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Phuong LDT, Thien LC, Su Pham CD, Minh NU, Huy Bao NT, Thien Truc LN, Huyen TTN, Minh DT, Nguyen NT, Van Thuan N, Bui HT. Melatonin and cyclic adenosine monophosphate enhance the meiotic and developmental competence of porcine oocytes from early antral follicles during in vitro growth and pre-maturation culture. Theriogenology 2025; 237:129-142. [PMID: 40015084 DOI: 10.1016/j.theriogenology.2025.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/13/2025] [Accepted: 02/21/2025] [Indexed: 03/01/2025]
Abstract
Melatonin has been studied for its ability to improve oocyte quality and modulate cyclic adenosine monophosphate (cAMP) production. However, the effects of melatonin on the in vitro growth (IVG) of oocyte-cumulus-granulosa complexes (OCGCs) derived from early antral follicles (EAFs) have not been fully investigated. This study aimed to examine the effects of melatonin during IVG on the developmental competence and blastocyst quality of porcine oocytes isolated from EAFs. In addition, the combination of melatonin with dibutyl cAMP (Mela + dbcAMP) or hypoxanthine (Mela + HX) during IVG and pre-in vitro maturation (pre-IVM) was also investigated. The result showed that the modified medium supplemented with 10 μM melatonin after 4-day IVG enhanced antrum formation, survival rate, and oocyte diameter, especially, the melatonin-treated group enhanced expression of histone acetylation (Ac-H3-K9) higher than the untreated group. In addition, the combination of 10 μM melatonin with dbcAMP during IVG and during 7h of pre-IVM had significantly improved meiotic competence and cumulus expansion after IVM compared to Mela + HX groups. Finally, the combination of Mela + dbcAMP improved parthenogenetic blastocyst formation rather than the untreated group, and expression of histone methylation (Me-H3-K4) and Ac-H3-K9 in blastocyst comparable group derived from oocytes of large antral follicles (LAFs). Furthermore, melatonin with concentrations of 10 μM and 100 μM during IVG enhanced expression of pluripotency gene-related (OCT4, NANOG, SOX2) and balance cell viability via apoptosis-related gene (BCL2/BAX). In conclusion, melatonin combined with dbcAMP during IVG and pre-IVM of oocytes derived from EAFs demonstrated superior efficacy in enhancing oocyte growth, maturation, and development of porcine pre-implantation embryos.
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Affiliation(s)
- Lam Do Truc Phuong
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Lam Chi Thien
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Cao Dang Su Pham
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Nguyen Uyen Minh
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Nguyen Thai Huy Bao
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Le Nguyen Thien Truc
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Truong Thi Ngoc Huyen
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Do Tu Minh
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam
| | - Nhat-Thinh Nguyen
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam; University of Health Sciences-VNU, Ho Chi Minh City, 70000, Viet Nam
| | - Nguyen Van Thuan
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam.
| | - Hong-Thuy Bui
- Cellular Reprogramming Lab, School of Biotechnology, International University, Ho Chi Minh City, 70000, Viet Nam; Vietnam National University, Ho Chi Minh City, 70000, Viet Nam.
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Bonilla-Vidal L, Espina M, García ML, Baldomà L, Badia J, Gliszczyńska A, Souto EB, Sánchez-López E. Combination of Apigenin and Melatonin with nanostructured lipid carriers as anti-inflammatory ocular treatment. Int J Pharm 2025; 670:125160. [PMID: 39746583 DOI: 10.1016/j.ijpharm.2024.125160] [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: 11/21/2024] [Revised: 12/28/2024] [Accepted: 12/30/2024] [Indexed: 01/04/2025]
Abstract
Ocular inflammation is a complex pathology with limited treatment options. While traditional therapies have side effects, novel approaches, such as natural compounds like Apigenin (APG) and Melatonin (MEL) offer promising solutions. APG and MEL, in combination with nanostructured lipid carriers (NLC), may provide a synergistic effect in treating ocular inflammation, potentially improving patient outcomes and reducing adverse effects. NLC could provide chemical protection of these compounds, while offering a sustained release into the ocular surface. Optimized NLC exhibited suitable physicochemical parameters, physical stability, sustained release of APG and MEL, and were biocompatible in vitro with a corneal cell line, and in ovo by using hen's egg chorioallantoic membrane test. In vitro and in vivo studies confirmed the NLC' ability to attenuate inflammation by reducing interleukin-6 (IL-6), IL-8 and monocyte chemoattractant protein 1 (MCP-1) cytokine levels and by decreasing inflammation in a rabbit model. These findings suggest that the co-encapsulation of APG and MEL into NLC could represent a promising strategy for managing ocular inflammatory conditions.
