, Romania;
| | - Ana Uifălean
- Department of Pathophysiology, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (E.I.C.); (A.U.); (F.A.C.); (A.D.C.); (C.M.M.); (A.E.P.)
| | - Florinela Adriana Cătoi
- Department of Pathophysiology, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (E.I.C.); (A.U.); (F.A.C.); (A.D.C.); (C.M.M.); (A.E.P.)
| | - Andra Diana Cecan
- Department of Pathophysiology, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (E.I.C.); (A.U.); (F.A.C.); (A.D.C.); (C.M.M.); (A.E.P.)
| | - Camelia Manuela Mîrza
- Department of Pathophysiology, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (E.I.C.); (A.U.); (F.A.C.); (A.D.C.); (C.M.M.); (A.E.P.)
| | - Patriciu Achimaș-Cadariu
- Department of Oncology, University of Medicine and Pharmacy Iuliu Hațieganu, 400012 Cluj-Napoca, Romania;
| | - Alina Elena Pârvu
- Department of Pathophysiology, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (E.I.C.); (A.U.); (F.A.C.); (A.D.C.); (C.M.M.); (A.E.P.)
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Role of Oxidative Stress in Diabetic Cardiomyopathy. Antioxidants (Basel) 2022; 11:antiox11040784. [PMID: 35453469 PMCID: PMC9030255 DOI: 10.3390/antiox11040784] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/18/2022] [Accepted: 04/12/2022] [Indexed: 02/04/2023] Open
Abstract
Type 2 diabetes is a redox disease. Oxidative stress and chronic inflammation induce a switch of metabolic homeostatic set points, leading to glucose intolerance. Several diabetes-specific mechanisms contribute to prominent oxidative distress in the heart, resulting in the development of diabetic cardiomyopathy. Mitochondrial overproduction of reactive oxygen species in diabetic subjects is not only caused by intracellular hyperglycemia in the microvasculature but is also the result of increased fatty oxidation and lipotoxicity in cardiomyocytes. Mitochondrial overproduction of superoxide anion radicals induces, via inhibition of glyceraldehyde 3-phosphate dehydrogenase, an increased polyol pathway flux, increased formation of advanced glycation end-products (AGE) and activation of the receptor for AGE (RAGE), activation of protein kinase C isoforms, and an increased hexosamine pathway flux. These pathways not only directly contribute to diabetic cardiomyopathy but are themselves a source of additional reactive oxygen species. Reactive oxygen species and oxidative distress lead to cell dysfunction and cellular injury not only via protein oxidation, lipid peroxidation, DNA damage, and oxidative changes in microRNAs but also via activation of stress-sensitive pathways and redox regulation. Investigations in animal models of diabetic cardiomyopathy have consistently demonstrated that increased expression of the primary antioxidant enzymes attenuates myocardial pathology and improves cardiac function.
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25
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Schöttker B, Larsen EL, Weimann A, Henriksen T, Brenner H, Poulsen HE. Associations of urinary metabolites of oxidized DNA and RNA with the incidence of diabetes mellitus using UPLC-MS/MS and ELISA methods. Free Radic Biol Med 2022; 183:51-59. [PMID: 35307553 DOI: 10.1016/j.freeradbiomed.2022.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/06/2022] [Accepted: 03/11/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND To evaluate the association of urinary oxidized guanine/guanosine (OxGuo) levels with incident type 2 diabetes (T2D) among older adults. METHODS A nested case-control design was applied with 440 cases of incident T2D and 440 controls, randomly sampled from all 65-75 year-old study participants of the ESTHER study, which is a population-based German cohort study with 14 years of follow-up. Analyses of 8-hydroxy-2'-deoxyguanosine (8-oxo-dGuo; DNA oxidation product) and 8-hydroxyguanosine (8-oxo-Guo; RNA oxidation product) were measured by ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS). The sum of the two OxGuo molecule concentrations was calculated and called OxGuo-UPLC-MS/MS. The corresponding OxGuo-ELISA levels were measured by Cayman's DNA/RNA oxidative damage ELISA, which detects a mix of 8-oxo-dGuo, 8-oxo-Guo and one other OxGuo molecule. Logistic regression was applied and models were adjusted for age, sex, BMI, HbA1c, and C-reactive protein levels. RESULTS 8-oxo-dGuo and 8-oxo-Guo were highly correlated with each other (r = 0.642) and weakly correlated with OxGuo-ELISA (r = 0.22 and r = 0.14, respectively). OxGuo-ELISA levels were statistically significant associated with T2D incidence (odds ratio (OR) and 95% confidence interval [95%CI] for comparison of top and bottom quartile: 1.77 [1.14; 2.76]). In contrast, the ORs did not increase stepwise from quartile 2 to 4 for neither 8-oxo-Guo, 8-oxo-dGuo levels nor OxGuo-UPLC-MS/MS and comparisons of top and bottom quartile were not statistically significant. In a post-hoc analysis comparing bottom quartile 1 with a combined group of quartile 2-4, the association of OxGuo-UPLC-MS/MS with T2D incidence reached statistical significance (OR [95%CI]: 0.66 [0.46; 0.96]) and was very similar with the one obtained for OxGuo-ELISA (OR [95%CI]: 0.66 [0.45; 0.95]). CONCLUSIONS Although only the measurements of the DNA/RNA oxidative damage ELISA kit of Cayman were statistically significantly associated with T2D incidence in the main analysis, confidence intervals overlapped and the post-hoc analysis showed that results for OxGuo-UPLC-MS/MS were quite comparable.
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Affiliation(s)
- Ben Schöttker
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany; Network Aging Research, University of Heidelberg, Bergheimer Straße 20, 69115, Heidelberg, Germany.
| | - Emil L Larsen
- Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Allan Weimann
- Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Trine Henriksen
- Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Hermann Brenner
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany; Network Aging Research, University of Heidelberg, Bergheimer Straße 20, 69115, Heidelberg, Germany
| | - Henrik E Poulsen
- Department of Endocrinology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Cardiology, Copenhagen University Hospital - North Zealand, Hillerød, Denmark
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Chen X, Yu H, Li Z, Ye W, Liu Z, Gao J, Wang Y, Li X, Zhang L, Alenina N, Bader M, Ding H, Li P, Aung LHH. Oxidative RNA Damage in the Pathogenesis and Treatment of Type 2 Diabetes. Front Physiol 2022; 13:725919. [PMID: 35418873 PMCID: PMC8995861 DOI: 10.3389/fphys.2022.725919] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 03/11/2022] [Indexed: 12/17/2022] Open
Abstract
Excessive production of free radicals can induce cellular damage, which is associated with many diseases. RNA is more susceptible to oxidative damage than DNA due to its single-stranded structure, and lack of protective proteins. Yet, oxidative damage to RNAs received little attention. Accumulating evidence reveals that oxidized RNAs may be dysfunctional and play fundamental role in the occurrence and development of type 2 diabetes (T2D) and its complications. Oxidized guanine nucleoside, 8-oxo-7, 8-dihydroguanine (8-oxoGuo) is a biomarker of RNA oxidation that could be associated with prognosis in patients with T2D. Nowadays, some clinical trials used antioxidants for the treatment of T2D, though the pharmacological effects remained unclear. In this review, we overview the cellular handling mechanisms and the consequences of the oxidative RNA damage for the better understanding of pathogenesis of T2D and may provide new insights to better therapeutic strategy.
