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Raj JAT, Shah J, Ghanekar S, John G, Goda JS, Chatterjee A. Pharmacological and therapeutic innovation to mitigate radiation-induced cognitive decline (RICD) in brain tumor patients. Cancer Lett 2025; 620:217700. [PMID: 40194653 DOI: 10.1016/j.canlet.2025.217700] [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: 12/30/2024] [Revised: 04/01/2025] [Accepted: 04/04/2025] [Indexed: 04/09/2025]
Abstract
Radiation therapy is a key treatment modality in both primary and metastatic brain tumors. However, despite its efficacy, it often results in cognitive decline, particularly after whole brain RT (WBRT). Radiation-induced cognitive impairment, which affects memory, attention, and executive function, significantly affects Quality Of Life (QOL) and functional independence. Although white matter necrosis, a hallmark of conventional radiation techniques, has become less common with modern methods, cognitive deficits remain a persistent issue. Neuroinflammation is a key driver of this decline, along with disruptions in hippocampal neurogenesis and damage to regions of the brain. Radiation affects neural stem cells, mature neurons, and glial cells, particularly within the hippocampus, affecting cognition. Recent studies suggest that targeting neuroinflammation and other key Signaling pathways (NMDAR, RAAS, PARP, PPAR, etc.) can reduce cognitive impairment. This review examines the theme of radiation-induced cognitive decline and explores possible interventions to prevent or mitigate these outcomes.
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Affiliation(s)
- Jemema Agnes Tripena Raj
- Department of Radiation Oncology and Radiobiology Lab, Advance Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Center, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, India
| | - Janmey Shah
- Department of Radiation Oncology and Radiobiology Lab, Advance Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Center, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, India
| | - Shubham Ghanekar
- Department of Radiation Oncology and Radiobiology Lab, Advance Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Center, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, India
| | - Geofrey John
- Department of Radiation Oncology and Radiobiology Lab, Advance Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Center, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, India
| | - Jayant S Goda
- Department of Radiation Oncology and Radiobiology Lab, Advance Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Center, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, India
| | - Abhishek Chatterjee
- Department of Radiation Oncology and Radiobiology Lab, Advance Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Center, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, India.
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Sang P, Ma Y, Zhang X, Chen B, He F, Shen N, Zhao J. BMAL1 attenuates intervertebral disc degeneration by activating the SIRT1/PGC-1α pathway: evidence from vitro studies. Sci Rep 2025; 15:9651. [PMID: 40113885 PMCID: PMC11926130 DOI: 10.1038/s41598-025-94029-7] [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: 07/13/2024] [Accepted: 03/11/2025] [Indexed: 03/22/2025] Open
Abstract
To explore the potential effects and the corresponding mechanisms of brain and muscle arnt-like protein-1 (BMAL1) on the progression of intervertebral disc degeneration (IVDD) in vitro studies. The expression of BMAL1, SIRT1 and PINK1 were evaluated by the method of siRNA/pcDNA in the immortalized nucleus pulposus (NP) cells. The expression of SIRT1/PGC-1α pathway was assessed. The characteristics of NP cell, containing the activity and density, the level of apoptosis, inflammatory response, reactive oxygen species (ROS), senescence, and mitophagy were evaluated. The overexpression of BMAL1 was achieved with the pcDNA3.1, the expression of SIRT1 and PGC-1α were increased, the inflammatory response, the ROS, the level of apoptosis and senescence were decreased, however, the level of mitophagy, the activity and density of NP cell were enhanced. The BMAL1 inhibites the progression of IVDD by activating the SIRT1/PGC-1α pathway in the vitro studies.
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Affiliation(s)
- Peiming Sang
- Ningbo Medical Center LiHuiLi Hospital, Ningbo, Zhejiang, People's Republic of China
- The Affiliated LiHuiLi Hospital of Ningbo University, #57, Xingning Road, Yinzhou District, Ningbo, Zhejiang, People's Republic of China
| | - Yanyan Ma
- Ningbo Medical Center LiHuiLi Hospital, Ningbo, Zhejiang, People's Republic of China.
- The Affiliated LiHuiLi Hospital of Ningbo University, #57, Xingning Road, Yinzhou District, Ningbo, Zhejiang, People's Republic of China.
| | - Xie Zhang
- Ningbo Medical Center LiHuiLi Hospital, Ningbo, Zhejiang, People's Republic of China
- The Affiliated LiHuiLi Hospital of Ningbo University, #57, Xingning Road, Yinzhou District, Ningbo, Zhejiang, People's Republic of China
| | - Binhui Chen
- Ningbo Medical Center LiHuiLi Hospital, Ningbo, Zhejiang, People's Republic of China
- The Affiliated LiHuiLi Hospital of Ningbo University, #57, Xingning Road, Yinzhou District, Ningbo, Zhejiang, People's Republic of China
| | - Fan He
- Ningbo Medical Center LiHuiLi Hospital, Ningbo, Zhejiang, People's Republic of China
- The Affiliated LiHuiLi Hospital of Ningbo University, #57, Xingning Road, Yinzhou District, Ningbo, Zhejiang, People's Republic of China
| | - Neng Shen
- The NO. 3 Hospital of Yinzhou District, Ningbo, Zhejiang, People's Republic of China
| | - Jiangang Zhao
- The NO. 4 Hospital of Yuyao District, Ningbo, Zhejiang, People's Republic of China
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Tan Q. The Beneficial Effects of Combined Exercise and Polyphenols in Alzheimer's Disease. Phytother Res 2025; 39:1020-1034. [PMID: 39716920 DOI: 10.1002/ptr.8422] [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: 04/21/2024] [Revised: 11/16/2024] [Accepted: 12/10/2024] [Indexed: 12/25/2024]
Abstract
Regular exercise enhances life quality, lowers the risk of cognitive damage, and slows the advancement of Alzheimer's disease (AD). Natural compounds rich in polyphenols have garnered attention as a non-pharmacological means of treating and preventing AD. The primary component of wine, grape seeds, and nuts is polyphenols. Research suggests that polyphenols slow down the rate of neurodegeneration in AD and lessen learning impairment. Furthermore, polyphenols lessen brain impairments related to cognition. Additionally, polyphenols can specifically restructure amyloid-β (Aβ) structures and soluble oligomers into non-toxic alternative species. They have also been revealed to increase brain-derived neurotrophic factors expression, suggesting that they have a positive impact on the creation of neurotrophins. The benefits of polyphenol supplementation and exercise, which can both provide neuroprotection, have not been well studied in AD patients. This review aimed to investigate the effects of combined exercise polyphenols on inflammation, neuroprotection, several conformational toxic species of Aβ, and Aβ-induced apoptosis in AD.
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Affiliation(s)
- Qinghua Tan
- Graduate School of Education in Physical Education, Sangmyung University, Seoul, Korea
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Ben Dassi R, Ibidhi S, Jemai H, Cherif A, Driouich Chaouachi R. Resveratrol: Challenges and prospects in extraction and hybridization with nanoparticles, polymers, and bio-ceramics. Phytother Res 2024; 38:5309-5322. [PMID: 39228146 DOI: 10.1002/ptr.8319] [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: 01/19/2024] [Revised: 07/17/2024] [Accepted: 07/30/2024] [Indexed: 09/05/2024]
Abstract
Resveratrol (RSV), a bioactive natural phenolic compound found in plants, fruits, and vegetables, has garnered significant attention in pharmaceutical, food, and cosmetic industries due to its remarkable biological and pharmacological activities. Despite its potential in treating various diseases, its poor pharmacokinetic properties, such as low solubility, stability, bioavailability, and susceptibility to rapid oxidation, limit its biomedical applications. Recent advancements focus on incorporating resveratrol into innovative materials like nanoparticles, polymers, and bio-ceramics to enhance its properties and bioavailability. In this review, an exhaustive literature search was conducted from PubMed, Google Scholar, Science Direct, Scopus, and Web of Science databases to explore these advancements, to compares conventional and innovative extraction methods, and to highlights resveratrol's therapeutic potential, including its anti-inflammatory, anti-oxidative, anti-cancerogenic, antidiabetic, neuroprotective, and cardio-protective properties. Additionally, we discuss the challenges and prospects of hybrid materials combining resveratrol with nanoparticles, polymers, and bio-ceramics for therapeutic applications. Rigorous studies are still needed to confirm their clinical efficacy.
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Affiliation(s)
- Roua Ben Dassi
- Laboratory BVBGR-LR11ES31, Institute of Biotechnology of Sidi Thabet, University of Manouba, Tunisia
- Doctoral School in Sciences and Technologies of Computing, Communications, Design and the Environment, University of Manouba, Tunisia
| | - Salah Ibidhi
- Laboratory BVBGR-LR11ES31, Institute of Biotechnology of Sidi Thabet, University of Manouba, Tunisia
- Doctoral School in Sciences and Technologies of Computing, Communications, Design and the Environment, University of Manouba, Tunisia
| | - Hedya Jemai
- Laboratory BVBGR-LR11ES31, Institute of Biotechnology of Sidi Thabet, University of Manouba, Tunisia
| | - Ameur Cherif
- Laboratory BVBGR-LR11ES31, Institute of Biotechnology of Sidi Thabet, University of Manouba, Tunisia
| | - Rim Driouich Chaouachi
- Laboratory BVBGR-LR11ES31, Institute of Biotechnology of Sidi Thabet, University of Manouba, Tunisia
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Pirmoradi Z, Nakhaie M, Ranjbar H, Kalantar-Neyestanaki D, Kohlmeier KA, Asadi-Shekaari M, Hassanshahi A, Shabani M. Resveratrol and 1,25-dihydroxyvitamin D decrease Lingo-1 levels, and improve behavior in harmaline-induced Essential tremor, suggesting potential therapeutic benefits. Sci Rep 2024; 14:9864. [PMID: 38684734 PMCID: PMC11058818 DOI: 10.1038/s41598-024-60518-4] [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: 11/24/2023] [Accepted: 04/24/2024] [Indexed: 05/02/2024] Open
Abstract
Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.
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Affiliation(s)
- Zeynab Pirmoradi
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran
| | - Mohsen Nakhaie
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Hoda Ranjbar
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran
| | | | - Kristi A Kohlmeier
- Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Majid Asadi-Shekaari
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran
| | - Amin Hassanshahi
- Department of Physiology, Medical School, Bam University of Medical Sciences, Bam, Iran
| | - Mohammad Shabani
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran.
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Sharma N, Kumar P, Shukla KS, Maheshwari S. AGE RAGE Pathways: Cardiovascular Disease and Oxidative Stress. Drug Res (Stuttg) 2023; 73:408-411. [PMID: 37308093 DOI: 10.1055/a-2047-3896] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
It is well established that Advanced Glycation End Products (AGEs) and their receptor (RAGE) are primarily responsible for the development of cardiovascular disease. As a result, diabetic therapy is very interested in therapeutic strategies that can target the AGE-RAGE axis. The majority of the AGE-RAGE inhibitors showed encouraging outcomes in animal experiments, but more information is needed to completely understand their clinical effects. The main mechanism implicated in the aetiology of cardiovascular disease in people with diabetes is oxidative stress and inflammation mediated by AGE-RAGE interaction. Numerous PPAR-agonists have demonstrated favourable outcomes in the treatment of cardio-metabolic illness situations by inhibiting the AGE-RAGE axis. The body's ubiquitous phenomena of inflammation occur in reaction to environmental stressors such tissue damage, infection by pathogens, or exposure to toxic substances. Rubor (redness), calor (heat), tumour (swelling), colour (pain), and in severe cases, loss of function, are its cardinal symptoms. When exposed, the lungs develop silicotic granulomas with the synthesis of collagen and reticulin fibres. A natural flavonoid called chyrsin has been found to have PPAR-agonist activity as well as antioxidant and anti-inflammatory properties. The RPE insod2+/animals underwent mononuclear phagocyte-induced apoptosis, which was accompanied with decreased superoxide dismutase 2 (SOD2) and increased superoxide generation. Injections of the serine proteinase inhibitor SERPINA3K decreased proinflammatory factor expression in mice with oxygen-induced retinopathy, decreased ROS production, and increased levels of SOD and GSH.