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Affiliation(s)
- Lorena Bonilla-Vidal
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN(2)UB), University of Barcelona, 08028 Barcelona, Spain
| | - Marta Espina
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN(2)UB), University of Barcelona, 08028 Barcelona, Spain
| | - María Luisa García
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN(2)UB), University of Barcelona, 08028 Barcelona, Spain
| | - Laura Baldomà
- Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Institute of Research of Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain
| | - Josefa Badia
- Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Institute of Research of Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain
| | - Anna Gliszczyńska
- Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland
| | - Eliana B Souto
- UCD School of Chemical and Bioprocess Engineering, University College Dublin, Belfield D04 V1W8, Ireland
| | - Elena Sánchez-López
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN(2)UB), University of Barcelona, 08028 Barcelona, Spain.
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Kilinc E, Torun IE, Baranoglu Kilinc Y, Töre F. Proposed receptor-mediated mechanisms of melatonin in nitroglycerin-induced migraine-like hyperalgesic conditions in rats. J Nutr Biochem 2025; 136:109800. [PMID: 39537039 DOI: 10.1016/j.jnutbio.2024.109800] [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: 08/06/2024] [Revised: 10/23/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
Melatonin has a therapeutic effect on migraine, but the mechanisms underlying its antimigraine effect have not been elucidated. This study therefore investigated for the first time the receptor-mediated mechanisms of action of melatonin in nitroglycerin (NTG)- induced migraine-like hyperalgesic conditions in rats. Melatonin, nonselective MT1/MT2 antagonist luzindole, selective MT2 antagonist DH97 or potent MT3 antagonist prazosin, alone or in various combinations, were administered to NTG-induced migraine rats and ex-vivo meningeal preparations. Basal and drug-treated pain behaviors were assessed with the von-Frey test. CGRP levels in the trigeminal ganglia, trigeminal nucleus caudalis (TNC) and ex-vivo superfusate medium, as well as c-fos level in the TNC, were measured by ELISA. Meningeal mast cells were stained with toluidine-blue and examined histologically for their activation and count. Melatonin mitigated mechanical hyperalgesia, and c-fos and CGRP expression in the TNC, CGRP expression in trigeminal ganglia, CGRP release from meningeal afferents, all of which were induced by NTG, and also suppressed NTG-stimulated meningeal mast cell activation. The effects of melatonin were abolished in the presence of luzindole and DH97, respectively. However, prazosin did not reverse the effects of melatonin except for mechanical hyperalgesia. Luzindole and DH97 in combinations with prazosin also canceled the effects of melatonin, respectively, other than CGRP expression in the TNC. Melatonin exerts its anti-hyperalgesic effects through modulation of trigeminal expression and meningeal release of CGRP, and meningeal mast cell activation in experimental migraine-like conditions. The effects of melatonin are mainly mediated by MT2 receptors, without excluding a possible role for MT1.
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Affiliation(s)
- Erkan Kilinc
- Department of Physiology, Bolu Abant Izzet Baysal University, Medical Faculty, Bolu, Türkiye.