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Affiliation(s)
- Xiatian Chen
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Hua Yu
- The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, China
| | - Zhe Li
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Wei Ye
- Jiangsu Provincial Engineering Research Center for Biomedical Materials and Advanced Medical Device, Huaiyin Institute of Technology, Huaian, China
| | - Ziqian Liu
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Jinning Gao
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
| | - Yin Wang
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
| | - Xin Li
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
| | - Lei Zhang
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
| | - Natalia Alenina
- Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany
| | - Michael Bader
- Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany
| | - Hongyan Ding
- School of Bioengineering, Suqian University, Suqian, China
| | - Peifeng Li
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
- *Correspondence: Peifeng Li, ; Lynn Htet Htet Aung,
| | - Lynn Htet Htet Aung
- Center for Molecular Genetics, Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
- *Correspondence: Peifeng Li, ; Lynn Htet Htet Aung,
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Du D, Liu C, Qin M, Zhang X, Xi T, Yuan S, Hao H, Xiong J. Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma. Acta Pharm Sin B 2022; 12:558-580. [PMID: 35256934 PMCID: PMC8897153 DOI: 10.1016/j.apsb.2021.09.019] [Citation(s) in RCA: 304] [Impact Index Per Article: 101.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.
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Key Words
- 1,3-BPG, 1,3-bisphosphoglycerate
- 2-DG, 2-deoxy-d-glucose
- 3-BrPA, 3-bromopyruvic acid
- ACC, acetyl-CoA carboxylase
- ACLY, adenosine triphosphate (ATP) citrate lyase
- ACS, acyl-CoA synthease
- AKT, protein kinase B
- AML, acute myeloblastic leukemia
- AMPK, adenosine mono-phosphate-activated protein kinase
- ASS1, argininosuccinate synthase 1
- ATGL, adipose triacylglycerol lipase
- CANA, canagliflozin
- CPT, carnitine palmitoyl-transferase
- CYP4, cytochrome P450s (CYPs) 4 family
- Cancer therapy
- DNL, de novo lipogenesis
- EMT, epithelial-to-mesenchymal transition
- ER, endoplasmic reticulum
- ERK, extracellular-signal regulated kinase
- FABP1, fatty acid binding protein 1
- FASN, fatty acid synthase
- FBP1, fructose-1,6-bisphosphatase 1
- FFA, free fatty acid
- Fatty acid β-oxidation
- G6PD, glucose-6-phosphate dehydrogenase
- GAPDH, glyceraldehyde-3-phosphate dehydrogenase
- GLS1, renal-type glutaminase
- GLS2, liver-type glutaminase
- GLUT1, glucose transporter 1
- GOT1, glutamate oxaloacetate transaminase 1
- Glutamine metabolism
- Glycolysis
- HCC, hepatocellular carcinoma
- HIF-1α, hypoxia-inducible factor-1 alpha
- HK, hexokinase
- HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase
- HSCs, hepatic stellate cells
- Hepatocellular carcinoma
- IDH2, isocitrate dehydrogenase 2
- LCAD, long-chain acyl-CoA dehydrogenase
- LDH, lactate dehydrogenase
- LPL, lipid lipase
- LXR, liver X receptor
- MAFLD, metabolic associated fatty liver disease
- MAGL, monoacyglycerol lipase
- MCAD, medium-chain acyl-CoA dehydrogenase
- MEs, malic enzymes
- MMP9, matrix metallopeptidase 9
- Metabolic dysregulation
- NADPH, nicotinamide adenine nucleotide phosphate
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- OTC, ornithine transcarbamylase
- PCK1, phosphoenolpyruvate carboxykinase 1
- PFK1, phosphofructokinase 1
- PGAM1, phosphoglycerate mutase 1
- PGK1, phosphoglycerate kinase 1
- PI3K, phosphoinositide 3-kinase
- PKM2, pyruvate kinase M2
- PPARα, peroxisome proliferator-activated receptor alpha
- PPP, pentose phosphate pathway
- Pentose phosphate pathway
- ROS, reactive oxygen species
- SCD1, stearoyl-CoA-desaturase 1
- SGLT2, sodium-glucose cotransporter 2
- SLC1A5/ASCT2, solute carrier family 1 member 5/alanine serine cysteine preferring transporter 2
- SLC7A5/LAT1, solute carrier family 7 member 5/L-type amino acid transporter 1
- SREBP1, sterol regulatory element-binding protein 1
- TAGs, triacylglycerols
- TCA cycle, tricarboxylic acid cycle
- TKIs, tyrosine kinase inhibitors
- TKT, transketolase
- Tricarboxylic acid cycle
- VEGFR, vascular endothelial growth factor receptor
- WD-fed MC4R-KO, Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO)
- WNT, wingless-type MMTV integration site family
- mIDH, mutant IDH
- mTOR, mammalian target of rapamycin
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Affiliation(s)
- Danyu Du
- Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Chan Liu
- Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Mengyao Qin
- Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Xiao Zhang
- Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Tao Xi
- Research Center of Biotechnology, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China
| | - Shengtao Yuan
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
| | - Haiping Hao
- Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
- Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
- Corresponding authors.
| | - Jing Xiong
- Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
- Corresponding authors.
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van Noorden CJ, Breznik B, Novak M, van Dijck AJ, Tanan S, Vittori M, Bogataj U, Bakker N, Khoury JD, Molenaar RJ, Hira VV. Cell Biology Meets Cell Metabolism: Energy Production Is Similar in Stem Cells and in Cancer Stem Cells in Brain and Bone Marrow. J Histochem Cytochem 2022; 70:29-51. [PMID: 34714696 PMCID: PMC8721571 DOI: 10.1369/00221554211054585] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Energy production by means of ATP synthesis in cancer cells has been investigated frequently as a potential therapeutic target in this century. Both (an)aerobic glycolysis and oxidative phosphorylation (OXPHOS) have been studied. Here, we review recent literature on energy production in glioblastoma stem cells (GSCs) and leukemic stem cells (LSCs) versus their normal counterparts, neural stem cells (NSCs) and hematopoietic stem cells (HSCs), respectively. These two cancer stem cell types were compared because their niches in glioblastoma tumors and in bone marrow are similar. In this study, it became apparent that (1) ATP is produced in NSCs and HSCs by anaerobic glycolysis, whereas fatty acid oxidation (FAO) is essential for their stem cell fate and (2) ATP is produced in GSCs and LSCs by OXPHOS despite the hypoxic conditions in their niches with FAO and amino acids providing its substrate. These metabolic processes appeared to be under tight control of cellular regulation mechanisms which are discussed in depth. However, our conclusion is that systemic therapeutic targeting of ATP production via glycolysis or OXPHOS is not an attractive option because of its unwanted side effects in cancer patients.