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Affiliation(s)
- Neeraj Sharma
- Department of Pharmacy, Bhagwant University, Ajmer, India
| | - Pavan Kumar
- Ph.D scholar of Department of Pharmacy, Bhagwant University, Ajmer, India
| | | | - Shubhrat Maheshwari
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Rama University, Kanpur, Uttar Pradesh, India
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Liu Y, Yang H, Luo N, Fu Y, Qiu F, Pan Z, Li X, Jian W, Yang X, Xue Q, Luo Y, Yu B, Liu Z. An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway. J Transl Med 2023; 21:486. [PMID: 37475042 PMCID: PMC10360347 DOI: 10.1186/s12967-023-04345-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 07/11/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Sepsis-associated encephalopathy (SAE) is characterized by diffuse brain dysfunction, long-term cognitive impairment, and increased morbidity and mortality. The current treatment for SAE is mainly symptomatic; the lack of specific treatment options and a poor understanding of the underlying mechanism of disease are responsible for poor patient outcomes. Fgr is a member of the Src family of tyrosine kinases and is involved in the innate immune response, hematologic cancer, diet-induced obesity, and hemorrhage-induced thalamic pain. This study investigated the protection provided by an Fgr kinase inhibitor in SAE and the underlying mechanism(s) of action. METHODS A cecal ligation and puncture (CLP)-induced mouse sepsis model was established. Mice were treated with or without an Fgr inhibitor and a PGC-1α inhibitor/activator. An open field test, a novel object recognition test, and an elevated plus maze were used to assess neurobehavioral changes in the mice. Western blotting and immunofluorescence were used to measure protein expression, and mRNA levels were measured using quantitative PCR (qPCR). An enzyme-linked immunosorbent assay was performed to quantify inflammatory cytokines. Mitochondrial membrane potential and morphology were measured by JC-1, electron microscopy, and the MitoTracker Deep Red probe. Oxidative stress and mitochondrial dysfunction were analyzed. In addition, the regulatory effect of Fgr on sirtuin 1 (SIRT1) was assessed. RESULTS CLP-induced sepsis increased the expression of Fgr in the hippocampal neurons. Pharmacological inhibition of Fgr attenuated CLP-induced neuroinflammation, the survival rate, cognitive and emotional dysfunction, oxidative stress, and mitochondrial dysfunction. Moreover, Fgr interacted with SIRT1 and reduced its activity and expression. In addition, activation of SIRT1/PGC-1α promoted the protective effects of the Fgr inhibitor on CLP-induced brain dysfunction, while inactivation of SIRT1/PGC-1α counteracted the benefits of the Fgr inhibitor. CONCLUSIONS To our knowledge, this is the first report of Fgr kinase inhibition markedly ameliorating SAE through activation of the SIRT1/PGC-1α pathway, and this may be a promising therapeutic target for SAE.
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Affiliation(s)
- Yuqiang Liu
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
| | - Han Yang
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Nanbo Luo
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Yifei Fu
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Fang Qiu
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Burn and Plastic Surgery, Shenzhen Longhua District Central Hospital, Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, Guangdong, China
| | - Zhenglong Pan
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Xiongjuan Li
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Wenling Jian
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Xinping Yang
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Qingsheng Xue
- Department of Anesthesiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Yan Luo
- Department of Anesthesiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Buwei Yu
- Department of Anesthesiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Zhiheng Liu
- Department of Anesthesiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
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Suriyaprom S, Srisai P, Intachaisri V, Kaewkod T, Pekkoh J, Desvaux M, Tragoolpua Y. Antioxidant and Anti-Inflammatory Activity on LPS-Stimulated RAW 264.7 Macrophage Cells of White Mulberry ( Morus alba L.) Leaf Extracts. Molecules 2023; 28:molecules28114395. [PMID: 37298871 DOI: 10.3390/molecules28114395] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
The white mulberry (Morus alba L.) is widely used as a medicinal plant in Asia. In this study, the bioactive compounds of ethanolic extracts of white mulberry leaves from the Sakon Nakhon and Buriram cultivars were evaluated. The ethanolic extracts of mulberry leaves from the Sakon Nakhon cultivar showed the highest total phenolic content of 49.68 mg GAE/g extract and antioxidant activities of 4.38 mg GAE/g extract, 4.53 mg TEAC/g extract, and 92.78 mg FeSO4/g extract using 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,20-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays, respectively. The resveratrol and oxyresveratrol compounds in mulberry leaves were also investigated by high-performance liquid chromatography (HPLC). The mulberry leaf extracts from the Sakon Nakhon and Buriram cultivars showed oxyresveratrol contents of 1.20 ± 0.04 mg/g extract and 0.39 ± 0.02 mg/g extract, respectively, whereas resveratrol was not detected. It was also found that the potent anti-inflammatory properties of mulberry leaf extracts and its compounds, resveratrol and oxyresveratrol, suppressed the LPS-stimulated inflammatory responses in RAW 264.7 macrophage cells by significantly reducing nitric oxide production in a concentration-dependent manner. These compounds further inhibited interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production and suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophage cells. Therefore, it is established that mulberry leaf extract and its bioactive compounds contribute to its anti-inflammatory activity.
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Affiliation(s)
- Sureeporn Suriyaprom
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand
- INRAE, UCA, UMR0454 MEDIS, 63000 Clermont-Ferrand, France
| | | | - Varachaya Intachaisri
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Thida Kaewkod
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Natural Extracts and Innovative Products for Alternative Healthcare Research Group, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Jeeraporn Pekkoh
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
| | | | - Yingmanee Tragoolpua
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Natural Extracts and Innovative Products for Alternative Healthcare Research Group, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
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Prades-Sagarra È, Yaromina A, Dubois LJ. Polyphenols as Potential Protectors against Radiation-Induced Adverse Effects in Patients with Thoracic Cancer. Cancers (Basel) 2023; 15:cancers15092412. [PMID: 37173877 PMCID: PMC10177176 DOI: 10.3390/cancers15092412] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
Radiotherapy is one of the standard treatment approaches used against thoracic cancers, occasionally combined with chemotherapy, immunotherapy and molecular targeted therapy. However, these cancers are often not highly sensitive to standard of care treatments, making the use of high dose radiotherapy necessary, which is linked with high rates of radiation-induced adverse effects in healthy tissues of the thorax. These tissues remain therefore dose-limiting factors in radiation oncology despite recent technological advances in treatment planning and delivery of irradiation. Polyphenols are metabolites found in plants that have been suggested to improve the therapeutic window by sensitizing the tumor to radiotherapy, while simultaneously protecting normal cells from therapy-induced damage by preventing DNA damage, as well as having anti-oxidant, anti-inflammatory or immunomodulatory properties. This review focuses on the radioprotective effect of polyphenols and the molecular mechanisms underlying these effects in the normal tissue, especially in the lung, heart and esophagus.
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Affiliation(s)
- Èlia Prades-Sagarra
- The M-Lab, Department of Precision Medicine, GROW-School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Ala Yaromina
- The M-Lab, Department of Precision Medicine, GROW-School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Ludwig J Dubois
- The M-Lab, Department of Precision Medicine, GROW-School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands
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10
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Xie D, Huang Q, Zhou P. Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation. Int J Mol Sci 2023; 24:ijms24087656. [PMID: 37108815 PMCID: PMC10142602 DOI: 10.3390/ijms24087656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 04/07/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
DNA damage in astronauts induced by cosmic radiation poses a major barrier to human space exploration. Cellular responses and repair of the most lethal DNA double-strand breaks (DSBs) are crucial for genomic integrity and cell survival. Post-translational modifications (PTMs), including phosphorylation, ubiquitylation, and SUMOylation, are among the regulatory factors modulating a delicate balance and choice between predominant DSB repair pathways, such as non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we focused on the engagement of proteins in the DNA damage response (DDR) modulated by phosphorylation and ubiquitylation, including ATM, DNA-PKcs, CtIP, MDM2, and ubiquitin ligases. The involvement and function of acetylation, methylation, PARylation, and their essential proteins were also investigated, providing a repository of candidate targets for DDR regulators. However, there is a lack of radioprotectors in spite of their consideration in the discovery of radiosensitizers. We proposed new perspectives for the research and development of future agents against space radiation by the systematic integration and utilization of evolutionary strategies, including multi-omics analyses, rational computing methods, drug repositioning, and combinations of drugs and targets, which may facilitate the use of radioprotectors in practical applications in human space exploration to combat fatal radiation hazards.
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Affiliation(s)
- Dafei Xie
- Department of Radiation Biology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Taiping Road 27th, Haidian District, Beijing 100850, China
| | - Qi Huang
- Department of Radiation Biology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Taiping Road 27th, Haidian District, Beijing 100850, China
- Department of Preventive Medicine, School of Public Health, University of South China, Changsheng West Road 28th, Zhengxiang District, Hengyang 421001, China
| | - Pingkun Zhou
- Department of Radiation Biology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Taiping Road 27th, Haidian District, Beijing 100850, China
- Department of Preventive Medicine, School of Public Health, University of South China, Changsheng West Road 28th, Zhengxiang District, Hengyang 421001, China
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Liu H, An ZY, Li ZY, Yang LH, Zhang XL, Lv YT, Yin XJ, Quan LH, Kang JD. The ginsenoside Rh2 protects porcine oocytes against aging and oxidative stress by regulating SIRT1 expression and mitochondrial activity. Theriogenology 2023; 200:125-135. [PMID: 36805249 DOI: 10.1016/j.theriogenology.2023.02.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/25/2023] [Accepted: 02/07/2023] [Indexed: 02/11/2023]
Abstract
Post-ovulatory aging, a major problem faced by oocytes cultured in vitro, causes oxidative damage and mitochondrial dysfunction in oocytes. The ginsenoside Rh2 is one of the main monomeric components of ginseng, but its effects on porcine oocytes are unknown. In the present study, in vitro aging (IVA) and accelerated induction of aging using H2O2 resulted in DNA damage and an increased incidence of abnormal spindle formation in porcine oocytes. Rh2 supplementation increased the antioxidant capacity, reduced the occurrence of early apoptosis, and improved the development of in vitro fertilized blastocysts. It also rescued the abnormal aggregation of mitochondria and the decrease of the mitochondrial membrane potential under mitochondrial dysfunction. Meanwhile, Rh2 enhanced mRNA expression of the anti-aging and mitochondrial biogenesis-related genes silent information regulator of transcription 1 (SIRT1) and peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), and the antioxidant gene superoxide dismutase 1 (SOD1). The protection of porcine oocytes against aging and oxidative stress by Rh2 was confirmed using the SIRT1-specific inhibitor EX-527. Our results reveal that Rh2 upregulates SIRT1/PGC-1α to enhance mitochondrial function in porcine oocytes and improve their quality. Our study indicates that Rh2 can be used to prevent mitochondrial dysfunction in oocytes.
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Affiliation(s)
- Hongye Liu
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China.
| | - Zhi-Yong An
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China.
| | - Zhou-Yan Li
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China.
| | - Liu-Hui Yang
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China.
| | - Xiu-Li Zhang
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China.
| | - Yan-Tong Lv
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China.
| | - Xi-Jun Yin
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China; Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanji, 133002, China.
| | - Lin-Hu Quan
- College of Pharmacy, Yanbian University, Yanji, 133002, China.
| | - Jin-Dan Kang
- Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China; Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanji, 133002, China.