| | - Ibrahim Ethem Torun
- Department of Physiology, Bolu Abant Izzet Baysal University, Medical Faculty, Bolu, Türkiye
| | | | - Fatma Töre
- Department of Physiology, Atlas University, Medical Faculty, Istanbul, Türkiye
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Yu HR, Tsai CY, Chen WL, Liu PY, Tain YL, Sheen JM, Huang YS, Tiao MM, Chiu CY. Exploring Oxidative Stress and Metabolic Dysregulation in Lung Tissues of Offspring Rats Exposed to Prenatal Polystyrene Microplastics: Effects of Melatonin Treatment. Antioxidants (Basel) 2024; 13:1459. [PMID: 39765788 PMCID: PMC11672973 DOI: 10.3390/antiox13121459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 11/21/2024] [Accepted: 11/24/2024] [Indexed: 01/11/2025] Open
Abstract
Metabolomics research provides a clearer understanding of an organism's metabolic state and enables a more accurate representation of its functional performance. This study aimed to investigate changes in the metabolome of lung tissues resulting from prenatal exposure to polystyrene microplastics (PS-MPs) and to understand the underlying mechanisms of lung damage in rat offspring. We conducted metabolomic analyses of lung tissue from seven-day-old rat pups exposed to prenatal PS-MPs. Our findings revealed that prenatal exposure to PS-MPs led to significantly increased oxidative stress in lung tissues, characterized by notable imbalances in nucleic acid metabolism and altered profiles of specific amino acids. Furthermore, we evaluated the therapeutic effects of melatonin treatment on lung function in 120-day-old offspring and found that melatonin treatment significantly improved lung function and histologic change in the affected offspring. This study provides valuable biological insights into the mechanisms underlying lung damage caused by prenatal PS-MPs exposure. Future studies should focus on validating the results of animal experiments in humans, exploring additional therapeutic mechanisms of melatonin, and developing suitable protocols for clinical use.
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Affiliation(s)
- Hong-Ren Yu
- Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (H.-R.Y.); (W.-L.C.); (Y.-L.T.); (J.-M.S.); (Y.-S.H.)
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- Institute for Translational Research in Biomedicine, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
| | - Ching-Yi Tsai
- Institute for Translational Research in Biomedicine, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
| | - Wei-Ling Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (H.-R.Y.); (W.-L.C.); (Y.-L.T.); (J.-M.S.); (Y.-S.H.)
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Po-Yu Liu
- School of Medicine, College of Medicine, The Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung 807, Taiwan;
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - You-Lin Tain
- Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (H.-R.Y.); (W.-L.C.); (Y.-L.T.); (J.-M.S.); (Y.-S.H.)
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- Institute for Translational Research in Biomedicine, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
| | - Jiunn-Ming Sheen
- Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (H.-R.Y.); (W.-L.C.); (Y.-L.T.); (J.-M.S.); (Y.-S.H.)
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yi-Siang Huang
- Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (H.-R.Y.); (W.-L.C.); (Y.-L.T.); (J.-M.S.); (Y.-S.H.)
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Mao-Meng Tiao
- Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (H.-R.Y.); (W.-L.C.); (Y.-L.T.); (J.-M.S.); (Y.-S.H.)
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chih-Yung Chiu
- Division of Pediatric Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan 333, Taiwan
- Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
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Haider KH. Melatonin-based priming of stem cells to alleviate oxidative stress. World J Stem Cells 2024; 16:985-989. [DOI: 10.4252/wjsc.v16.i11.985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 09/28/2024] [Accepted: 10/18/2024] [Indexed: 11/26/2024] Open
Abstract
Stem cell expansion in vitro and transplantation in the cytokine-rich proinflammatory milieu in the injured tissue generate immense oxidative stress that interferes with the cells’ survival, stemness, and repairability. Stem cell priming has gained popularity to overcome these issues. Given melatonin’s oxidative-scavenging properties, Gu et al have used periodontal ligament stem cells cultured under oxidative stress as an in vitro model to study the cytoprotective effects of melatonin. Our letter to the editor delves into melatonin-induced stem cell priming and the underlying molecular mechanism, focusing on the intriguing role of Yes-associated protein signaling in alleviating oxidative stress. We stress the importance of understanding the distinction between in vitro and in vivo oxidative stress conditions, a crucial aspect of stem cell research that invokes a sense of critical thinking in the readership. The study by Gu et al presents a novel approach to oxidative stress management, offering exciting possibilities for future research and applications.