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Affiliation(s)
| | - Barbara Breznik
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
| | - Metka Novak
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia
| | | | | | - Miloš Vittori
- Amsterdam UMC Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Urban Bogataj
- Amsterdam UMC Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | | | - Joseph D. Khoury
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Remco J. Molenaar
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia,Department of Medical Oncology
| | - Vashendriya V.V. Hira
- Vashendriya V.V. Hira, Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna Pot 111, 1000 Ljubljana, Slovenia. E-mail:
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29
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Pattnaik S, Chaudhury B, Mohapatra M. Exploration of Inorganic Materials with Antiviral Properties. MATERIALS HORIZONS: FROM NATURE TO NANOMATERIALS 2022:53-74. [DOI: 10.1007/978-981-16-4372-9_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/19/2023]
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30
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Sharma G, Wen X, Maptue NR, Hever T, Malloy CR, Sherry AD, Khemtong C. Co-Polarized [1- 13C]Pyruvate and [1,3- 13C 2]Acetoacetate Provide a Simultaneous View of Cytosolic and Mitochondrial Redox in a Single Experiment. ACS Sens 2021; 6:3967-3977. [PMID: 34761912 DOI: 10.1021/acssensors.1c01225] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Cellular redox is intricately linked to energy production and normal cell function. Although the redox states of mitochondria and cytosol are connected by shuttle mechanisms, the redox state of mitochondria may differ from redox in the cytosol in response to stress. However, detecting these differences in functioning tissues is difficult. Here, we employed 13C magnetic resonance spectroscopy (MRS) and co-polarized [1-13C]pyruvate and [1,3-13C2]acetoacetate ([1,3-13C2]AcAc) to monitor production of hyperpolarized (HP) lactate and β-hydroxybutyrate as indicators of cytosolic and mitochondrial redox, respectively. Isolated rat hearts were examined under normoxic conditions, during low-flow ischemia, and after pretreatment with either aminooxyacetate (AOA) or rotenone. All interventions were associated with an increase in [Pi]/[ATP] measured by 31P NMR. In well-oxygenated untreated hearts, rapid conversion of HP [1-13C]pyruvate to [1-13C]lactate and [1,3-13C2]AcAc to [1,3-13C2]β-hydroxybutyrate ([1,3-13C2]β-HB) was readily detected. A significant increase in HP [1,3-13C2]β-HB but not [1-13C]lactate was observed in rotenone-treated and ischemic hearts, consistent with an increase in mitochondrial NADH but not cytosolic NADH. AOA treatments did not alter the productions of HP [1-13C]lactate or [1,3-13C2]β-HB. This study demonstrates that biomarkers of mitochondrial and cytosolic redox may be detected simultaneously in functioning tissues using co-polarized [1-13C]pyruvate and [1,3-13C2]AcAc and 13C MRS and that changes in mitochondrial redox may precede changes in cytosolic redox.
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Affiliation(s)
- Gaurav Sharma
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
| | - Xiaodong Wen
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
| | - Nesmine R. Maptue
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
| | - Thomas Hever
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
| | - Craig R. Malloy
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
| | - A. Dean Sherry
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
- Department of Chemistry, University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Chalermchai Khemtong
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610, United States
- Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida 32610, United States
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31
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Novel Antioxidant and Hypoglycemic Water-Soluble Polysaccharides from Jasmine Tea. Foods 2021; 10:foods10102375. [PMID: 34681424 PMCID: PMC8535958 DOI: 10.3390/foods10102375] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/02/2021] [Accepted: 10/05/2021] [Indexed: 11/16/2022] Open
Abstract
There have been few studies dealing with chemical elucidation and pharmacological potentials of water-soluble polysaccharides from jasmine tea, limiting their use in functional foods. In this study, water-soluble polysaccharides (named as JSP) were extracted from Jasminum sambac (L.) Aiton tea and fractionated to afford two sub-fractions (JSP-1 and JSP-2). The main structural characteristics of novel JSP sub-fractions were determined by high performance gel permeation chromatography, ultra-performance liquid chromatography-tandem mass spectrometry, Fourier transform infrared, and nuclear magnetic resonance analysis. Physiologically, the abilities of JSP-1 and JSP-2 to reduce ferric ions, scavenge DPPH and hydroxyl radicals, as well as protect islet cells were confirmed in vitro. JSP-1 exhibited better antioxidant and hypoglycemic activities than JSP-2. The molecular weights of JSP-1 and JSP-2 were 18.4 kDa and 14.1 kDa, respectively. JSP-1 was made up of glucose, galactose, rhamnose, xylose, arabinose, and galacturonic acid with molar ratios 1.14:4.69:1.00:9.92:13.79:4.09, whereas JSP-2 with a triple helical structure was composed of galactose, rhamnose, xylose, arabinose, and galacturonic acid as 3.80:1.00:8.27:11.85:5.05 of molar ratios. JSP-1 contains →1)-α-Galƒ-(3→, →1)-α-Galƒ-(2→, →1)-α-Araƒ-(5→, →1)-α-Araƒ-(3→, →1)-α-Araƒ-(3,5→, →1)-β-Xylp-(2→ and →1)-β-Xylp-(3→ residues in the backbone. These results open up new pharmacological prospects for the water-soluble polysaccharides extracted from jasmine tea.
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32
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Lennicke C, Cochemé HM. Redox metabolism: ROS as specific molecular regulators of cell signaling and function. Mol Cell 2021; 81:3691-3707. [PMID: 34547234 DOI: 10.1016/j.molcel.2021.08.018] [Citation(s) in RCA: 499] [Impact Index Per Article: 124.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/02/2021] [Accepted: 08/12/2021] [Indexed: 12/12/2022]
Abstract
Redox reactions are intrinsically linked to energy metabolism. Therefore, redox processes are indispensable for organismal physiology and life itself. The term reactive oxygen species (ROS) describes a set of distinct molecular oxygen derivatives produced during normal aerobic metabolism. Multiple ROS-generating and ROS-eliminating systems actively maintain the intracellular redox state, which serves to mediate redox signaling and regulate cellular functions. ROS, in particular hydrogen peroxide (H2O2), are able to reversibly oxidize critical, redox-sensitive cysteine residues on target proteins. These oxidative post-translational modifications (PTMs) can control the biological activity of numerous enzymes and transcription factors (TFs), as well as their cellular localization or interactions with binding partners. In this review, we describe the diverse roles of redox regulation in the context of physiological cellular metabolism and provide insights into the pathophysiology of diseases when redox homeostasis is dysregulated.
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Affiliation(s)
- Claudia Lennicke
- MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
| | - Helena M Cochemé
- MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
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Khoder-Agha F, Kietzmann T. The glyco-redox interplay: Principles and consequences on the role of reactive oxygen species during protein glycosylation. Redox Biol 2021; 42:101888. [PMID: 33602616 PMCID: PMC8113034 DOI: 10.1016/j.redox.2021.101888] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/28/2021] [Accepted: 01/29/2021] [Indexed: 12/21/2022] Open
Abstract
Reactive oxygen species (ROS) carry out prime physiological roles as intracellular signaling agents, yet pathologically high concentrations of ROS cause irreversible damage to biomolecules, alter cellular programs and contribute to various diseases. While decades of intensive research have identified redox-related patterns and signaling pathways, very few addressed how the glycosylation machinery senses and responds to oxidative stress. A common trait among ROS and glycans residing on glycoconjugates is that they are both highly dynamic, as they are quickly fine-tuned in response to stressors such as inflammation, cancer and infectious diseases. On this account, the delicate balance of the redox potential, which is tightly regulated by dozens of enzymes including NOXs, and the mitochondrial electron transport chain as well as the fluidity of glycan biosynthesis resulting from the cooperation of glycosyltransferases, glycosidases, and nucleotide sugar transporters, is paramount to cell survival. Here, we review the broad spectrum of the interplay between redox changes and glycosylation with respect to their principle consequences on human physiology.
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Affiliation(s)
- Fawzi Khoder-Agha
- Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Kietzmann
- University of Oulu, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Oulu, Finland.