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Abstract
Neurofibrillary tangles and plaques containing tau serve as the biological markers for Alzheimer disease (AD) and pathogenesis is widely believed to be driven by the production and deposition of the β-amyloid peptide (Aβ). The β-amyloid peptide (Aβ) that results from the modification of the amyloid precursor protein (APP) by builds up as amyloid deposits in neuronal cells. Thus, a protein misfolding process is involved in the production of amyloid. In a native, aqueous buffer, amyloid fibrils are usually exceedingly stable and nearly insoluble. Although amyloid is essentially a foreign substance made of self-proteins, the immune system has difficulty identifying and eliminating it as such for unknown reasons. While the amyloidal deposit may have a direct role in the disease mechanism in some disease states involving amyloidal deposition, this is not always the case. Current research has shown that PS1 (presenilin 1) and BACE (beta-site APP-cleaving enzyme) have - and -secretase activity that increases β-amyloid peptide (Aβ). Wealth of data has shown that oxidative stress and AD are closely connected that causes the death of neuronal cells by producing reactive oxygen species (ROS). Additionally, it has been demonstrated that advanced glycation end products (AGEs) and β-amyloidal peptide (Aβ) together increase neurotoxicity. The objective of this review is to compile the most recent and intriguing data of AGEs and receptor for advanced glycation end products (RAGE) pathways which are responsible for AD.
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Affiliation(s)
- Shubhrat Maheshwari
- Faculty of Pharmaceutical Sciences, Rama University, Kanpur, Uttar Pradesh, India
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Singh A, Ansari VA, Mahmood T, Ahsan F, Wasim R, Shariq M, Parveen S, Maheshwari S. Receptor for Advanced Glycation End Products: Dementia and Cognitive Impairment. Drug Res (Stuttg) 2023. [PMID: 36889338 DOI: 10.1055/a-2015-8041] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/10/2023]
Abstract
The pathophysiological processes of dementia and cognitive impairment are linked to advanced glycation end products (AGEs) and their receptor (RAGE).The neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau protein and senile plaques (SPs), which are brought on by amyloid beta (Aβ) deposition, are the hallmarks of Alzheimer's disease (AD), a progressive neurodegenerative condition. Advanced glycation end products that are produced as a result of vascular dysfunction are bound by the receptor for advanced glycation end products (RAGE). Dementia and cognitive impairment could develop when RAGE binds to Aβ and produces reactive oxygen species, aggravating Aβ buildup and ultimately resulting in SPs and NFTs. RAGE could be a more powerful biomarker than Aβ because it is implicated in early AD. The resident immune cells in the brain known as microglia are essential for healthy brain function. Microglia is prominent in the amyloid plaques' outside border as well as their central region in Alzheimer's disease. Microglial cells, in the opinion of some authors, actively contribute to the formation of amyloid plaques. In this review, we first discuss the early diagnosis of dementia and cognitive impairment, and then detail the interaction between RAGE and Aβ and Tau that is necessary to cause dementia and cognitive impairment pathology, and it is anticipated that the creation of RAGE probes will help in the diagnosis and treatment of dementia and cognitive impairment.
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Affiliation(s)
- Aditya Singh
- Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Vaseem Ahamad Ansari
- Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Tarique Mahmood
- Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Farogh Ahsan
- Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Rufaida Wasim
- Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Mohammad Shariq
- Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Saba Parveen
- Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India
| | - Shubhrat Maheshwari
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Rama University, Mandhana, Bithoor Road, Kanpur, Uttar Pradesh, India
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Therapeutic potential of natural molecules against Alzheimer's disease via SIRT1 modulation. Biomed Pharmacother 2023; 161:114474. [PMID: 36878051 DOI: 10.1016/j.biopha.2023.114474] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/01/2023] [Accepted: 03/02/2023] [Indexed: 03/06/2023] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease mainly characterized by progressive cognitive dysfunction and memory impairment. Recent studies have shown that regulating silent information regulator 1 (SIRT1) expression has a significant neuroprotective effect, and SIRT1 may become a new therapeutic target for AD. Natural molecules are an important source of drug development for use in AD therapy and may regulate a wide range of biological events by regulating SIRT1 as well as other SIRT1-mediated signaling pathways. This review aims to summarize the correlation between SIRT1 and AD and to identify in vivo and in vitro studies investigating the anti-AD properties of natural molecules as modulators of SIRT1 and SIRT1-mediated signaling pathways. A literature search was conducted for studies published between January 2000 and October 2022 using various literature databases, including Web of Science, PubMed, Google Scholar, Science Direct, and EMBASE. Natural molecules, such as resveratrol, quercetin, icariin, bisdemethoxycurcumin, dihydromyricetin, salidroside, patchouli, sesamin, rhein, ligustilide, tetramethoxyflavanone, 1-theanine, schisandrin, curcumin, betaine, pterostilbene, ampelopsin, schisanhenol, and eriodictyol, have the potential to modulate SIRT1 and SIRT1 signaling pathways, thereby combating AD. The natural molecules modulating SIRT1 discussed in this review provide a potentially novel multi-mechanistic therapeutic strategy for AD. However, future clinical trials need to be conducted to further investigate their beneficial properties and to determine the safety and efficacy of SIRT1 natural activators against AD.
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15
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Javadi A, Nikhbakht MR, Ghasemian Yadegari J, Rustamzadeh A, Mohammadi M, Shirazinejad A, Azadbakht S, Abdi Z. In-vivo and in vitro assessments of the radioprotective potential natural and chemical compounds: a review. Int J Radiat Biol 2023; 99:155-165. [PMID: 35549605 DOI: 10.1080/09553002.2022.2078007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE The study of the radioactive role of natural and chemical substances on human and animal studies has been the subject of research by some researchers. Therefore, the review of some of the past and current studies conducted in this field, can provide helpful information to elucidate of the importance of radioprotective components in reducing radiation exposure side effects. METHODS The authors search for keywords including In vitro, In vivo, Radioprotective, Ionizing radiation, and Vitamin in ScienceDirect, Scopus, Pubmed, and Google Scholar databases to access previously published articles and search for more reference articles on the role of radioprotective materials from natural and chemical compounds. RESULTS Radiation exposure can produce reactive oxygen species (ROS) in the body, however most of which are eliminated by the body's natural mechanisms, but when the body's antioxidant systems do not have enough ability to neutralize free radicals, oxidative stress occurs, which causes damage to DNA and body tissues. Therefore, it is necessary use of alternative substances that reduce and inhibit free radicals. CONCLUSION In general, recommended that antioxidant component(s) can be protect tissue damages in humans or animals, due to the their ability to scavenge free radicals generated by ionizing radiation.
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Affiliation(s)
- Anis Javadi
- Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Mohammad Reza Nikhbakht
- Department of Physiology and Pharmacology, School of Medicine Medicinal Plants Research Center Yasuj, University of Medical Sciences, Yasuj, Iran
| | - Javad Ghasemian Yadegari
- Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Auob Rustamzadeh
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Mohammadi
- Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran.,Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.,Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Alireza Shirazinejad
- Department of Food Science and Technology, Sarvestan Branch, Islamic Azad University, Sarvestan, Iran
| | - Saleh Azadbakht
- Department of Internal Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Zahra Abdi
- Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
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Mitra S, Dash R, Sohel M, Chowdhury A, Munni YA, Ali C, Hannan MA, Islam T, Moon IS. Targeting Estrogen Signaling in the Radiation-induced Neurodegeneration: A Possible Role of Phytoestrogens. Curr Neuropharmacol 2023; 21:353-379. [PMID: 35272592 PMCID: PMC10190149 DOI: 10.2174/1570159x20666220310115004] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/01/2022] [Accepted: 03/06/2022] [Indexed: 11/22/2022] Open
Abstract
Radiation for medical use is a well-established therapeutic method with an excellent prognosis rate for various cancer treatments. Unfortunately, a high dose of radiation therapy comes with its own share of side effects, causing radiation-induced non-specific cellular toxicity; consequently, a large percentage of treated patients suffer from chronic effects during the treatment and even after the post-treatment. Accumulating data evidenced that radiation exposure to the brain can alter the diverse cognitive-related signaling and cause progressive neurodegeneration in patients because of elevated oxidative stress, neuroinflammation, and loss of neurogenesis. Epidemiological studies suggested the beneficial effect of hormonal therapy using estrogen in slowing down the progression of various neuropathologies. Despite its primary function as a sex hormone, estrogen is also renowned for its neuroprotective activity and could manage radiation-induced side effects as it regulates many hallmarks of neurodegenerations. Thus, treatment with estrogen and estrogen-like molecules or modulators, including phytoestrogens, might be a potential approach capable of neuroprotection in radiation-induced brain degeneration. This review summarized the molecular mechanisms of radiation effects and estrogen signaling in the manifestation of neurodegeneration and highlighted the current evidence on the phytoestrogen mediated protective effect against radiationinduced brain injury. This existing knowledge points towards a new area to expand to identify the possible alternative therapy that can be taken with radiation therapy as adjuvants to improve patients' quality of life with compromised cognitive function.
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Affiliation(s)
- Sarmistha Mitra
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju38066, Republic of Korea
| | - Raju Dash
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju38066, Republic of Korea
| | - Md. Sohel
- Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail-1902, Bangladesh
| | - Apusi Chowdhury
- Department of Pharmaceutical Science, North-South University, Dhaka-12 29, Bangladesh
| | - Yeasmin Akter Munni
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju38066, Republic of Korea
| | - Chayan Ali
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala SE-751 08, Sweden
| | - Md. Abdul Hannan
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Tofazzal Islam
- Institute of Biotechnology and Genetic Engineering (IBGE), Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU), Gazipur, Bangladesh
| | - Il Soo Moon
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju38066, Republic of Korea
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Jit BP, Pattnaik S, Arya R, Dash R, Sahoo SS, Pradhan B, Bhuyan PP, Behera PK, Jena M, Sharma A, Agrawala PK, Behera RK. Phytochemicals: A potential next generation agent for radioprotection. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 106:154188. [PMID: 36029645 DOI: 10.1016/j.phymed.2022.154188] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 03/13/2022] [Accepted: 05/17/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Radiation hazards are accountable for extensive damage in the biological system and acts as a public health burden. Owing to the rapid increasing in radiation technology, both Ionizing radiation (IR) from natural and man made source poses detrimental outcome to public health. IR releases free radicals which induces oxidative stress and deleterious biological damage by modulating radiation induced signalling intermediates. The efficacy of existing therapeutic approach and treatment strategy are limited owing to their toxicity and associated side effects. Indian system of traditional medicine is enriched with prospective phytochemicals with potential radioprotection ability. PURPOSE The present review elucidated and summarized the potential role of plant derived novel chemical compound with prospective radioprotective potential. METHOD So far as the traditional system of Indian medicine is concerned, plant kingdom is enriched with potential bioactive molecules with diverse pharmacological activities. We reviewed several compounds mostly secondary metabolites from plant origin using various search engines. RESULTS Both compounds from land plants and marine source exhibited antioxidant antiinflammatory, free radical scavenging ability. These compounds have tremendous potential in fine-tuning of several signalling intermediates, which are actively participated in the progression and development of a pathological condition associated with radiation stress. CONCLUSION Development and explore of an operational radioprotective agent from originated from plant source that can be used as a novel molecular tool to eliminate the widespread damage caused by space exploration, ionizing radiation, nuclear war and radiotherapy has been significantly appreciated. Through extensive literature search we highlighted several compounds from both land plant and marine origin can be implemented for a better therapeutic potential against radiation induced injury. Furthermore, extensive clinical trials must be carried out in near future for better therapeutic modality and clinical efficacy.