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Affiliation(s)
- Khawaja Husnain Haider
- Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, AlQaseem, Saudi Arabia
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Paydaş Hataysal E, Körez MK, Guler EM, Vatansev H, Bozalı K, Basaranoglu M, Vatansev H. Impaired Kynurenine Pathway in Inflammatory Bowel Disease. J Clin Med 2024; 13:6147. [PMID: 39458097 PMCID: PMC11508637 DOI: 10.3390/jcm13206147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 10/08/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Inflammatory bowel diseases primarily encompass Crohn's disease and ulcerative colitis. Insufficient levels of tryptophan cause an imbalance in the gut microbiota, leading to inflammation in the gastrointestinal tract. The main catabolic pathway of tryptophan is the kynurenine pathway. Our study aims to evaluate serum tryptophan, the kynurenine pathway, and oxidative stress parameters, including total oxidant status and total antioxidant capacity, in patients with Crohn's disease and ulcerative colitis. Methods: The study included 80 follow-up patients in remission diagnosed with Crohn's disease and ulcerative colitis who attended the Gastroenterology Outpatient Clinic, as well as 78 healthy controls. Serum tryptophan, kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and kynurenic acid levels were measured with liquid chromatography and tandem mass spectrometry (LC-MS/MS). All statistical analysis was performed using R version 4.2.1. Statistical Language. Results: Serum tryptophan, 3-hydroxyanthranilic acid, and total antioxidant capacity were lower in patients with ulcerative colitis and Crohn's disease compared to those in the control group. The serum total oxidant status in the control group was significantly lower than in patients with Crohn's disease and ulcerative colitis. Conclusions: The results of our research indicate that tryptophan and kynurenine pathway metabolites could potentially contribute to the pathogenesis of inflammatory bowel diseases.
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Affiliation(s)
- Esra Paydaş Hataysal
- Department of Biochemistry, Göztepe Prof. Dr. Süleyman Yalçın City Hospital, 34722 Istanbul, Türkiye
| | - Muslu Kazım Körez
- Department of Biostatistics, Faculty of Medicine, Selcuk University, 42250 Konya, Türkiye
| | - Eray Metin Guler
- Department of Biochemistry, Hamidiye Faculty of Medicine, University of Health Sciences, 34480 Istanbul, Türkiye
| | - Hakan Vatansev
- Department of Food Processing, Meram Vocational School, Necmettin Erbakan University, 42092 Konya, Türkiye
| | - Kubra Bozalı
- Department of Biochemistry, Hamidiye Faculty of Medicine, University of Health Sciences, 34480 Istanbul, Türkiye
| | - Metin Basaranoglu
- Department of Gastroenterology, Faculty of Medicine, Bezmialem University, 34093 Istanbul, Türkiye
| | - Husamettin Vatansev
- Department of Biochemistry, Faculty of Medicine, Selcuk University, 42250 Konya, Türkiye
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Sohn EH, Kim SN, Lee SR. Melatonin's Impact on Wound Healing. Antioxidants (Basel) 2024; 13:1197. [PMID: 39456451 PMCID: PMC11504849 DOI: 10.3390/antiox13101197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 09/30/2024] [Accepted: 10/01/2024] [Indexed: 10/28/2024] Open
Abstract
Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, such as the skin and intestines. Melatonin's effects in target tissues can be mediated through receptor-dependent mechanisms. Additionally, melatonin exerts various actions via receptor-independent pathways. In biological systems, melatonin and its endogenous metabolites often produce similar effects. While injuries are common in daily life, promoting optimal wound healing is essential for patient well-being and healthcare outcomes. Beyond regulating circadian rhythms as a neuroendocrine hormone, melatonin may enhance wound healing through (1) potent antioxidant properties, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, and (6) anti-pruritic (anti-itch) effects. This review aims to provide a comprehensive overview of scientific studies that demonstrate melatonin's potential roles in supporting effective wound healing.