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34
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Kim SW, Jung WS, Chung S, Park HY. Exercise intervention under hypoxic condition as a new therapeutic paradigm for type 2 diabetes mellitus: A narrative review. World J Diabetes 2021; 12:331-343. [PMID: 33889283 PMCID: PMC8040082 DOI: 10.4239/wjd.v12.i4.331] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/25/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
This review aims to summarize the health benefits of exposure to hypoxic conditions during exercise in patients with type 2 diabetes mellitus (T2DM). Exposure to hypoxic conditions during exercise training positively changes the physiological response in healthy subjects. Exposure to hypoxic conditions during exercise could markedly increase skeletal muscle glucose uptake compared to that in normoxic conditions. Furthermore, post-exercise insulin sensitivity of T2DM patients increases more when exercising under hypoxic than under normoxic conditions. Regular exercise under short-term hypoxic conditions can improve blood glucose control at lower workloads than in normoxic conditions. Additionally, exercise training under short-term hypoxic conditions can maximize weight loss in overweight and obese patients. Previous studies on healthy subjects have reported that regular exercise under hypoxic conditions had a more positive effect on vascular health than exercising under normoxic conditions. However, currently, evidence indicating that exposure to hypoxic conditions could positively affect T2DM patients in the long-term is lacking. Therefore, further evaluations of the beneficial effects of exercise under hypoxic conditions on the human body, considering different cycle lengths, duration of exposures, sessions per day, and the number of days, are necessary. In this review, we conclude that there is evidence that exercise under hypoxic conditions can yield health benefits, which is potentially valuable in terms of clinical care as a new intervention for T2DM patients.
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Affiliation(s)
- Sung-Woo Kim
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
| | - Won-Sang Jung
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
| | - Sochung Chung
- Department of Pediatrics, Konkuk University Medical Center, Research Institute of Medical Science, Konkuk University, School of Medicine, Seoul 05029, South Korea
| | - Hun-Young Park
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
- Department of Sports Science and Medicine, Konkuk University, Seoul 05029, South Korea
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35
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van Noorden CJ, Hira VV, van Dijck AJ, Novak M, Breznik B, Molenaar RJ. Energy Metabolism in IDH1 Wild-Type and IDH1-Mutated Glioblastoma Stem Cells: A Novel Target for Therapy? Cells 2021; 10:cells10030705. [PMID: 33810170 PMCID: PMC8005124 DOI: 10.3390/cells10030705] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 03/12/2021] [Accepted: 03/14/2021] [Indexed: 12/14/2022] Open
Abstract
Cancer is a redox disease. Low levels of reactive oxygen species (ROS) are beneficial for cells and have anti-cancer effects. ROS are produced in the mitochondria during ATP production by oxidative phosphorylation (OXPHOS). In the present review, we describe ATP production in primary brain tumors, glioblastoma, in relation to ROS production. Differentiated glioblastoma cells mainly use glycolysis for ATP production (aerobic glycolysis) without ROS production, whereas glioblastoma stem cells (GSCs) in hypoxic periarteriolar niches use OXPHOS for ATP and ROS production, which is modest because of the hypoxia and quiescence of GSCs. In a significant proportion of glioblastoma, isocitrate dehydrogenase 1 (IDH1) is mutated, causing metabolic rewiring, and all cancer cells use OXPHOS for ATP and ROS production. Systemic therapeutic inhibition of glycolysis is not an option as clinical trials have shown ineffectiveness or unwanted side effects. We argue that systemic therapeutic inhibition of OXPHOS is not an option either because the anti-cancer effects of ROS production in healthy cells is inhibited as well. Therefore, we advocate to remove GSCs out of their hypoxic niches by the inhibition of their binding to niches to enable their differentiation and thus increase their sensitivity to radiotherapy and/or chemotherapy.
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Affiliation(s)
- Cornelis J.F. van Noorden
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna Pot 111, 1000 Ljubljana, Slovenia; (V.V.V.H.); (M.N.); (B.B.); (R.J.M.)
- Department of Medical Biology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
- Correspondence: ; Tel.: +31-638-639-561
| | - Vashendriya V.V. Hira
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna Pot 111, 1000 Ljubljana, Slovenia; (V.V.V.H.); (M.N.); (B.B.); (R.J.M.)
| | - Amber J. van Dijck
- Department of Medical Biology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
| | - Metka Novak
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna Pot 111, 1000 Ljubljana, Slovenia; (V.V.V.H.); (M.N.); (B.B.); (R.J.M.)
| | - Barbara Breznik
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna Pot 111, 1000 Ljubljana, Slovenia; (V.V.V.H.); (M.N.); (B.B.); (R.J.M.)
| | - Remco J. Molenaar
- Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna Pot 111, 1000 Ljubljana, Slovenia; (V.V.V.H.); (M.N.); (B.B.); (R.J.M.)
- Department of Medical Oncology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
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36
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De la Rosa A, Gomez-Cabrera MC, Vinue A, Gonzalez-Navarro H, Sanchez-Andres JV, Viña J. Overexpression of glucose 6 phosphate dehydrogenase preserves mouse pancreatic beta cells function until late in life. Free Radic Biol Med 2021; 164:149-153. [PMID: 33418115 DOI: 10.1016/j.freeradbiomed.2020.12.439] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/01/2020] [Accepted: 12/25/2020] [Indexed: 10/22/2022]
Abstract
NAD(P)H donates electrons for reductive biosynthesis and antioxidant defense across all forms of life. Glucose-6-phosphate dehydrogenase (G6PD) is a critical enzyme to provide NADPH. G6PD deficiency is present in more than 400 million people worldwide. This enzymopathy provides protection against malaria but sensitizes cells to oxidative stressors. Oxidative stress has been involved in the pathogenesis of the diabetic complications and several studies have provided evidences of a link between G6PD deficiency and type 2 diabetes (T2D). We hypothesized that a moderate overexpression of G6PD (G6PD-Tg) could protect β-cells from age-associated oxidative stress thus reducing the risk of developing T2D. Here we report, that G6PD-Tg mice show an improved glucose tolerance and insulin sensitivity when compared to old age-matched Wild Type (WT) ones. This is accompanied by a decrease in oxidative damage and stress markers in the pancreas of the old Tg animals (20-24month-old). Pancreatic β-cells progress physiologically towards a state of reduced responsiveness to glucose. In pancreatic islets isolated from G6PD-Tg and WT animals at different ages, and using electrophysiological techniques, we demonstrate a wider range of response to glucose in the G6PD-Tg cells that may explain the improvements in glucose tolerance and insulin sensitivity. Together, our results show that overexpression of G6PD maintains pancreatic β-cells from old mice in a "juvenile-like" state and points to the G6PD dependent generation of NADPH as an important factor to improve the natural history of diabetes.
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Affiliation(s)
- Adrian De la Rosa
- Freshage Research Group. Department of Physiology. Faculty of Medicine, University of Valencia and CIBERFES. Institute of Health Research-INCLIVA, Valencia, Spain
| | - Mari Carmen Gomez-Cabrera
- Freshage Research Group. Department of Physiology. Faculty of Medicine, University of Valencia and CIBERFES. Institute of Health Research-INCLIVA, Valencia, Spain
| | - Angela Vinue
- Institute of Health Research-INCLIVA, Valencia, Spain
| | - Herminia Gonzalez-Navarro
- Institute of Health Research-INCLIVA, Valencia, Spain and CIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research-ISCIII, Madrid, Spain
| | | | - Jose Viña
- Freshage Research Group. Department of Physiology. Faculty of Medicine, University of Valencia and CIBERFES. Institute of Health Research-INCLIVA, Valencia, Spain
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37
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Mosleth EF, Vedeler CA, Liland KH, McLeod A, Bringeland GH, Kroondijk L, Berven FS, Lysenko A, Rawlings CJ, Eid KEH, Opsahl JA, Gjertsen BT, Myhr KM, Gavasso S. Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis. Sci Rep 2021; 11:4087. [PMID: 33602999 PMCID: PMC7892850 DOI: 10.1038/s41598-021-82388-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 01/18/2021] [Indexed: 12/11/2022] Open
Abstract
Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease.