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Affiliation(s)
- Bimal Prasad Jit
- Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India; School of Life Sciences, Sambalpur University, Jyoti Vihar, Burla 768019, India
| | - Subhaswaraj Pattnaik
- Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Centre of Excellence in Natural Products and Therapeutics, Department of Biotechnology and Bioinformatics, Sambalpur University, Jyoti Vihar, Burla, Odisha 768019, India
| | - Rakesh Arya
- Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India; School of Life Sciences, Sambalpur University, Jyoti Vihar, Burla 768019, India
| | - Rutumbara Dash
- Departement of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
| | | | - Biswajita Pradhan
- Algal Biotechnology and Molecular Systematic Laboratory, Post Graduate Department of Botany, Berhampur University, Bhanja Bihar, Berhampur, Odisha 760007, India; Department of Biotechnology, Sangmyung University, Seoul 03016, South Korea
| | - Prajna Paramita Bhuyan
- Department of Botany, Maharaja Sriram Chandra Bhanja Deo University, Baripada, Odisha 757003, India
| | - Pradyota Kumar Behera
- Department of Chemistry, Berhampur University, Bhanja Bihar, Berhampur, Odisha 760007, India
| | - Mrutyunjay Jena
- Algal Biotechnology and Molecular Systematic Laboratory, Post Graduate Department of Botany, Berhampur University, Bhanja Bihar, Berhampur, Odisha 760007, India
| | - Ashok Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
| | - Paban Kumar Agrawala
- Institute of Nuclear Medicine and Allied Science, Defence Research and Development Organization, New Delhi 110054, India
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Fabres RB, Nunes RR, de Medeiros de Mattos M, Andrade MKG, Martini APR, Tassinari ID, Sanches EF, de Fraga LS, Netto CA. Therapeutic hypothermia for the treatment of neonatal hypoxia-ischemia: sex-dependent modulation of reactive astrogliosis. Metab Brain Dis 2022; 37:2315-2329. [PMID: 35778625 DOI: 10.1007/s11011-022-01030-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 06/09/2022] [Indexed: 11/26/2022]
Abstract
Therapeutic hypothermia (TH) is the standard treatment for neonatal hypoxia-ischemia (HI) with a time window limited up to 6 h post injury. However, influence of sexual dimorphism in the therapeutic window for TH has not yet been elucidated in animal models of HI. Therefore, the aim of this study was to investigate the most effective time window to start TH in male and female rats submitted to neonatal HI. Wistar rats (P7) were divided into the following groups: NAÏVE and SHAM (control groups), HI (submitted to HI) and TH (submitted to HI and TH; 32ºC for 5 h). TH was started at 2 h (TH-2 h group), 4 h (TH-4 h group), or 6 h (TH-6 h group) after HI. At P14, animals were subjected to behavioural tests, volume of lesion and reactive astrogliosis assessments. Male and female rats from the TH-2 h group showed reduction in the latency of behavioral tests, and decrease in volume of lesion and intensity of GFAP immunofluorescence. TH-2 h females also showed reduction of degenerative cells and morphological changes in astrocytes. Interestingly, females from the TH-6 h group showed an increase in volume of lesion and in number of degenerative hippocampal cells, associated with worse behavioral performance. Together, these results indicate that TH neuroprotection is time- and sex-dependent. Moreover, TH started later (6 h) can worsen volume of brain lesion in females. These data indicate the need to develop specific therapeutic protocols for each sex and reinforce the importance of early onset of the hypothermic treatment.
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Affiliation(s)
- Rafael Bandeira Fabres
- Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil.
- Postgraduate Programme in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil.
- ICBS/UFRGS - Campus Centro, Rua Sarmento Leite, 500 - 2º Andar, 90050170, Porto Alegre, RS, Brazil.
| | - Ricardo Ribeiro Nunes
- Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
- Postgraduate Programme in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
| | - Marcel de Medeiros de Mattos
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, 90035-003, Porto Alegre, Brazil
| | - Mirella Kielek Galvan Andrade
- Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
| | - Ana Paula Rodrigues Martini
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, 90035-003, Porto Alegre, Brazil
- Postgraduate Programme in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
| | - Isadora D'Ávila Tassinari
- Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
- Postgraduate Programme in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
| | - Eduardo Farias Sanches
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, 90035-003, Porto Alegre, Brazil
- Postgraduate Programme in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
| | - Luciano Stürmer de Fraga
- Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
- Postgraduate Programme in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
| | - Carlos Alexandre Netto
- Postgraduate Programme in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, 90035-003, Porto Alegre, Brazil
- Postgraduate Programme in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Sarmento Leite, 500, 90050-170, Porto Alegre, Brazil
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19
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Komorowska D, Radzik T, Kalenik S, Rodacka A. Natural Radiosensitizers in Radiotherapy: Cancer Treatment by Combining Ionizing Radiation with Resveratrol. Int J Mol Sci 2022; 23:ijms231810627. [PMID: 36142554 PMCID: PMC9501384 DOI: 10.3390/ijms231810627] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/07/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022] Open
Abstract
Conventional cancer treatment is mainly based on the surgical removal of the tumor followed by radiotherapy and/or chemotherapy. When surgical removal is not possible, radiotherapy and, less often, chemotherapy is the only way to treat patients. However, despite significant progress in understanding the molecular mechanisms of carcinogenesis and developments in modern radiotherapy techniques, radiotherapy (alone or in combination) does not always guarantee treatment success. One of the main causes is the radioresistance of cancer cells. Increasing the radiosensitivity of cancer cells improves the processes leading to their elimination during radiotherapy and prolonging the survival of cancer patients. In order to enhance the effect of radiotherapy in the treatment of radioresistant neoplasms, radiosensitizers are used. In clinical practice, synthetic radiosensitizers are commonly applied, but scientists have recently focused on using natural products (phytocompounds) as adjuvants in radiotherapy. In this review article, we only discuss naturally occurring radiosensitizers currently in clinical trials (paclitaxel, curcumin, genistein, and papaverine) and those whose radiation sensitizing effects, such as resveratrol, have been repeatedly confirmed by many independent studies.
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Affiliation(s)
- Dominika Komorowska
- Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland
| | - Tomasz Radzik
- MARINEX International, 4 Placowa St., 93-446 Lodz, Poland
| | - Sebastian Kalenik
- Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland
| | - Aleksandra Rodacka
- Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland
- Correspondence: ; Fax: +48-426354473
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20
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Chumsuwan N, Khongkow P, Kaewsuwan S, Kanokwiroon K. Interruptin C, a Radioprotective Agent, Derived from Cyclosorus terminans Protect Normal Breast MCF-10A and Human Keratinocyte HaCaT Cells against Radiation-Induced Damage. Molecules 2022; 27:3298. [PMID: 35630775 PMCID: PMC9142933 DOI: 10.3390/molecules27103298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/12/2022] [Accepted: 05/14/2022] [Indexed: 01/27/2023] Open
Abstract
Radiotherapy is a common method to treat cancers, with the goal of maximizing the dose to tumors while minimizing the dose to normal tissues. Radioprotectors can reduce the toxicity to normal tissues during radiotherapy. Several plant-derived compounds can function as radioprotectors by scavenging free radicals. We investigated the radioprotective activity of interruptin C from the fern Cyclosorus terminans. The molecular mechanism of interruptin C's activity in X-ray-irradiated cells was evaluated. Superoxide dismutase activity was examined to investigate the antioxidant enzyme activity. Clonogenic cell survival was also investigated following radiation exposure. DNA damage and cell cycle progression were detected using micronuclei formation assays. DNA repair after irradiation was analyzed in a γH2AX assay. The levels of the proteins related to the radioprotective responses were analyzed by Western blotting. Interruptin C increased the antioxidant enzyme activity and significantly decreased the DNA damage by reducing the γH2AX foci and micronucleus formation in irradiated MCF-10A normal breast and HaCaT human keratinocyte cells. The apoptotic protein levels decreased, whereas the antiapoptotic protein levels increased. Interruptin C pretreatment increased the survival rate of irradiated MCF-10A and HaCaT cells. Moreover, the compound did not promote the survival of MDA-MB-231 and Hs578T breast cancer cells. Therefore, interruptin C may exert radioprotective activity without enhancing cancer cell proliferation.
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Affiliation(s)
- Nipha Chumsuwan
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (N.C.); (P.K.)
- Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
| | - Pasarat Khongkow
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (N.C.); (P.K.)
| | - Sireewan Kaewsuwan
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand;
- Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
| | - Kanyanatt Kanokwiroon
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (N.C.); (P.K.)
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21
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Fakhri S, Piri S, Moradi SZ, Khan H. Phytochemicals Targeting Oxidative Stress, Interconnected Neuroinflammatory, and Neuroapoptotic Pathways Following Radiation. Curr Neuropharmacol 2022; 20:836-856. [PMID: 34370636 PMCID: PMC9881105 DOI: 10.2174/1570159x19666210809103346] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/19/2021] [Accepted: 06/28/2021] [Indexed: 11/22/2022] Open
Abstract
The radiation for therapeutic purposes has shown positive effects in different contexts; however, it can increase the risk of many age-related and neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Parkinson's disease (PD). These different outcomes highlight a dose-response phenomenon called hormesis. Prevailing studies indicate that high doses of radiation could play several destructive roles in triggering oxidative stress, neuroapoptosis, and neuroinflammation in neurodegeneration. However, there is a lack of effective treatments in combating radiation-induced neurodegeneration, and the present drugs suffer from some drawbacks, including side effects and drug resistance. Among natural entities, polyphenols are suggested as multi-target agents affecting the dysregulated pathogenic mechanisms in neurodegenerative disease. This review discusses the destructive effects of radiation on the induction of neurodegenerative diseases by dysregulating oxidative stress, apoptosis, and inflammation. We also describe the promising effects of polyphenols and other candidate phytochemicals in preventing and treating radiation-induced neurodegenerative disorders, aiming to find novel/potential therapeutic compounds against such disorders.
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Affiliation(s)
- Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran;,Address correspondence to these author at the Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran; E-mail: Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan; E-mail:
| | - Sana Piri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran;,These authors have contributed equally to this work.
| | - Seyed Zachariah Moradi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran;,Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran;,These authors have contributed equally to this work.
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan,Address correspondence to these author at the Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran; E-mail: Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan; E-mail:
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22
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Pterostilbene Promotes Mean Lifespan in Both Male and Female Drosophila Melanogaster Modulating Different Proteins in the Two Sexes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:1744408. [PMID: 35222791 PMCID: PMC8865974 DOI: 10.1155/2022/1744408] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 11/17/2022]
Abstract
Aging is a multifactorial phenomenon characterized by degenerative processes closely connected to oxidative damage and chronic inflammation. Recently, many studies have shown that natural bioactive compounds are useful in delaying the aging process. In this work, we studied the effects of an in vivo supplementation of the stilbenoid pterostilbene on lifespan extension in Drosophila melanogaster. We found that the average lifespan of flies of both sexes was increased by pterostilbene supplementation with a higher effect in females. The expression of longevity related genes (Sir2, Foxo, and Notch) was increased in both sexes but with different patterns. Pterostilbene counteracted oxidative stress induced by ethanol and paraquat and up-regulated the antioxidant enzymes Ho e Trxr-1 in male but not in female flies. On the other hand, pterostilbene decreased the inflammatory mediators dome and egr only in female flies. Proteomic analysis revealed that pterostilbene modulates 113 proteins in male flies and only 9 in females. Only one of these proteins was modulated by pterostilbene in both sexes: vacuolar H[+] ATPase 68 kDa subunit 2 (Vha68-2) that was strongly down-regulated. These findings suggest a potential role of pterostilbene in increasing lifespan both in male and female flies by mechanisms that seem to be different in the two sexes, highlighting the need to conduct nutraceutical supplementation studies on males and females separately in order to give more reliable results.
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23
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Dobrzyńska MM, Gajowik A. Protection and Mitigation by Resveratrol of DNA Damage Induced in Irradiated Human Lymphocytes In Vitro. Radiat Res 2022; 197:149-156. [PMID: 34724059 DOI: 10.1667/rade-20-00037.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 08/30/2021] [Indexed: 11/03/2022]
Abstract
The aim of this study was to examine the protective and/or mitigative properties of resveratrol (RSV) administered before or after irradiation of human lymphocytes in vitro. The isolated lymphocytes were incubated for 1 h with resveratrol, at doses of 0.1 (lowest), 0.5 (medium) or 1 (highest) mM/ml: 1 h before; immediately before; immediately after irradiation; and 1 h after irradiation with 0.5, 1 and 2 Gy. The degree of DNA damage was evaluated by Comet Assay. Treatment of human lymphocytes with resveratrol 1 h before or immediately after radiation exposure showed protection from radiation-induced DNA damage. However, 1 Gy irradiation + 1 mM/ml RSV, and 2 Gy irradiation + 0.5 and 1 mM/ml RSV 1 h before irradiation did not provide the same protection. Significant dose-dependent reduction of the level of DNA damage was observed after application of RSV immediately postirradiation or 1 h postirradiation. The reduction in DNA damage was the highest at the 0.1 dose of resveratrol. Our results lead to the conclusion that resveratrol may act both as a radioprotector as well as a radiomitigator. Resveratrol at the lowest (0.5 mM/ml) dose was more effective when combined with 0.5 and 1 Gy doses of radiation.