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Affiliation(s)
- Eun-Hwa Sohn
- Department of Bio-Health Convergence, Kangwon National University, Chuncheon 24341, Republic of Korea;
| | - Su-Nam Kim
- Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea
| | - Sung-Ryul Lee
- Department of Convergence Biomedical Science, Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Busan 47392, Republic of Korea
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Xu Y, Zhang S, Bao Y, Luan J, Fu Z, Sun M, Zhao X, Feng X. Melatonin protects zebrafish pancreatic development and physiological rhythms from sodium propionate-induced disturbances via the hypothalamic-pituitary-thyroid axis. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:7454-7463. [PMID: 38717324 DOI: 10.1002/jsfa.13565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 03/30/2024] [Accepted: 04/25/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND The widespread use of sodium propionate as a preservative in food may affect public health. We aimed to assess the effects of sodium propionate on circadian rhythms and pancreatic development in zebrafish and the possible underlying mechanisms. RESULTS In this experiment, we analyzed the relationship between circadian rhythms and pancreatic development and then revealed the role of the thyroid endocrine system in zebrafish. The results showed that sodium propionate interfered with the rhythmic behavior of zebrafish, and altered the expression of important rhythmic genes. Experimental data revealed that pancreatic morphology and developmental genes were altered after sodium propionate exposure. Additionally, thyroid hormone levels and key gene expression associated with the hypothalamic-pituitary-thyroid axis were significantly altered. Melatonin at a concentration of 1 μmol L-1, with a mild effect on zebrafish, observably alleviated sodium propionate-induced disturbances in circadian rhythms and pancreatic development, as well as regulating the thyroid system. CONCLUSION Melatonin, while modulating the thyroid system, significantly alleviates sodium propionate-induced circadian rhythm disturbances and pancreatic developmental disorders. We further revealed the deleterious effects of sodium propionate as well as the potential therapeutic effects of melatonin on circadian rhythm, pancreatic development and the thyroid system. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Yixin Xu
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Shuhui Zhang
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Yehua Bao
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Jialu Luan
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Zhenhua Fu
- Institute of Robotics and Automatic Information System, College of Artificial Intelligence, Nankai University, Tianjin, China
| | - Mingzhu Sun
- Institute of Robotics and Automatic Information System, College of Artificial Intelligence, Nankai University, Tianjin, China
| | - Xin Zhao
- Institute of Robotics and Automatic Information System, College of Artificial Intelligence, Nankai University, Tianjin, China
| | - Xizeng Feng
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
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An X, Yu W, Liu J, Tang D, Yang L, Chen X. Oxidative cell death in cancer: mechanisms and therapeutic opportunities. Cell Death Dis 2024; 15:556. [PMID: 39090114 PMCID: PMC11294602 DOI: 10.1038/s41419-024-06939-5] [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: 03/08/2024] [Revised: 07/19/2024] [Accepted: 07/22/2024] [Indexed: 08/04/2024]
Abstract
Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse cellular functions, including cell signaling and immune responses. However, a disturbance in the balance between ROS production and cellular antioxidant defenses can lead to an excessive ROS buildup, causing oxidative stress. This stress damages essential cellular components, including lipids, proteins, and DNA, potentially culminating in oxidative cell death. This form of cell death can take various forms, such as ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis, each displaying distinct genetic, biochemical, and signaling characteristics. The investigation of oxidative cell death holds promise for the development of pharmacological agents that are used to prevent tumorigenesis or treat established cancer. Specifically, targeting key antioxidant proteins, such as SLC7A11, GCLC, GPX4, TXN, and TXNRD, represents an emerging approach for inducing oxidative cell death in cancer cells. This review provides a comprehensive summary of recent progress, opportunities, and challenges in targeting oxidative cell death for cancer therapy.
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Affiliation(s)
- Xiaoqin An
- Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, PR China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, Guizhou, PR China
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, PR China
| | - Wenfeng Yu
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, Guizhou, PR China
| | - Jinbao Liu
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
| | - Li Yang
- Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, PR China.
| | - Xin Chen
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, PR China.
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China.
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Abdallah N, Amer ME, Amer MA, El-Missiry MA, Othman AI. Melatonin mitigated methotrexate-induced hepatotoxicity through interrelated biological processes. Mol Biol Rep 2024; 51:833. [PMID: 39039363 DOI: 10.1007/s11033-024-09792-z] [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: 06/14/2024] [Accepted: 07/09/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND Hepatotoxicity associated with methotrexate (MTX) is mainly due to disruption of redox balance and development of oxidative injury to hepatocytes. Melatonin (MLT) is a potent antioxidant and regulates wide range of biological functions, processes and utilized as adjuvant for number of medical applications. The current study investigated the mitigating effect of MLT on the MTX-induced hepatotoxicity. METHODS AND RESULTS Adult male rats received MLT (25 mg/kg, orally) for seven days flowed by single injection of MTX (20 mg/kg, ip) then treat with MLT continued for additional 7 days. The present result showed MLT treatment mitigated histopathological changes in the liver that associated with normalization of ALT and AST activity as well as bilirubin, albumin and alfa-fetoprotein levels in serum of MLT + MTX-treated rat to comparable control level. MLT treatment significantly reduced MDA content and myeloperoxidase activity while enhanced the activity of superoxide dismutase, catalase and glutathione content in the liver indicating the empowerment of the antioxidant status. Amelioration of MLT-induced oxidative stress resulted in a reduction in the inflammatory response due to antioxidant restoration and inhibited apoptosis indicated by downregulation of caspase-3 expression. The replenishment of antioxidant content powers the defense system of the hepatocytes. As a result, apoptosis is reduced which might be due to the ability of MLT protect DNA integrity thus maintaining hepatocyte functions and structure. Consequently, liver histology was protected. CONCLUSIONS In summary, MLT modulates liver function and structure by orchestrating linked processes, including redox balance, inflammatory response, suppression of caspase-3, and DNA damage.