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Affiliation(s)
- Ellen F Mosleth
- Nofima AS, Norwegian Institute of Food, Fisheries and Aquaculture Research, Osloveien 1, 1430, Ås, Norway.
- Rothamsted Research, Harpenden, Hertfordshire, AL5 2JQ, UK.
| | - Christian Alexander Vedeler
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - Kristian Hovde Liland
- Nofima AS, Norwegian Institute of Food, Fisheries and Aquaculture Research, Osloveien 1, 1430, Ås, Norway
- Faculty of Science and Technology, Norwegian University of Life Sciences, 1430, Ås, Norway
| | - Anette McLeod
- Nofima AS, Norwegian Institute of Food, Fisheries and Aquaculture Research, Osloveien 1, 1430, Ås, Norway
- Center for Laboratory Medicine, Østfold Hospital Trust, Grålum, Norway
| | - Gerd Haga Bringeland
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - Liesbeth Kroondijk
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | | | - Artem Lysenko
- Rothamsted Research, Harpenden, Hertfordshire, AL5 2JQ, UK
- Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | | | - Karim El-Hajj Eid
- Nofima AS, Norwegian Institute of Food, Fisheries and Aquaculture Research, Osloveien 1, 1430, Ås, Norway
- Faculty of Science and Technology, Norwegian University of Life Sciences, 1430, Ås, Norway
| | - Jill Anette Opsahl
- Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway
| | - Bjørn Tore Gjertsen
- Center for Cancer Biomarkers (CCBIO), Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway
- Department of Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway
| | - Kjell-Morten Myhr
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - Sonia Gavasso
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
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Remigante A, Morabito R, Marino A. Band 3 protein function and oxidative stress in erythrocytes. J Cell Physiol 2021; 236:6225-6234. [PMID: 33559172 DOI: 10.1002/jcp.30322] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 01/24/2021] [Accepted: 01/28/2021] [Indexed: 12/17/2022]
Abstract
Band 3 protein (B3p), anion transporter, allows the HCO3 - /Cl- exchange across plasma membrane and plays an important role for erythrocytes homeostasis. In addition, B3p is linked to proteins cytoskeleton, thus contributing to cell shape and deformability, essential to erythrocytes adjustment within narrowest capillaries. Taking into account that erythrocytes are a suitable cell model to investigate the response of the oxidative stress effects, B3p functions, and specifically anion exchange capability, determining the rate constant for SO4 2- uptake, has been considered. As, in the latter years, rising attention has been addressed to membrane transport system, and particularly to this protein, the present mini-review has been conceived to report the most recent knowledge about B3p, with specific regard to its functions in oxidative stress conditions, including oxidative stress-related diseases.
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Affiliation(s)
- Alessia Remigante
- Institute of Biophysics, National Research Council, Genoa, Italy.,Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Rossana Morabito
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Angela Marino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
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Ke B, Zhang T, An T, Lu R. Soy isoflavones ameliorate the cognitive dysfunction of Goto-Kakizaki rats by activating the Nrf2-HO-1 signalling pathway. Aging (Albany NY) 2020; 12:21344-21354. [PMID: 33180745 PMCID: PMC7695387 DOI: 10.18632/aging.103877] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023]
Abstract
Soy isoflavones (SIF) are soybean phytochemicals that are considered to be biologically active components that protect from neurodegenerative diseases. In this study, the therapeutic effect of SIF was evaluated in a diabetic Goto-Kakizaki (GK) rat model. Twenty male GK rats were randomly divided into diabetes mellitus (DM) model group and SIF+DM group (n=10 in each group). Twenty age-matched male Wistar rats were randomly divided into control group (CON group) and CON+SIF group, with 10 rats in each group. The learning and memory functions of the animals were determined by the Morris water maze (MWM) test. Hematoxylin-eosin staining (HE) was performed to examine pyramidal neuron loss in the CA1 area of the hippocampus. Markers of oxidative stress (OS) were measured to evaluate oxidative stress-mediated injury. RT-PCR and western blotting were used to analyze the expression of nuclear factorerythroid2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone1 (NQO1). Treatment with SIF for 4 weeks alleviated the cognitive dysfunction of the GK rats as determined by the MWM test. Moreover, SIF treatment also reduced diabetes-related oxidative reactions. In addition, SIF enhanced the expression of Nrf2, HO-1 and NQO1, suggesting a potential antioxidation mechanism for the effect of SIF. These findings suggest that SIF can be considered candidates for inhibiting the progression of diabetes-induced cognitive dysfunction, provide novel insights into the antioxidant effect of SIF and further strengthen the link between oxidative stress and diabetes.
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Affiliation(s)
- Boxi Ke
- Department of Neurology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang Province, PR China
| | - Tianmeng Zhang
- Jitang College of North China University of Science and Technology, Tangshan, Hebei Province, PR China
| | - Tianyang An
- Jitang College of North China University of Science and Technology, Tangshan, Hebei Province, PR China
| | - Rong Lu
- Anesthesiology Department, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang Province, PR China
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Zhang Q, Shen F, Shen W, Xia J, Wang J, Zhao Y, Zhang Z, Sun Y, Qian M, Ding S. High-Intensity Interval Training Attenuates Ketogenic Diet-Induced Liver Fibrosis in Type 2 Diabetic Mice by Ameliorating TGF-β1/Smad Signaling. Diabetes Metab Syndr Obes 2020; 13:4209-4219. [PMID: 33192083 PMCID: PMC7656782 DOI: 10.2147/dmso.s275660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 10/14/2020] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE Ketogenic diet (KD) and high-intensity interval training (HIIT) have preclinical benefits for type 2 diabetes (Db). However, the health risks of long-term KD use in diabetes should be ascertained and prevented. We hypothesized that KD-induced liver fibrosis in type 2 diabetic mice could be ameliorated by HIIT. METHODS Streptozotocin-induced type 2 diabetic mice were divided into high-fat diet (HFD) control (Db+HFD+Sed), KD control (Db+KD+Sed), HFD coupled with HIIT (Db+HFD+HIIT), and KD coupled with HIIT (Db+KD+HIIT) groups (n=6, per group). Control mice were kept in sedentary (Sed), while HIIT group mice underwent 40-minute high-intensity interval training three alternate days per week. After 8-week intervention, the indicators of body weight and insulin resistance, oxidative stress markers, hepatic fibrosis, genetic and protein expression of related pathways were tested. RESULTS We found that fasting blood glucose level was reduced in the Db+HFD+HIIT, Db+KD+Sed, and Db+KD+HIIT groups. Insulin sensitivity was increased in diabetic mice of these groups, whereas ROS levels were decreased in mice that underwent HIIT. The immunohistochemical staining of liver, serum index, and hepatic parameters of diabetic mice in the KD group revealed liver fibrosis, which was significantly attenuated by HIIT. Besides, these effects of HIIT were the outcome of hepatic stellate cell's inactivation, reduced protein expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases, and the inhibition of TGF-β1/Smad signaling. CONCLUSION KD had a profound fibrotic effect on the liver of type 2 diabetic mice, whereas HIIT ameliorated this effect. KD did not show any apparent benefit as far as glucose tolerance and homeostasis were concerned. Concisely, our results demonstrated that KD should be coupled with HIIT for the prevention and preclinical mitigation of type 2 diabetes.