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Affiliation(s)
- Małgorzata M Dobrzyńska
- National Institute of Public Health NIH - National Research Institute, Department of Radiation Hygiene and Radiobiology, 00-791 Warsaw, Poland
| | - Aneta Gajowik
- National Institute of Public Health NIH - National Research Institute, Department of Radiation Hygiene and Radiobiology, 00-791 Warsaw, Poland
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24
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Sadeghinezhad S, Khodamoradi E, Diojan L, Taeb S, Najafi M. Radioprotective Mechanisms of Arbutin: A Systematic Review. Curr Drug Res Rev 2022; 14:132-138. [PMID: 35319405 DOI: 10.2174/2589977514666220321114415] [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: 09/21/2021] [Revised: 12/15/2021] [Accepted: 01/06/2022] [Indexed: 06/14/2023]
Abstract
PURPOSE Efforts to produce radioprotective agents of high potential are appropriate strategies for overcoming possible IR toxicity in organisms. The present research aims to evaluate the signaling pathways and mechanisms through which arbutin exerts radioprotective effects on organisms. METHODS The databases of PubMed, Web of Sciences, Google Scholar, and Scopus were searched to find studies that reported radioprotective effects for arbutin. Besides, the data were searched within the time period from 2010 to 2020. RESULTS Five research articles met our criteria, which were included in the analysis based on their relevance to the topic. The present systematic review provides conclusions about various mechanisms and pathways through which arbutin induces radioprotection. CONCLUSIONS Based on the relevant studies, various mechanisms can be proposed for inducing radioprotective effects by arbutin, including inhibition of oxidative stress, apoptosis, and inflammation.
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Affiliation(s)
- Shima Sadeghinezhad
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ehsan Khodamoradi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Loghman Diojan
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shahram Taeb
- Department of Radiology, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Masoud Najafi
- Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
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25
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Shi PZ, Wang JW, Wang PC, Han B, Lu XH, Ren YX, Feng XM, Cheng XF, Zhang L. Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway. World J Stem Cells 2021; 13:1928-1946. [PMID: 35069991 PMCID: PMC8727228 DOI: 10.4252/wjsc.v13.i12.1928] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/12/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In degenerative intervertebral disc (IVD), an unfavorable IVD environment leads to increased senescence of nucleus pulposus (NP)-derived mesenchymal stem cells (NPMSCs) and the inability to complete the differentiation from NPMSCs to NP cells, leading to further aggravation of IVD degeneration (IDD). Urolithin A (UA) has been proven to have obvious effects in delaying cell senescence and resisting oxidative stress.
AIM To explore whether UA can alleviate NPMSCs senescence and to elucidate the underlying mechanism.
METHODS In vitro, we harvested NPMSCs from rat tails, and divided NPMSCs into four groups: the control group, H2O2 group, H2O2 + UA group, and H2O2 + UA + SR-18292 group. Senescence-associated β-Galactosidase (SA-β-Gal) activity, cell cycle, cell proliferation ability, and the expression of senescence-related and silent information regulator of transcription 1/PPAR gamma coactivator-1α (SIRT1/ PGC-1α) pathway-related proteins and mRNA were used to evaluate the protective effects of UA. In vivo, an animal model of IDD was constructed, and X-rays, magnetic resonance imaging, and histological analysis were used to assess whether UA could alleviate IDD in vivo.
RESULTS We found that H2O2 can cause NPMSCs senescence changes, such as cell cycle arrest, reduced cell proliferation ability, increased SA-β-Gal activity, and increased expression of senescence-related proteins and mRNA. After UA pretreatment, the abovementioned senescence indicators were significantly alleviated. To further demonstrate the mechanism of UA, we evaluated the mitochondrial membrane potential and the SIRT1/PGC-1α pathway that regulates mitochondrial function. UA protected mitochondrial function and delayed NPMSCs senescence by activating the SIRT1/PGC-1α pathway. In vivo, we found that UA treatment alleviated an animal model of IDD by assessing the disc height index, Pfirrmann grade and the histological score.
CONCLUSION In summary, UA could activate the SIRT1/PGC-1α signaling pathway to protect mitochondrial function and alleviate cell senescence and IDD in vivo and vitro.
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Affiliation(s)
- Peng-Zhi Shi
- Department of Orthopedic, Dalian Medical University, Dalian 116000, Liaoning Province, China
| | - Jun-Wu Wang
- Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
| | - Ping-Chuan Wang
- Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
| | - Bo Han
- Department of Orthopedic, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Xu-Hua Lu
- Department of Orthopedics, Changzheng Hospital of The Second Military Medical University, Shanghai 200003, China
| | - Yong-Xin Ren
- Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xin-Min Feng
- Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
| | - Xiao-Fei Cheng
- Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedics Implants, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, China
| | - Liang Zhang
- Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
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Lv S, Li X, Zhao S, Liu H, Wang H. The Role of the Signaling Pathways Involved in the Protective Effect of Exogenous Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury. Front Cell Dev Biol 2021; 9:723569. [PMID: 34527675 PMCID: PMC8435706 DOI: 10.3389/fcell.2021.723569] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/11/2021] [Indexed: 01/19/2023] Open
Abstract
Ischemia/reperfusion (I/R) injury refers to the functional and structural changes in the process of blood flow recovery after ischemia. In addition to ischemia, the blood flow recovery can also lead to very harmful damage, such as the obvious cell swelling and the irreversible cell necrosis. I/R injury is related with many diseases, including myocardial I/R injury. Myocardial I/R injury refers to the aggravation of ischemic myocardial tissue injury due to sudden disorder of blood circulation. Although there are many studies on myocardial I/R injury, the exact mechanism is not fully understood. Hydrogen sulfide (H2S), like carbon monoxide and nitric oxide, is an important gas signal molecule. It plays an important role in many physiological and pathological processes. Recent studies indicate that H2S can improve myocardial I/R injury, however, its mechanism is not fully understood, especially the involved signal pathways. In this review, we summarize the related researches about the role of the signaling pathways involved in the protective effects of exogenous H2S on myocardial I/R injury, so as to provide theoretical reference for the future in-depth researches.
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Affiliation(s)
- Shuangyu Lv
- Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Xiaotian Li
- Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Shizhen Zhao
- Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Huiyang Liu
- Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Honggang Wang
- Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China
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27
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Qin H, Zhang H, Zhang S, Zhu S, Wang H. Protective Effect of Sirt1 against Radiation-Induced Damage. Radiat Res 2021; 196:647-657. [PMID: 34459925 DOI: 10.1667/rade-20-00139.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 08/11/2021] [Indexed: 11/03/2022]
Abstract
Radiotherapy is an important method for the treatment of malignant tumors. It can directly or indirectly lead to the formation of free radicals and DNA damage, resulting in a series of biological effects, including tumor cell death and normal tissue damage. These radiation effects are typically accompanied by the abnormal expression of sirtuin 1 (Sirt1), which deacetylates histones and non-histones. These Sirt1 substrates, including transcription factors and some catalytic enzymes, play a crucial role in anti-oxidative stress, DNA damage repair, autophagy regulation, anti-senescence, and apoptosis, which are closely related to triggering cell defense and survival in radiation-induced damage. In this article, we review the mechanisms underlying cellular responses to ionizing radiation and the role of Sirt1 in the process, with the aim of providing a theoretical basis for protection against radiation by Sirt1 as well as novel targets for developing radioprotective agents.
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Affiliation(s)
- Haoren Qin
- Tianjin University of Traditional Chinese Medicine, Tianjin, P.R. China
| | - Heng Zhang
- Department of Oncology, Institute of Integrative Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, P.R. China
| | - Shiwu Zhang
- Department of Pathology, Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, P.R. China
| | - Siwei Zhu
- Department of Oncology, Institute of Integrative Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, P.R. China
| | - Hui Wang
- Department of Oncology, Institute of Integrative Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, P.R. China
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28
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Lee MTW, Mahy W, Rackham MD. The medicinal chemistry of mitochondrial dysfunction: a critical overview of efforts to modulate mitochondrial health. RSC Med Chem 2021; 12:1281-1311. [PMID: 34458736 PMCID: PMC8372206 DOI: 10.1039/d1md00113b] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/17/2021] [Indexed: 12/16/2022] Open
Abstract
Mitochondria are subcellular organelles that perform a variety of critical biological functions, including ATP production and acting as hubs of immune and apoptotic signalling. Mitochondrial dysfunction has been extensively linked to the pathology of multiple neurodegenerative disorders, resulting in significant investment from the drug discovery community. Despite extensive efforts, there remains no disease modifying therapies for neurodegenerative disorders. This manuscript aims to review the compounds historically used to modulate the mitochondrial network through the lens of modern medicinal chemistry, and to offer a perspective on the evidence that relevant exposure was achieved in a representative model and that exposure was likely to result in target binding and engagement of pharmacology. We hope this manuscript will aid the community in identifying those targets and mechanisms which have been convincingly (in)validated with high quality chemical matter, and those for which an opportunity exists to explore in greater depth.
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Affiliation(s)
| | - William Mahy
- MSD The Francis Crick Institute 1 Midland Road London NW1 1AT UK
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29
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Comparison of malondialdehyde levels and superoxide dismutase activity in resveratrol and resveratrol/donepezil combination treatment groups in Alzheimer's disease induced rat model. 3 Biotech 2021; 11:329. [PMID: 34189010 PMCID: PMC8200337 DOI: 10.1007/s13205-021-02879-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 06/02/2021] [Indexed: 01/18/2023] Open
Abstract
The aim of this study was to determine the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in colchicine induced Alzheimer’s disease (AD), resveratrol (RS) treated and RS + donepezil (DPZ) treated rat models. The objective was to compare the MDA level and SOD activity among these rat models. The present study included 3 months old male albino Wistar rats, which were in-house bred and weighting about 220–250 g. The rats were divided into nine subgroups which included control, sham, AD induced, RS treated and DPZ treated groups in different doses and combinations. The lipid peroxidation product for MDA in the brain homogenate was measured by estimating the levels of thiobarbituric acid reactive substance. Estimation of SOD was done by the method of autoxidation of pyrogallol by Marklund and Marklund. There was a marked increase in the MDA levels in AD induced group in comparison to the control group (p < 0.05). The SOD activity was higher in the RS 10 and RS 20 treated groups in contrast to the AD group (p < 0.05). In DPZ + RS group, there was a substantial increase in the SOD activity (p < 0.05). It is also observed that the RS 20 treatment group showed higher SOD activity than the RS 10 group (p < 0.05). This study showed that, AD induced group had elevated levels of MDA, which indicates the poor oxidative stress–defence mechanism. The RS 10 and RS 20 groups showed higher SOD activity in comparison to the AD group, which indicated the improved oxidative stress–defence mechanism. The RS + DPZ group showed higher SOD activity, indicating a synergistic effect of DPZ and RS.
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30
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Ahmadi A, Hayes AW, Karimi G. Resveratrol and endoplasmic reticulum stress: A review of the potential protective mechanisms of the polyphenol. Phytother Res 2021; 35:5564-5583. [PMID: 34114705 DOI: 10.1002/ptr.7192] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/27/2021] [Accepted: 05/27/2021] [Indexed: 12/13/2022]
Abstract
The endoplasmic reticulum (ER) is an organelle that performs a set of essential functions in cellular biology. These include synthesis of lipids, homeostasis of calcium, and controlling the folding of proteins. Inflammation and oxidative stress are two important reasons behind the accumulation of misfolded or unfolded proteins in the ER. In such circumstances, a series of measures are undertaken in the cell which are collectively called unfolded protein response (UPR). The aim of UPR is to reduce the burden of protein aggregates and promote survival. However, extended and unrestricted ER stress (ERS) can induce further inflammation and apoptosis. ERS and the UPR are involved in different diseases such as neurodegenerative and cardiovascular diseases. Resveratrol (RSV), a natural polyphenol, has well-documented evidence supporting its numerous biological properties including antioxidant, antiinflammatory, antiobesity, antidiabetic, and antiischemic activities. The compound is also known for its potential beneficial effects on cognitive function and liver, kidney, and lung health. In this review, the role of ERS in several pathological conditions and the potential protective effects of RSV are discussed. However, the scarcity of clinical data means that more research needs to be conducted to gain a lucid understanding of RSV's effects on endoplasmic reticulum stress (ERS) in humans.