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Affiliation(s)
- Noura Abdallah
- Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Maggie E Amer
- Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Maher A Amer
- Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt
| | | | - Azza I Othman
- Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt.
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11
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Qutifan S, Saleh T, Abu Shahin N, ELBeltagy M, Obeidat F, Qattan D, Kalbouneh H, Barakat NA, Alsalem M. Melatonin mitigates cisplatin-induced cognitive impairment in rats and improves hippocampal dendritic spine density. Neuroreport 2024; 35:657-663. [PMID: 38813907 DOI: 10.1097/wnr.0000000000002049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
Cisplatin-induced cognitive impairment (chemobrain) affects a considerable percentage of cancer patients and has no established pharmacological treatment. Chemobrain can be associated with neuroinflammation and oxidative stress. Melatonin, a pineal hormone, is known to have antioxidant, anti-inflammatory and neuroprotective potential. In this study, we investigated cisplatin-induced cognitive impairment in rats and whether melatonin can improve or reverse this impairment. Behavioral testing involved measuring working memory using the novel location recognition test (NLRT) under conditions of cisplatin or cisplatin + melatonin treatment, followed by the collection of rats' brains. The brains were subsequently stained with Golgi-Cox stain and then the hippocampus area CA3 of each one was examined, and dendritic spine density was calculated. Treatment with cisplatin resulted in deficits in the rats' performance in the NLRT (P < 0.05). These deficits were prevented by the coadministration of melatonin (P < 0.05). Cisplatin also reduced the density of dendritic spines in the hippocampus (P < 0.0001), specifically CA3 area, while the coadministration of melatonin significantly reversed this reduction (P < 0.001). This study showed that melatonin can ameliorate cisplatin-induced spatial memory deficits and dendritic spines density abnormalities in rats. Given that melatonin is a safe and wildly used supplement, it is feasible to explore its use as a palliative intervention in cancer treatment.
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Affiliation(s)
- Shahd Qutifan
- Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman
| | - Tareq Saleh
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa
| | - Nisreen Abu Shahin
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan
| | - Maha ELBeltagy
- Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman
- Human Anatomy and Embryology, Faculty of Medicine, Menoufia University, Shibin El Kom, Egypt
| | - Fatimah Obeidat
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan
| | - Duaa Qattan
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan
| | - Heba Kalbouneh
- Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman
| | - Noor A Barakat
- Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Middle East University, Amman, Jordan
| | - Mohammad Alsalem
- Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman
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12
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Giri A, Mehan S, Khan Z, Das Gupta G, Narula AS, Kalfin R. Modulation of neural circuits by melatonin in neurodegenerative and neuropsychiatric disorders. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:3867-3895. [PMID: 38225412 DOI: 10.1007/s00210-023-02939-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 12/30/2023] [Indexed: 01/17/2024]
Abstract
Neurodegenerative and neuropsychiatric disorders are two broad categories of neurological disorders characterized by progressive impairments in movement and cognitive functions within the central and peripheral nervous systems, and have emerged as a significant cause of mortality. Oxidative stress, neuroinflammation, and neurotransmitter imbalances are recognized as prominent pathogenic factors contributing to cognitive deficits and neurobehavioral anomalies. Consequently, preventing neurodegenerative and neuropsychiatric diseases has surfaced as a pivotal challenge in contemporary public health. This review explores the investigation of neurodegenerative and neuropsychiatric disorders using both synthetic and natural bioactive compounds. A central focus lies on melatonin, a neuroregulatory hormone secreted by the pineal gland in response to light-dark cycles. Melatonin, an amphiphilic molecule, assumes multifaceted roles, including scavenging free radicals, modulating energy metabolism, and synchronizing circadian rhythms. Noteworthy for its robust antioxidant and antiapoptotic properties, melatonin exhibits diverse neuroprotective effects. The inherent attributes of melatonin position it as a potential key player in the pathophysiology of neurological disorders. Preclinical and clinical studies have demonstrated melatonin's efficacy in alleviating neuropathological symptoms across neurodegenerative and neuropsychiatric conditions (depression, schizophrenia, bipolar disorder, and autism spectrum disorder). The documented neuroprotective prowess of melatonin introduces novel therapeutic avenues for addressing neurodegenerative and psychiatric disorders. This comprehensive review encompasses many of melatonin's applications in treating diverse brain disorders. Despite the strides made, realizing melatonin's full neuroprotective potential necessitates further rigorous clinical investigations. By unravelling the extended neuroprotective benefits of melatonin, future studies promise to deepen our understanding and augment the therapeutic implications against neurological deficits.