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Affiliation(s)
- Qiang Zhang
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
| | - Fei Shen
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
| | - WenQing Shen
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
| | - Jie Xia
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
| | - Jing Wang
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
| | - Yu Zhao
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- Center for Physical Education, Xi’an Jiaotong University, Xi’an, Shaanxi710049, People’s Republic of China
| | - Zhe Zhang
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
| | - Yi Sun
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
| | - Min Qian
- Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai200241, People’s Republic of China
| | - ShuZhe Ding
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai200241, People’s Republic of China
- School of Physical Education & Health, East China Normal University, Shanghai200241, People’s Republic of China
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Hidalgo-Mora JJ, Cortés-Sierra L, García-Pérez MÁ, Tarín JJ, Cano A. Diet to Reduce the Metabolic Syndrome Associated with Menopause. The Logic for Olive Oil. Nutrients 2020; 12:nu12103184. [PMID: 33081027 PMCID: PMC7603201 DOI: 10.3390/nu12103184] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 10/13/2020] [Accepted: 10/14/2020] [Indexed: 12/12/2022] Open
Abstract
The rates of metabolic syndrome are increasing in parallel with the increasing prevalence of obesity, primarily due to its concomitant insulin resistance. This is particularly concerning for women, as the years around menopause are accompanied by an increase in visceral obesity, a strong determinant of insulin resistance. A fall in estrogens and increase in the androgen/estrogen ratio is attributed a determining role in this process, which has been confirmed in other physiological models, such as polycystic ovary syndrome. A healthy lifestyle, with special emphasis on nutrition, has been recommended as a first-line strategy in consensuses and guidelines. A consistent body of evidence has accumulated suggesting that the Mediterranean diet, with olive oil as a vital component, has both health benefits and acceptable adherence. Herein, we provide an updated overview of current knowledge on the benefits of olive oil most relevant to menopause-associated metabolic syndrome, including an analysis of the components with the greatest health impact, their effect on basic mechanisms of disease, and the state of the art regarding their action on the main features of metabolic syndrome.
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Affiliation(s)
- Juan José Hidalgo-Mora
- Service of Obstetrics and Gynecology, Hospital Clínico Universitario—INCLIVA, Av Blasco Ibáñez 17, 46010 Valencia, Spain; (J.J.H.-M.); (L.C.-S.)
| | - Laura Cortés-Sierra
- Service of Obstetrics and Gynecology, Hospital Clínico Universitario—INCLIVA, Av Blasco Ibáñez 17, 46010 Valencia, Spain; (J.J.H.-M.); (L.C.-S.)
| | - Miguel-Ángel García-Pérez
- Department of Genetics, Faculty of Biological Sciences, University of Valencia, Burjassot, and INCLIVA, Av Blasco Ibáñez 17, 46010 Valencia, Spain;
| | - Juan J. Tarín
- Department of Cellular Biology, Functional Biology and Physical Anthropology, Faculty of Biological Sciences, University of Valencia, Burjassot, 46100 Valencia, Spain;
| | - Antonio Cano
- Service of Obstetrics and Gynecology, Hospital Clínico Universitario—INCLIVA, Av Blasco Ibáñez 17, 46010 Valencia, Spain; (J.J.H.-M.); (L.C.-S.)
- Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Av Blasco Ibáñez 15, 46010 Valencia, Spain
- Correspondence: ; Tel.: +34-96-983087
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Carter CS, Huang SC, Searby CC, Cassaidy B, Miller MJ, Grzesik WJ, Piorczynski TB, Pak TK, Walsh SA, Acevedo M, Zhang Q, Mapuskar KA, Milne GL, Hinton AO, Guo DF, Weiss R, Bradberry K, Taylor EB, Rauckhorst AJ, Dick DW, Akurathi V, Falls-Hubert KC, Wagner BA, Carter WA, Wang K, Norris AW, Rahmouni K, Buettner GR, Hansen JM, Spitz DR, Abel ED, Sheffield VC. Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes. Cell Metab 2020; 32:561-574.e7. [PMID: 33027675 PMCID: PMC7819711 DOI: 10.1016/j.cmet.2020.09.012] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 06/29/2020] [Accepted: 09/11/2020] [Indexed: 12/17/2022]
Abstract
Aberrant redox signaling underlies the pathophysiology of many chronic metabolic diseases, including type 2 diabetes (T2D). Methodologies aimed at rebalancing systemic redox homeostasis have had limited success. A noninvasive, sustained approach would enable the long-term control of redox signaling for the treatment of T2D. We report that static magnetic and electric fields (sBE) noninvasively modulate the systemic GSH-to-GSSG redox couple to promote a healthier systemic redox environment that is reducing. Strikingly, when applied to mouse models of T2D, sBE rapidly ameliorates insulin resistance and glucose intolerance in as few as 3 days with no observed adverse effects. Scavenging paramagnetic byproducts of oxygen metabolism with SOD2 in hepatic mitochondria fully abolishes these insulin sensitizing effects, demonstrating that mitochondrial superoxide mediates induction of these therapeutic changes. Our findings introduce a remarkable redox-modulating phenomenon that exploits endogenous electromagneto-receptive mechanisms for the noninvasive treatment of T2D, and potentially other redox-related diseases.
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Affiliation(s)
- Calvin S Carter
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA.
| | - Sunny C Huang
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA; Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Charles C Searby
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Benjamin Cassaidy
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Michael J Miller
- Department of Physics and Astronomy, University of Iowa, Iowa City, IA, USA
| | - Wojciech J Grzesik
- Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Ted B Piorczynski
- Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, USA
| | - Thomas K Pak
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA; Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Susan A Walsh
- Department of Radiology, Division of Nuclear Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Michael Acevedo
- Department of Radiology, Division of Nuclear Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Qihong Zhang
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Kranti A Mapuskar
- Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Ginger L Milne
- Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Antentor O Hinton
- Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Deng-Fu Guo
- Department of Neuroscience and Pharmacology, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Robert Weiss
- Department of Internal Medicine, Division of Cardiology, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Kyle Bradberry
- Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Eric B Taylor
- Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Molecular Physiology and Biophysics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Adam J Rauckhorst
- Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Molecular Physiology and Biophysics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - David W Dick
- Department of Radiology, Division of Nuclear Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Vamsidhar Akurathi
- Department of Radiology, Division of Nuclear Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Kelly C Falls-Hubert
- Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Brett A Wagner
- Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Walter A Carter
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Kai Wang
- College of Public Health, Department of Biostatistics, University of Iowa, Iowa City, IA, USA
| | - Andrew W Norris
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Kamal Rahmouni
- Department of Neuroscience and Pharmacology, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Garry R Buettner
- Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Jason M Hansen
- Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, USA
| | - Douglas R Spitz
- Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - E Dale Abel
- Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Iowa Hospitals & Clinics, Iowa City, IA, USA
| | - Val C Sheffield
- Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA.
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Scheffer DDL, Latini A. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165823. [PMID: 32360589 PMCID: PMC7188661 DOI: 10.1016/j.bbadis.2020.165823] [Citation(s) in RCA: 205] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 04/07/2020] [Accepted: 04/25/2020] [Indexed: 12/13/2022]
Abstract
A wide array of molecular pathways has been investigated during the past decade in order to understand the mechanisms by which the practice of physical exercise promotes neuroprotection and reduces the risk of developing communicable and non-communicable chronic diseases. While a single session of physical exercise may represent a challenge for cell homeostasis, repeated physical exercise sessions will improve immunosurveillance and immunocompetence. Additionally, immune cells from the central nervous system will acquire an anti-inflammatory phenotype, protecting central functions from age-induced cognitive decline. This review highlights the exercise-induced anti-inflammatory effect on the prevention or treatment of common chronic clinical and experimental settings. It also suggests the use of pterins in biological fluids as sensitive biomarkers to follow the anti-inflammatory effect of physical exercise.