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Affiliation(s)
- Ali Ahmadi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A Wallace Hayes
- University of South Florida, Tampa, FL USA and Michigan State University, East Lansing, Michigan, USA
| | - Gholamreza Karimi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.,Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
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Calvello R, Cianciulli A, Porro C, Moda P, De Nuccio F, Nicolardi G, Giannotti L, Panaro MA, Lofrumento DD. Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model. Nutrients 2021; 13:nu13051418. [PMID: 33922475 PMCID: PMC8147048 DOI: 10.3390/nu13051418] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 04/17/2021] [Accepted: 04/21/2021] [Indexed: 12/11/2022] Open
Abstract
Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds.
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Affiliation(s)
- Rosa Calvello
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, I-70125 Bari, Italy; (R.C.); (A.C.)
| | - Antonia Cianciulli
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, I-70125 Bari, Italy; (R.C.); (A.C.)
| | - Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, I-71100 Foggia, Italy;
| | - Piergianni Moda
- Nuclear Medicine Department, SS. Annunziata Hospital, I-74100 Taranto, Italy;
| | - Francesco De Nuccio
- Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, I-73100 Lecce, Italy; (F.D.N.); (G.N.); (L.G.); (D.D.L.)
| | - Giuseppe Nicolardi
- Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, I-73100 Lecce, Italy; (F.D.N.); (G.N.); (L.G.); (D.D.L.)
| | - Laura Giannotti
- Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, I-73100 Lecce, Italy; (F.D.N.); (G.N.); (L.G.); (D.D.L.)
| | - Maria Antonietta Panaro
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, I-70125 Bari, Italy; (R.C.); (A.C.)
- Correspondence:
| | - Dario Domenico Lofrumento
- Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, I-73100 Lecce, Italy; (F.D.N.); (G.N.); (L.G.); (D.D.L.)
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32
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Agbele AT, Fasoro OJ, Fabamise OM, Oluyide OO, Idolor OR, Bamise EA. Protection Against Ionizing Radiation-Induced Normal Tissue Damage by Resveratrol: A Systematic Review. Eurasian J Med 2020; 52:298-303. [PMID: 33209085 DOI: 10.5152/eurasianjmed.2020.20143] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The use of some agents as radioprotectors has been evaluated for protection against normal tissue toxicity following exposure to ionizing radiation. Resveratrol, a natural flavonoid, with antioxidant and anti-inflammatory properties has attracted research interests for its radioprotective potential. This study systematically evaluates existing studies to examine the radioprotective effectiveness of resveratrol. A literature search of the electronic databases, including PubMed, Scopus, and Embase was conducted to retrieve articles investigating the protective effect of resveratrol against ionizing radiation-induced damage to normal tissues. The search timeframe ranged from the inception of each database to January 2020. From an initial search of 231 articles, and after the removal of duplicates as well as applying the predetermined inclusion and exclusion criteria, 33 articles were finally included for this systematic review. Results showed promising protective effect of resveratrol against ionizing radiation-induced damage to normal tissues. Furthermore, no adverse effect was observed after administering resveratrol. Resveratrol showed the potential to protect against ionizing radiation-induced damage to normal tissue cells via notable mechanisms, including anti-apoptotic and anti-inflammatory effects. However, further studies on the efficacy of clinical translation of resveratrol would open up more insights, while other gray areas such as the optimal radioprotective dosage of resveratrol requires further investigation. Overall, resveratrol is a potential double-edged sword in cancer therapy while protecting healthy tissues.
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Affiliation(s)
- Alaba Tolulope Agbele
- Department of Medical Physics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Department of Basic Medical Sciences, College of Health Sciences and Technology, Ijero-Ekiti, Ekiti State, Nigeria
| | - Olatunji Jimoh Fasoro
- Department of Pharmacy, College of Health Sciences and Technology, Ijero-Ekiti, Ekiti State, Nigeria
| | - Olufemi Moses Fabamise
- Department of Basic Medical Sciences, College of Health Sciences and Technology, Ijero-Ekiti, Ekiti State, Nigeria
| | - Oluwabusayo Odunola Oluyide
- Department of Basic Medical Sciences, College of Health Sciences and Technology, Ijero-Ekiti, Ekiti State, Nigeria
| | | | - Esther Abosede Bamise
- Department of Basic Medical Sciences, College of Health Sciences and Technology, Ijero-Ekiti, Ekiti State, Nigeria
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Khalil A, Al-Massarani G, Aljapawe A, Ekhtiar A, Bakir MA. Resveratrol Modulates the Inflammatory Profile of Immune Responses and Circulating Endothelial Cells' (CECs') Population During Acute Whole Body Gamma Irradiation. Front Pharmacol 2020; 11:528400. [PMID: 33013379 PMCID: PMC7500447 DOI: 10.3389/fphar.2020.528400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 08/20/2020] [Indexed: 11/15/2022] Open
Abstract
Wistar rats were whole body irradiated with a single dose of 2 Gy post administration with 10 or 100 mg/kg of resveratrol (RSV) intraperitoneally for 30 days. Rats’ livers were dissected and processed to analyze immune response profiles of Th1, Th2, Th9, Th17, and Th22 by flow cytometry. In addition, peripheral blood samples were collected and circulating endothelial cells (CECs) were counted as an indicator for endothelial damage. Results demonstrated that resveratrol at 100 mg/kg enhanced liver immunological response influenced by irradiation by inducing Th2 immune response that was revealed by an increase in IL-10 secretion to more than 5,000 pmol/ml post irradiation. Results also indicated that RSV, at a dose of 100 mg/kg, decreased levels of the main pro-inflammatory cytokines such as INF-γ, IL-22, IL-17A, and GM-CSF post irradiation. In addition, the same RSV was bound to upregulate the expression of IL-10 mRNA in isolated Kupffer cells (KCs) and their secretion of IL-10 post irradiation. The result demonstrated that KCs were the central source of this anti-inflammatory response mediated mainly by IL10. These results, proposed for the first time, clearly states that RSV promotes IL-10 mediated immune resolution by Kupffer cells and not by hepatocytes. This implies that KCs have a crucial role in radiotherapy. Additionally, this study showed that RSV had an anti-apoptotic effect through re-increasing the number of CECs, which is implicated in irradiation damage. Result of the current work discloses novel findings about the potential of RSV as a radio-protector agent of a natural origin and suggests novel roles of KCs as a pharmacological target during radiation exposure.
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Affiliation(s)
- Ayman Khalil
- Human Nutrition Laboratory, Department of Radiation Medicine, Atomic Energy Commission of Syria (AECS), Damascus, Syria
| | - Ghassan Al-Massarani
- Biomarkers Laboratory, Radiation Medicine Department, Atomic Energy Commission of Syria (AECS), Damascus, Syria
| | - Abdulmunim Aljapawe
- Flow Cytometry Laboratory, Biotechnology and Molecular Biology Department, Atomic Energy Commission of Syria (AECS), Damascus, Syria
| | - Adnan Ekhtiar
- Flow Cytometry Laboratory, Biotechnology and Molecular Biology Department, Atomic Energy Commission of Syria (AECS), Damascus, Syria
| | - M Adel Bakir
- Radiation Medicine Department, Atomic Commission of Syria (AECS), Damascus, Syria
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Broderick TL, Rasool S, Li R, Zhang Y, Anderson M, Al-Nakkash L, Plochocki JH, Geetha T, Babu JR. Neuroprotective Effects of Chronic Resveratrol Treatment and Exercise Training in the 3xTg-AD Mouse Model of Alzheimer's Disease. Int J Mol Sci 2020; 21:ijms21197337. [PMID: 33020412 PMCID: PMC7582460 DOI: 10.3390/ijms21197337] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 09/22/2020] [Accepted: 09/24/2020] [Indexed: 12/11/2022] Open
Abstract
To date, there is no cure or effective treatment for Alzheimer’s disease (AD), a chronic neurodegenerative condition that affects memory, language, and behavior. AD is characterized by neuroinflammation, accumulation of brain amyloid-beta (Aβ) oligomers and neurofibrillary tangles, increased neuronal apoptosis, and loss of synaptic function. Promoting regular exercise and a diet containing polyphenols are effective non-pharmacological approaches that prevent the progression of neurodegenerative diseases. In this study, we measured various conformational toxic species of Aβ and markers of inflammation, apoptosis, endolysosomal degradation, and neuroprotection after 5 months of exercise training (ET), resveratrol (Resv) treatment, or combination treatment in the 3xTg-AD mouse model of AD. Our main results indicate that Resv decreased neuroinflammation and accumulation of Aβ oligomers, increased levels of neurotrophins, synaptic markers, silent information regulator, and decreased markers of apoptosis, autophagy, endolysosomal degradation and ubiquitination in the brains of 3xTg-AD mice. ET improved some markers related to neuroprotection, but when combined with Resv treatment, the benefits achieved were as effective as Resv treatment alone. Our results show that the neuroprotective effects of Resv, ET or Resv and ET are associated with reduced toxicity of Aβ oligomers, suppression of neuronal autophagy, decreased apoptosis, and upregulation of key growth-related proteins.
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Affiliation(s)
- Tom L. Broderick
- Department of Physiology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA;
- Laboratory of Diabetes and Exercise Metabolism, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA;
- Correspondence: (T.L.B.); (J.R.B.)
| | - Suhail Rasool
- Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA; (S.R.); (R.L.); (Y.Z.); (T.G.)
| | - Rongzi Li
- Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA; (S.R.); (R.L.); (Y.Z.); (T.G.)
| | - Yuxian Zhang
- Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA; (S.R.); (R.L.); (Y.Z.); (T.G.)
| | - Miranda Anderson
- Laboratory of Diabetes and Exercise Metabolism, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA;
| | - Layla Al-Nakkash
- Department of Physiology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA;
| | - Jeffrey H. Plochocki
- Department of Medical Education, University of Central Florida, College of Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827, USA;
| | - Thangiah Geetha
- Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA; (S.R.); (R.L.); (Y.Z.); (T.G.)
| | - Jeganathan Ramesh Babu
- Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA; (S.R.); (R.L.); (Y.Z.); (T.G.)
- Correspondence: (T.L.B.); (J.R.B.)
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Yuce P, Hosgor H, Rencber SF, Yazir Y. Effects of Intra-Articular Resveratrol Injections on Cartilage Destruction and Synovial Inflammation in Experimental Temporomandibular Joint Osteoarthritis. J Oral Maxillofac Surg 2020; 79:344.e1-344.e12. [PMID: 33039343 DOI: 10.1016/j.joms.2020.09.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 09/10/2020] [Accepted: 09/10/2020] [Indexed: 01/11/2023]
Abstract
PURPOSE The aim of this study was to investigate the effects of intra-articular resveratrol injections on cartilage destruction and synovial inflammation in an experimental temporomandibular joint osteoarthritis (TMJ-OA) model. MATERIALS AND METHODS Freund's complete adjuvant injection method was used to construct the TMJ-OA model. Twenty-eight male Wistar rats were randomly placed into 4 groups: control (n = 4), TMJ arthritis (n = 8), low-dose intra-articular resveratrol (RES[L]; n = 8), and high-dose intra-articular resveratrol (RES[H]; n = 8). Intra-articular injections of resveratrol were performed 3 times at 1-week intervals, 1 week after the administration of a single dose of Freund's complete adjuvant to the TMJ. The effects of resveratrol on cartilage destruction and synovial inflammation were examined histopathologically. The histomorphometric examination revealed condylar cartilage and articular disc thickness. An apoptotic chondrocyte count was performed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and matrix metalloproteinase 13 expression was evaluated through an immunohistochemical examination. RESULTS The thickness of the condylar cartilage in the RES(L) and RES(H) groups was statistically significantly greater than that in the control and TMJ arthritis groups (P < .05). The inflammation-induced articular disc thickening was significantly lower in the RES(L) and RES(H) groups (P < .05). The chondrocyte apoptosis in the RES(L) and RES(H) groups was significantly lower than that in the TMJ arthritis group (P < .05). The matrix metalloproteinase 13 expression in the RES(L) and RES(H) groups was obviously less than that in the TMJ arthritis group (P < .05). CONCLUSIONS The intra-articular resveratrol treatment exerted a curative effect by preventing the inflammation and cartilage destruction associated with TMJ-OA.