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Affiliation(s)
- Débora da Luz Scheffer
- Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
| | - Alexandra Latini
- Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
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Bellezza I, Riuzzi F, Chiappalupi S, Arcuri C, Giambanco I, Sorci G, Donato R. Reductive stress in striated muscle cells. Cell Mol Life Sci 2020; 77:3547-3565. [PMID: 32072237 PMCID: PMC11105111 DOI: 10.1007/s00018-020-03476-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 01/17/2020] [Accepted: 02/03/2020] [Indexed: 12/11/2022]
Abstract
Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathione disulfide and NADH/NAD+ ratios. Reductive stress is emerging as an important pathophysiological event in several diseased states, being as detrimental as is oxidative stress. Occurrence of reductive stress has been documented in several cardiomyopathies and is an important pathophysiological factor particularly in coronary artery disease and myocardial infarction. Excess activation of the transcription factor, Nrf2-the master regulator of the antioxidant response-, consequent in most cases to defective autophagy, can lead to reductive stress. In addition, hyperglycemia-induced activation of the polyol pathway can lead to increased NADH/NAD+ ratio, which might translate into increased levels of hydrogen sulfide-via enhanced activity of cystathionine β-synthase-that would fuel reductive stress through inhibition of mitochondrial complex I. Reductive stress may be either a potential weapon against cancer priming tumor cells to apoptosis or a cancer's ally promoting tumor cell proliferation and making tumor cells resistant to reactive oxygen species-inducing drugs. In non-cancer pathological states reductive stress is definitely harmful paradoxically leading to reactive oxygen species overproduction via excess NADPH oxidase 4 activity. In face of the documented occurrence of reductive stress in several heart diseases, there is much less information about the occurrence and effects of reductive stress in skeletal muscle tissue. In the present review we describe relevant results emerged from studies of reductive stress in the heart and review skeletal muscle conditions in which reductive stress has been experimentally documented and those in which reductive stress might have an as yet unrecognized pathophysiological role. Establishing whether reductive stress has a (patho)physiological role in skeletal muscle will hopefully contribute to answer the question whether antioxidant supplementation to the general population, athletes, and a large cohort of patients (e.g. heart, sarcopenic, dystrophic, myopathic, cancer, and bronco-pulmonary patients) is harmless or detrimental.
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Affiliation(s)
- Ilaria Bellezza
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
| | - Francesca Riuzzi
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy
| | - Sara Chiappalupi
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy
| | - Cataldo Arcuri
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
| | - Ileana Giambanco
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
| | - Guglielmo Sorci
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy
- Centro Universitario Di Ricerca Sulla Genomica Funzionale, University of Perugia, 06132, Perugia, Italy
| | - Rosario Donato
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy.
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy.
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Khan H, Ullah H, Khattak S, Aschner M, Aguilar CN, Halimi SMA, Cauli O, Shah SMM. Therapeutic potential of alkaloids in autoimmune diseases: Promising candidates for clinical trials. Phytother Res 2020; 35:50-62. [PMID: 32667693 DOI: 10.1002/ptr.6763] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/23/2020] [Accepted: 05/16/2020] [Indexed: 02/05/2023]
Abstract
Clinical investigations have characterized numerous disorders like autoimmune diseases, affecting the population at a rate of approximately 8-10%. These disorders are characterized by T-cell and auto-antibodies responses to self-molecules by immune system reactivity. Several therapeutic options have been adopted in clinics to combat such diseases, however, most of them are recurring. Thus, the discovery of new effective agents for the treatment of autoimmune diseases is paramount. In this context, natural products might be a useful alternative to the current therapies. Plant alkaloids with their substantial therapeutic history can be particularly interesting candidates for the alleviation of autoimmune ailments. This review encompasses various alkaloids with significant effects against autoimmune diseases in preclinical trials. These results suggest further clinical assessment with respect to autoimmune illnesses. Furthermore, the application of modern technologies such as nanoformulation could be also helpful in the design of more effective therapies and thus further studies are needed to decipher their therapeutic efficacy as well as potential limitations.
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Affiliation(s)
- Haroon Khan
- Abdul Wali khan university Mardan, Abdul Wali khan university Mardan, Department of Pharmacy, Abdul Wali Khan university Mardan, Pakistan, Mardan, Pakistan, 23200, Pakistan
| | - Hammad Ullah
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Sumaira Khattak
- Abdul Wali khan university Mardan, Abdul Wali khan university Mardan, Department of Pharmacy, Abdul Wali Khan university Mardan, Pakistan, Mardan, Pakistan, 23200, Pakistan
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, New York, USA
| | - Cristobal N Aguilar
- School of Chemistry, Universidad Autónoma de Coahuila Saltillo, Saltillo, Mexico
| | - Syed M A Halimi
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
| | - Omar Cauli
- Department of Nursing, University of Valencia, Valencia, Spain
| | - Syed M M Shah
- Department of Pharmacy, University of Swabi Pakistan, Swabi, Pakistan
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Lu QB. Reaction Cycles of Halogen Species in the Immune Defense: Implications for Human Health and Diseases and the Pathology and Treatment of COVID-19. Cells 2020; 9:cells9061461. [PMID: 32545714 PMCID: PMC7349336 DOI: 10.3390/cells9061461] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/01/2020] [Accepted: 06/10/2020] [Indexed: 12/12/2022] Open
Abstract
There is no vaccine or specific antiviral treatment for COVID-19, which is causing a global pandemic. One current focus is drug repurposing research, but those drugs have limited therapeutic efficacies and known adverse effects. The pathology of COVID-19 is essentially unknown. Without this understanding, it is challenging to discover a successful treatment to be approved for clinical use. This paper addresses several key biological processes of reactive oxygen, halogen and nitrogen species (ROS, RHS and RNS) that play crucial physiological roles in organisms from plants to humans. These include why superoxide dismutases, the enzymes to catalyze the formation of H2O2, are required for protecting ROS-induced injury in cell metabolism, why the amount of ROS/RNS produced by ionizing radiation at clinically relevant doses is ~1000 fold lower than the endogenous ROS/RNS level routinely produced in the cell and why a low level of endogenous RHS plays a crucial role in phagocytosis for immune defense. Herein we propose a plausible amplification mechanism in immune defense: ozone-depleting-like halogen cyclic reactions enhancing RHS effects are responsible for all the mentioned physiological functions, which are activated by H2O2 and deactivated by NO signaling molecule. Our results show that the reaction cycles can be repeated thousands of times and amplify the RHS pathogen-killing (defense) effects by 100,000 fold in phagocytosis, resembling the cyclic ozone-depleting reactions in the stratosphere. It is unraveled that H2O2 is a required protective signaling molecule (angel) in the defense system for human health and its dysfunction can cause many diseases or conditions such as autoimmune disorders, aging and cancer. We also identify a class of potent drugs for effective treatment of invading pathogens such as HIV and SARS-CoV-2 (COVID-19), cancer and other diseases, and provide a molecular mechanism of action of the drugs or candidates.
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Affiliation(s)
- Qing-Bin Lu
- Department of Physics and Astronomy and Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada
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Influence of Long-Term Fasting on Blood Redox Status in Humans. Antioxidants (Basel) 2020; 9:antiox9060496. [PMID: 32517172 PMCID: PMC7346198 DOI: 10.3390/antiox9060496] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/14/2020] [Accepted: 06/04/2020] [Indexed: 12/11/2022] Open
Abstract
Fasting is increasingly practiced to improve health and general well-being, as well as for its cytoprotective effects. Changes in blood redox status, linked to the development of a variety of metabolic diseases, have been recently documented during calorie restriction and intermittent fasting, but not with long-term fasting (LF). We investigated some parameters of the blood redox profile in 109 subjects before and after a 10-day fasting period. Fasting resulted in a significant reduction in body weight, improved well-being and had a beneficial modulating effect on blood lipids and glucose regulation. We observed that fasting decreased lipid peroxidation (TBARS) and increased total antioxidant capacity (TAC) in plasma, concomitant with a uric acid elevation, known to be associated with fasting and did not cause gout attacks. Reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase in erythrocytes did not show significant changes. In addition, reduction in body weight, waist circumference, and glucose levels were associated to a reduced lipid peroxidation. Similar results were obtained by grouping subjects on the basis of the changes in their GSH levels, showing that a period of 10 days fasting improves blood redox status regardless of GSH status in the blood.
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Louzada RA, Bouviere J, Matta LP, Werneck-de-Castro JP, Dupuy C, Carvalho DP, Fortunato RS. Redox Signaling in Widespread Health Benefits of Exercise. Antioxid Redox Signal 2020; 33:745-760. [PMID: 32174127 DOI: 10.1089/ars.2019.7949] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Significance: Exercise-induced reactive oxygen species (ROS) production activates multiple intracellular signaling pathways through genomic and nongenomic mechanisms that are responsible for the beneficial effects of exercise in muscle. Beyond the positive effect of exercise on skeletal muscle cells, other tissues such as white and brown adipose, liver, central nervous system, endothelial, heart, and endocrine organ tissues are also responsive to exercise. Recent Advances: Crosstalk between different cells is essential to achieve homeostasis and to promote the benefits of exercise through paracrine or endocrine signaling. This crosstalk can be mediated by different effectors that include the secretion of metabolites of muscle contraction, myokines, and exosomes. During the past 20 years, it has been demonstrated that contracting muscle cells produce and secrete different classes of myokines, which functionally link muscle with nearly all other cell types. Critical Issues: The redox signaling behind this exercise-induced crosstalk is now being decoded. Many of these widespread beneficial effects of exercise require not only a complex ROS-dependent intramuscular signaling cascade but simultaneously, an integrated network with many remote tissues. Future Directions: Strong evidence suggests that the powerful beneficial effect of regular physical activity for preventing (or treating) a large range of disorders might also rely on ROS-mediated signaling. Within a contracting muscle, ROS signaling may control exosomes and myokines secretion. In remote tissues, exercise generates regular and synchronized ROS waves, creating a transient pro-oxidative environment in many cells. These new concepts integrate exercise, ROS-mediated signaling, and the widespread health benefits of exercise.
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Affiliation(s)
- Ruy A Louzada
- Institut of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Université Paris-Sud, Orsay, UMR 8200 CNRS and Institut Gustave Roussy, Villejuif, France
| | - Jessica Bouviere
- Institut of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leonardo P Matta
- Institut of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Joao Pedro Werneck-de-Castro
- Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Corinne Dupuy
- Université Paris-Sud, Orsay, UMR 8200 CNRS and Institut Gustave Roussy, Villejuif, France
| | - Denise P Carvalho
- Institut of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Rodrigo S Fortunato
- Institut of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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49
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Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 2020; 21:363-383. [PMID: 32231263 DOI: 10.1038/s41580-020-0230-3] [Citation(s) in RCA: 2648] [Impact Index Per Article: 529.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2020] [Indexed: 02/07/2023]
Abstract
'Reactive oxygen species' (ROS) is an umbrella term for an array of derivatives of molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation of the different ROS leads to molecular damage, denoted as 'oxidative distress'. Here we focus on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as 'oxidative eustress'. Two species, hydrogen peroxide (H2O2) and the superoxide anion radical (O2·-), are key redox signalling agents generated under the control of growth factors and cytokines by more than 40 enzymes, prominently including NADPH oxidases and the mitochondrial electron transport chain. At the low physiological levels in the nanomolar range, H2O2 is the major agent signalling through specific protein targets, which engage in metabolic regulation and stress responses to support cellular adaptation to a changing environment and stress. In addition, several other reactive species are involved in redox signalling, for instance nitric oxide, hydrogen sulfide and oxidized lipids. Recent methodological advances permit the assessment of molecular interactions of specific ROS molecules with specific targets in redox signalling pathways. Accordingly, major advances have occurred in understanding the role of these oxidants in physiology and disease, including the nervous, cardiovascular and immune systems, skeletal muscle and metabolic regulation as well as ageing and cancer. In the past, unspecific elimination of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting disease initiation and progression in clinical trials. However, controlling specific ROS-mediated signalling pathways by selective targeting offers a perspective for a future of more refined redox medicine. This includes enzymatic defence systems such as those controlled by the stress-response transcription factors NRF2 and nuclear factor-κB, the role of trace elements such as selenium, the use of redox drugs and the modulation of environmental factors collectively known as the exposome (for example, nutrition, lifestyle and irradiation).
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Affiliation(s)
- Helmut Sies
- Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. .,Leibniz Research Institute for Environmental Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | - Dean P Jones
- Department of Medicine, Emory University, Atlanta, GA, USA.
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Hsu YH, Chen YC, Chen YW, Chiu TH, Kuo YT, Chen CH. Far-infrared radiation prevents decline in β-cell mass and function in diabetic mice via the mitochondria-mediated Sirtuin1 pathway. Metabolism 2020; 104:154143. [PMID: 31927009 DOI: 10.1016/j.metabol.2020.154143] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 12/30/2019] [Accepted: 01/08/2020] [Indexed: 12/11/2022]
Abstract
Insulin deficiency in type 2 diabetes mellitus (DM) involves a decline in both pancreatic β-cell mass and function. Enhancing β-cell preservation represents an important therapeutic strategy to treat type 2 DM. Far-infrared (FIR) radiation has been found to induce promyelocytic leukemia zinc finger protein (PLZF) activation to protect the vascular endothelium in diabetic mice. The influence of FIR on β-cell preservation is unknown. Our previous study reveals that the biologically effective wavelength of FIR is 8-10 μm. In the present study, we investigated the biological effects of FIR (8-10 μm) on both survival and insulin secretion function of β-cells. FIR reduced pancreatic islets loss and increased insulin secretion in nicotinamide-streptozotocin-induced DM mice, but only promoted insulin secretion in DM PLZF-/- mice. FIR-upregulated PLZF to induce an anti-apoptotic effect in a β cell line RIN-m5f. FIR also upregulated mitochondrial function and the ratio of NAD+/NADH, and then induced Sirtuin1 (Sirt1) expression. The mitochondria Complex I inhibitor rotenone blocked FIR-induced PLZF and Sirt1. The Sirt1 inhibitor EX527 and Sirt1 siRNA inhibited FIR-induced PLZF and insulin respectively. Sirt1 upregulation also increased CaV1.2 expression and calcium influx that promotes insulin secretion in β-cells. In summary, FIR-enhanced mitochondrial function prevents β-cell apoptosis and enhances insulin secretion in DM mice through the Sirt1 pathway.
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Affiliation(s)
- Yung-Ho Hsu
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan
| | - Yen-Cheng Chen
- Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Yu-Wei Chen
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan
| | - Tzu-Hsuan Chiu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan
| | - Yung-Ting Kuo
- Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taiwan
| | - Cheng-Hsien Chen
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan; Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan.
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