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Affiliation(s)
- Pinar Yuce
- Private Practitioner, Private Dental Clinic, Kocaeli, Turkey
| | - Hatice Hosgor
- Assistant Professor, Kocaeli University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Kocaeli, Turkey.
| | - Selenay Furat Rencber
- Research Assistant, Kocaeli University, Faculty of Medicine, Department of Histology Embryology, Kocaeli, Turkey
| | - Yusufhan Yazir
- Professor, Kocaeli University, Faculty of Medicine, Department of Histology Embryology, Kocaeli, Turkey
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Koca G, Singar E, Akbulut A, Yazihan N, Yumuşak N, Demir A, Korkmaz M. The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage. Curr Eye Res 2020; 46:398-407. [PMID: 32730712 DOI: 10.1080/02713683.2020.1803920] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
PURPOSE We have evaluated the potential radioprotective, antioxidant and anti-apoptotic effects of resveratrol (RSV) against high-dose radioactive iodine (RAI) therapy associated damage of the lacrimal glands by biochemical, histopathological and immunohistochemical methods. MATERIALS AND METHODS Thirty Wistar-albino rats were randomly divided into three groups; the control group received no treatment or medication, the RAI group received RAI but no medication and the RSV group received oral RAI and intraperitoneal RSV. RSV was started at day one, before RAI administration, and continued for 8 days. Bilateral intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were evaluated in all rats for histopathological, immunohistochemical, tissue cytokine and oxidant and antioxidant level assessment. RESULTS RSV group restored inflammation, fibrosis, vacuolization, change in nucleus characteristics, lipofuscin-like accumulation and cellular morphologic patterns were statistically significant in all lacrimal gland types, compared to the RAI group (p < .05 for all variables). Similarly, elevated Caspase-3 and TUNEL levels in the RAI group were significantly alleviated in the RSV group in all lacrimal gland types (p < .05 for all variables). RAI administration significantly elevated TNF-α, IL-6, NF-кb levels, and decreased IL-10 levels (p < .05 for all parameters) whereas TOS levels significantly increased and TAS levels were significantly decreased. However, RSV significantly diminished TNF-α, IL-6, IL-4, and NF-кb levels. Furthermore, RSV significantly decreased TOS and increased TAS levels (p < .05 for all variables). CONCLUSIONS We conclude that with its anti-cancer effect as well as its antioxidant effect RSV has protected the histopathological pattern of the lacrimal glands from the damage, decreased inflammation in histopathologic assessments, and decreased tissue cytokine levels, apoptosis and DNA fragmentation on the lacrimal glands after RAI.
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Affiliation(s)
- Gökhan Koca
- Department of Nuclear Medicine, Ankara Training and Application Hospital, University of Health Sciences , Ankara, Turkey
| | - Evin Singar
- Department of Ophthalmology, Ankara Training and Application Hospital, University of Health Sciences , Ankara, Turkey
| | - Aylin Akbulut
- Department of Nuclear Medicine, Ankara Training and Application Hospital, University of Health Sciences , Ankara, Turkey
| | - Nuray Yazihan
- Department of Pathophysiology, Ankara University School of Medicine , Ankara, Turkey
| | - Nihat Yumuşak
- Department of Pathology, Harran University Faculty of Veterinary Medicine , Sanliurfa, Turkey
| | - Ayten Demir
- Faculty of Health Sciences, Nursing Department, Ankara University , Ankara, Turkey
| | - Meliha Korkmaz
- Department of Nuclear Medicine, Ankara Training and Application Hospital, University of Health Sciences , Ankara, Turkey
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Soo SK, Rudich PD, Traa A, Harris-Gauthier N, Shields HJ, Van Raamsdonk JM. Compounds that extend longevity are protective in neurodegenerative diseases and provide a novel treatment strategy for these devastating disorders. Mech Ageing Dev 2020; 190:111297. [PMID: 32610099 PMCID: PMC7484136 DOI: 10.1016/j.mad.2020.111297] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 06/24/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022]
Abstract
While aging is the greatest risk factor for the development of neurodegenerative disease, the role of aging in these diseases is poorly understood. In the inherited forms of these diseases, the disease-causing mutation is present from birth but symptoms appear decades later. This indicates that these mutations are well tolerated in younger individuals but not in older adults. Based on this observation, we hypothesized that changes taking place during normal aging make the cells in the brain (and elsewhere) susceptible to the disease-causing mutations. If so, then delaying some of these age-related changes may be beneficial in the treatment of neurodegenerative disease. In this review, we examine the effects of five compounds that have been shown to extend longevity (metformin, rapamycin, resveratrol, N-acetyl-l-cysteine, curcumin) in four of the most common neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis). While not all investigations observe a beneficial effect of these compounds, there are multiple studies that show a protective effect of each of these lifespan-extending compounds in animal models of neurodegenerative disease. Combined with genetic studies, this suggests the possibility that targeting the aging process may be an effective strategy to treat neurodegenerative disease.
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Affiliation(s)
- Sonja K Soo
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H4A 3J1, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada
| | - Paige D Rudich
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H4A 3J1, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada
| | - Annika Traa
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H4A 3J1, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada
| | - Namasthée Harris-Gauthier
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H4A 3J1, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada
| | - Hazel J Shields
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H4A 3J1, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada
| | - Jeremy M Van Raamsdonk
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H4A 3J1, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, H4A 3J1, Canada; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
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Qian L, Cen J. Hematopoietic Stem Cells and Mesenchymal Stromal Cells in Acute Radiation Syndrome. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:8340756. [PMID: 32855768 PMCID: PMC7443042 DOI: 10.1155/2020/8340756] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 07/02/2020] [Accepted: 07/24/2020] [Indexed: 02/08/2023]
Abstract
With the extensive utilization of radioactive materials for medical, industrial, agricultural, military, and research purposes, medical researchers are trying to identify new methods to treat acute radiation syndrome (ARS). Radiation may cause injury to different tissues and organs, but no single drug has been proven to be effective in all circumstances. Radioprotective agents are always effective if given before irradiation, but many nuclear accidents are unpredictable. Medical countermeasures that can be beneficial to different organ and tissue injuries caused by radiation are urgently needed. Cellular therapy, especially stem cell therapy, has been a promising approach in ARS. Hematopoietic stem cells (HSCs) and mesenchymal stromal cells (MSCs) are the two main kinds of stem cells which show good efficacy in ARS and have attracted great attention from researchers. There are also some limitations that need to be investigated in future studies. In recent years, there are also some novel methods of stem cells that could possibly be applied on ARS, like "drug" stem cell banks obtained from clinical grade human induced pluripotent stem cells (hiPSCs), MSC-derived products, and infusion of HSCs without preconditioning treatment, which make us confident in the future treatment of ARS. This review focuses on major scientific and clinical advances of hematopoietic stem cells and mesenchymal stromal cells on ARS.
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Affiliation(s)
- Liren Qian
- Department of Hematology, The Sixth Medical Center, Chinese PLA General Hospital, Fucheng Road #6, Beijing 100048, China
| | - Jian Cen
- Department of Hematology, The Sixth Medical Center, Chinese PLA General Hospital, Fucheng Road #6, Beijing 100048, China
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Shrishrimal S, Chatterjee A, Kosmacek EA, Davis PJ, McDonald JT, Oberley-Deegan RE. Manganese porphyrin, MnTE-2-PyP, treatment protects the prostate from radiation-induced fibrosis (RIF) by activating the NRF2 signaling pathway and enhancing SOD2 and sirtuin activity. Free Radic Biol Med 2020; 152:255-270. [PMID: 32222469 PMCID: PMC7276298 DOI: 10.1016/j.freeradbiomed.2020.03.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/20/2020] [Accepted: 03/21/2020] [Indexed: 12/13/2022]
Abstract
Radiation therapy is a frequently used treatment for prostate cancer patients. Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or BMX-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of radiation-induced fibrosis (RIF). However, understanding the molecular pathway changes associated with these compounds remains limited for radioprotection. Recent RNA-sequencing data from our laboratory revealed that MnTE-2-PyP treatment activated the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Therefore, we hypothesize that MnTE-2-PyP protects the prostate from RIF by activating the NRF2 signaling pathway. We identified that MnTE-2-PyP is a post-translational activator of NRF2 signaling in prostate fibroblast cells, which plays a major role in fibroblast activation and myofibroblast differentiation. The mechanism of NRF2 activation involves an increase in hydrogen peroxide and a corresponding decrease in kelch-like ECH-associated protein 1 (KEAP1) levels. Activation of NRF2 signaling leads to an increase in expression of NAD(P)H dehydrogenase [quinone] 1 (NQO1), nicotinamide adenine dinucleotide (NAD+) levels, sirtuin activity (nuclear and mitochondrial), and superoxide dismutase 2 (SOD2) expression/activity. Increase in mitochondrial sirtuin activity correlates with a decrease in SOD2 (K122) acetylation. This decrease in SOD2 K122 acetylation correlates with an increase in SOD2 activity and mitochondrial superoxide scavenging capacity. Further, in human primary prostate fibroblast cells, the NRF2 pathway plays a major role in the fibroblast to myofibroblast transformation, which is responsible for the fibrotic phenotype. In the context of radiation protection, MnTE-2-PyP fails to prevent fibroblast to myofibroblast transformation in the absence of NRF2 signaling. Collectively, our results indicate that the activation of the NRF2 signaling pathway by MnTE-2-PyP is at least a partial mechanism of radioprotection in prostate fibroblast cells.
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Affiliation(s)
- Shashank Shrishrimal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Arpita Chatterjee
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Elizabeth A Kosmacek
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | | | - J Tyson McDonald
- Department of Physics, Hampton University, Hampton, VA, 23668, USA
| | - Rebecca E Oberley-Deegan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
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The Neuroprotective Effects of Astragaloside IV against H 2O 2-Induced Damage in SH-SY5Y Cells are Associated with Synaptic Plasticity. J CHEM-NY 2020. [DOI: 10.1155/2020/5343619] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
The aim of this study was to investigate whether the neuroprotective effects of astragaloside IV (AS-IV) against hydrogen peroxide (H2O2)-induced damage on human neuroblastoma cell line (SH-SY5Y) are associated with synaptic plasticity. The concentration screening of AS-IV and H2O2 on SH-SY5Y cells and the protective effects of AS-IV on SH-SY5Y cells under H2O2 stress were all determined by MTT assay. The expression of postsynaptic density 95 (PSD-95) and growth-associated protein 43 (GAP-43) were measured by western blot (WB) and inmunofluorescence staining assay under the same treatment conditions. According to the MTT results, the concentration of H2O2 at 50 μmol/L for 3 h was used for the cell damage model, and various concentrations of AS-IV (0.1, 0.2, 0.3, and 0.4 μmol/L) were used to affect SH-SY5Y cells. The MTT results showed that pretreatment of SH-SY5Y cells with AS-IV (0.1, 0.2, 0.3, and 0.4 μmol/L) attenuated the damage induced by H2O2 (50 μmol/L, 51.62% cell viability) and increased cell viability to 64.19, 63.48, 65.86, and 65.81%, respectively. Western blot analysis and immunofluorescence staining showed that the protective effects of AS-IV against SH-SY5Y cell damage caused by H2O2 resulted in reduced expression of PSD-95 and increased expression of GAP-43 in comparison with the H2O2 treatment group. The conclusion shows that AS-IV protected SH-SY5Y cells and enhanced their viability under H2O2 stress. AS-IV may facilitate presynaptic and postsynaptic plasticity to exert protective effects against oxidative damage of SH-SY5Y cells.
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Yue Y, Huo F, Pei X, Wang Y, Yin C. Fluorescent Imaging of Resveratrol Induced Subcellular Cysteine Up-Regulation. Anal Chem 2020; 92:6598-6603. [DOI: 10.1021/acs.analchem.0c00363] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Yongkang Yue
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
| | - Fangjun Huo
- Research Institute of Applied Chemistry, Shanxi University, Taiyuan 030006, China
| | - Xueying Pei
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
| | - Yuting Wang
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
| | - Caixia Yin
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
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Meng X, Zhou J, Zhao CN, Gan RY, Li HB. Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review. Foods 2020; 9:340. [PMID: 32183376 PMCID: PMC7143620 DOI: 10.3390/foods9030340] [Citation(s) in RCA: 189] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 03/10/2020] [Accepted: 03/12/2020] [Indexed: 12/16/2022] Open
Abstract
Resveratrol is a bioactive compound in many foods. Since its anticancer activity was reported in 1997, its health benefits have been intensively investigated. Resveratrol has antioxidant, anti-inflammatory, immunomodulatory, glucose and lipid regulatory, neuroprotective, and cardiovascular protective effects, therefore, can protect against diverse chronic diseases, such as cardiovascular diseases (CVDs), cancer, liver diseases, obesity, diabetes, Alzheimer's disease, and Parkinson's disease. This review summarizes the main findings of resveratrol-related health benefits in recent epidemiological surveys, experimental studies, and clinical trials, highlighting its related molecular mechanisms. Resveratrol, therefore, has been regarded as a potent candidate for the development of nutraceuticals and pharmaceuticals to prevent and treat certain chronic diseases.
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Affiliation(s)
- Xiao Meng
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.M.); (H.-B.L.)
| | - Jing Zhou
- School of Public Health, Hainan Medical University, Haikou 571199, China;
| | - Cai-Ning Zhao
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;
| | - Ren-You Gan
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (X.M.); (H.-B.L.)
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Liang D, Zhuo Y, Guo Z, He L, Wang X, He Y, Li L, Dai H. SIRT1/PGC-1 pathway activation triggers autophagy/mitophagy and attenuates oxidative damage in intestinal epithelial cells. Biochimie 2019; 170:10-20. [PMID: 31830513 DOI: 10.1016/j.biochi.2019.12.001] [Citation(s) in RCA: 112] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 12/06/2019] [Indexed: 02/07/2023]
Abstract
Oxidative stress leads to intestinal epithelial cells damage, which induces tight junction injury and systemic endogenous stress syndrome. The evidence suggests that SIRT1/PGC-1α pathway is closely associated with oxidative damage. However, the mechanism in protecting intestinal epithelial cells against oxidative stress dependant on autopahgy/mitophagy remains to be elucidated. In the current study, we investigated the functional role of SIRT1/PGC-1α pathway on regulation of autopahgy/mitophagy and tight junction protein expression underlying the oxidative dysfunction in porcine intestinal epithelial cells (IPEC-1). Results demonstrated that H2O2 exposure caused high accumulation of ROS, with a decrease of mitochondrial membrane potential and an inhibition of the tight junction molecules in IPEC-1 cells. Also, COX IV mRNA expression and SIRT1/PGC-1α pathway were suppressed. Autophagy and PINK1/Parkin dependant-mitophagy were activated following H2O2 treatment. Further research indicated that activation of SIRT1/PGC-1α pathway caused by specific activator SRT 1720 resulted in elevating autophagy/mitophagy related markers and SIRT1 inhibitor EX 527 reversed these effects. Additionally, SIRT1 activation significantly suppressed the ROS generation, leading to increase mitochondrial membrane potential and COX IV expression. Most importantly, the expression of tight junction molecules contributing to maintain intestinal barrier integrity was significantly up-regulated. Collectively, these findings indicated that autophagy/mitophagy elevation caused by SIRT1/PGC-1α pathway activation might be a protective mechanism to increase tight junction integrity against oxidative stress-mediated ROS production in IPEC-1 cells.
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Affiliation(s)
- Danyang Liang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Yisha Zhuo
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Zeheng Guo
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Lihua He
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Xueyi Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Yulong He
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Lexing Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
| | - Hanchuan Dai
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
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44
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Bykov VN, Grebenyuk AN, Ushakov IB. The Use of Radioprotective Agents to Prevent Effects Associated with Aging. BIOL BULL+ 2019. [DOI: 10.1134/s1062359019120021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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45
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Michaelidesová A, Konířová J, Bartůněk P, Zíková M. Effects of Radiation Therapy on Neural Stem Cells. Genes (Basel) 2019; 10:E640. [PMID: 31450566 PMCID: PMC6770913 DOI: 10.3390/genes10090640] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/19/2019] [Accepted: 08/22/2019] [Indexed: 12/29/2022] Open
Abstract
Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed.
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Affiliation(s)
- Anna Michaelidesová
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic
- Department of Radiation Dosimentry, Nuclear Physics Institute of the Czech Academy of Sciences, v. v. i., Na Truhlářce 39/64, 180 00 Prague 8, Czech Republic
| | - Jana Konířová
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic
- Department of Radiation Dosimentry, Nuclear Physics Institute of the Czech Academy of Sciences, v. v. i., Na Truhlářce 39/64, 180 00 Prague 8, Czech Republic
| | - Petr Bartůněk
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic
| | - Martina Zíková
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
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Ocolotobiche EE, Banegas YC, Güerci AM. Modulation of ionizing radiation-induced damage in human blood lymphocytes by in vivo treatment with resveratrol. Int J Radiat Biol 2019; 95:1220-1225. [PMID: 31140903 DOI: 10.1080/09553002.2019.1625489] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Purpose: Radiotherapy is an effective tool for cancer control, but side effects on normal tissue limit its therapeutic effectiveness. Thus, the search for agents that may allow the use of high doses of radiation but exerting a differential protection to healthy tissue is of current concern. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) (RSV) is a polyphenol with pleiotropic benefits for health due to its antioxidant and anti-inflammatory properties. Recent findings suggest that RSV could be promising in the fight against cancer since it inhibits the growth of tumor cells and optimizes radiotherapy. However, evidence in rodents and human beings is inconsistent. The aim of this study was to evaluate the radiomodulatory capacity of RSV on human lymphocytes. Materials and methods: To study these properties of RSV, human peripheral blood lymphocytes from 20 healthy women undergoing in vivo RSV treatment with 50 mg/day doses were irradiated. The genotoxic damage was assessed by the comet assay, also called single cell gel electrophoresis (it makes it possible to measure the extent of the DNA migration from individual cells, detecting the genomic damage present in each cell). Results: No differences were observed in basal clastogenic damage among samples without irradiation. There was only a slight radiation-induced clastogenic damage. The damage index (DI) value had a statistically significant increase in the exposed groups in comparison with the control groups (p < .0001), but a statistically significant decrease of the DI value was observed in samples irradiated after treatment with RSV compared to pretreatment samples (p < .0001). Conclusion: The RSV used as a dietary supplement had radioprotective properties, without exerting a cytotoxic effect. The potential utility of RSV to optimize the radiotherapeutic ratio in cancer treatments using radiotherapy should be considered.
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Affiliation(s)
- Eliana Evelina Ocolotobiche
- Faculty of Veterinary Sciences, IGEVET Institute of Veterinary Genetics "Ing. Fernando N. Dulout" (UNLP-CONICET LA PLATA) National University of La Plata , Buenos Aires , Argentina.,Faculty of Exact Sciences, National University of La Plata , Buenos Aires , Argentina.,Terapia Radiante S.A. Red CIO - La Plata , Buenos Aires , Argentina
| | - Yuliana Catalina Banegas
- Faculty of Veterinary Sciences, IGEVET Institute of Veterinary Genetics "Ing. Fernando N. Dulout" (UNLP-CONICET LA PLATA) National University of La Plata , Buenos Aires , Argentina.,Terapia Radiante S.A. Red CIO - La Plata , Buenos Aires , Argentina
| | - Alba Mabel Güerci
- Faculty of Veterinary Sciences, IGEVET Institute of Veterinary Genetics "Ing. Fernando N. Dulout" (UNLP-CONICET LA PLATA) National University of La Plata , Buenos Aires , Argentina.,Faculty of Exact Sciences, National University of La Plata , Buenos Aires , Argentina.,Terapia Radiante S.A. Red CIO - La Plata , Buenos Aires , Argentina
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Zhang W, Zhao T, Zhao Y, Gui D, Xu Y. Advanced Glycation End Products in Chinese Medicine Mediated Aging Diseases: A Review. Curr Vasc Pharmacol 2019; 18:322-333. [PMID: 31060489 DOI: 10.2174/1570161117666190507112157] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 04/11/2019] [Accepted: 04/12/2019] [Indexed: 12/25/2022]
Abstract
Aging has become a worldwide problem. During this process, the incidence of related diseases such as diabetes and atherosclerosis increases dramatically. Studies within the most recent two decades suggest a pivotal role of Advanced Glycation End Products (AGEs) in the aging process. This review aims to systemically summarize the effects and potential mechanism of Chinese Medicines on inhibiting AGEs-related aging diseases.
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Affiliation(s)
- Wenqian Zhang
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao SAR, China
| | - Tingting Zhao
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao SAR, China
| | - Yonghua Zhao
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao SAR, China.,Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macao SAR, China
| | - Dingkun Gui
- Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Youhua Xu
- Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao SAR, China
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Banegas YC, Ocolotobiche EE, Padula G, Córdoba EE, Fernández E, Güerci AM. Evaluation of resveratrol radiomodifying potential for radiotherapy treatment. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2018; 836:79-83. [DOI: 10.1016/j.mrgentox.2018.06.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 04/03/2018] [Accepted: 06/01/2018] [Indexed: 02/06/2023]
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Beneficial Effects of Resveratrol Administration-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions. Nutrients 2018; 10:nu10111813. [PMID: 30469326 PMCID: PMC6266814 DOI: 10.3390/nu10111813] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/08/2018] [Accepted: 11/14/2018] [Indexed: 12/15/2022] Open
Abstract
Resveratrol (RV) is a natural non-flavonoid polyphenol and phytoalexin produced by a number of plants such as peanuts, grapes, red wine and berries. Numerous in vitro studies have shown promising results of resveratrol usage as antioxidant, antiplatelet or anti-inflammatory agent. Beneficial effects of resveratrol activity probably result from its ability to purify the body from ROS (reactive oxygen species), inhibition of COX (cyclooxygenase) and activation of many anti-inflammatory pathways. Administration of the polyphenol has a potential to slow down the development of CVD (cardiovascular disease) by influencing on certain risk factors such as development of diabetes or atherosclerosis. Resveratrol induced an increase in Sirtuin-1 level, which by disrupting the TLR4/NF-κB/STAT signal cascade (toll-like receptor 4/nuclear factor κ-light-chain enhancer of activated B cells/signal transducer and activator of transcription) reduces production of cytokines in activated microglia. Resveratrol caused an attenuation of macrophage/mast cell-derived pro-inflammatory factors such as PAF (platelet-activating factor), TNF-α (tumour necrosis factor-α and histamine. Endothelial and anti-oxidative effect of resveratrol may contribute to better outcomes in stroke management. By increasing BDNF (brain-derived neurotrophic factor) serum concentration and inducing NOS-3 (nitric oxide synthase-3) activity resveratrol may have possible therapeutical effects on cognitive impairments and dementias especially in those characterized by defective cerebrovascular blood flow.
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Resveratrol Boosts Cognitive Function by Targeting SIRT1. Neurochem Res 2018; 43:1705-1713. [DOI: 10.1007/s11064-018-2586-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Revised: 05/13/2018] [Accepted: 06/21/2018] [Indexed: 01/15/2023]
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