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Affiliation(s)
- Aditi Giri
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy Moga, Punjab, India
| | - Sidharth Mehan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy Moga, Punjab, India.
- IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India.
| | - Zuber Khan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy Moga, Punjab, India
- IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India
| | | | - Acharan S Narula
- Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC, 27516, USA
| | - Reni Kalfin
- Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, Sofia, 1113, Bulgaria
- Department of Healthcare, South-West University "NeofitRilski", Ivan Mihailov St. 66, Blagoevgrad, 2700, Bulgaria
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13
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Mohammed AI, Fedoruk L, Fisher N, Liu AX, Khanna S, Naylor K, Gong Z, Celentano A, Alrashdan MS, Cirillo N. Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials. Biomolecules 2024; 14:560. [PMID: 38785967 PMCID: PMC11117894 DOI: 10.3390/biom14050560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 05/25/2024] Open
Abstract
Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.
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Affiliation(s)
- Ali I. Mohammed
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Lexi Fedoruk
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Nicholas Fisher
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Andy Xiaoqian Liu
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Samar Khanna
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Kaelan Naylor
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Ziyi Gong
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Antonio Celentano
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Mohammad S. Alrashdan
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates;
- Department of Oral Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Nicola Cirillo
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
- School of Dentistry, University of Jordan, Amman 11942, Jordan
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14
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Hakami AY, Alghamdi BS, Alshehri FS. Exploring the potential use of melatonin as a modulator of tramadol-induced rewarding effects in rats. Front Pharmacol 2024; 15:1373746. [PMID: 38738177 PMCID: PMC11082292 DOI: 10.3389/fphar.2024.1373746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 04/08/2024] [Indexed: 05/14/2024] Open
Abstract
Background Melatonin is responsible for regulating the sleep-wake cycle and circadian rhythms in mammals. Tramadol, a synthetic opioid analgesic, is used to manage moderate to severe pain but has a high potential for abuse and dependence. Studies have shown that melatonin could be a potential modulator to reduce tramadol addiction. Methods Male Wistar rats were used to investigate the effect of melatonin on tramadol-induced place preference. The rats were divided into four groups: control, tramadol, tramadol + melatonin (single dose), and tramadol + melatonin (repeated doses). Tramadol was administered intraperitoneally at 40 mg/kg, while melatonin was administered at 50 mg/kg for both the single dose and repeated-dose groups. The study consisted of two phases: habituation and acquisition. Results Tramadol administration produced conditioned place preference (CPP) in rats, indicating rewarding effects. However, melatonin administration blocked tramadol-induced CPP. Surprisingly, repeated doses of melatonin were ineffective and did not reduce the expression of CPP compared to that of the single dose administration. Conclusion The study suggests that melatonin may be a potential therapeutic option for treating tramadol addiction. The results indicate that melatonin attenuates the expression of tramadol-induced CPP, supporting its uses as an adjunct therapy for managing tramadol addiction. However, further studies are needed to investigate its effectiveness in humans.
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Affiliation(s)
- Alqassem Y. Hakami
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Badrah S. Alghamdi
- Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Fahad S. Alshehri
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
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15
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Rieder GS, Braga MM, Mussulini BHM, Silva ES, Lazzarotto G, Casali EA, Oliveira DL, Franco JL, Souza DOG, Rocha JBT. Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia. Neurotox Res 2024; 42:13. [PMID: 38332435 DOI: 10.1007/s12640-024-00691-6] [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: 08/09/2023] [Revised: 01/09/2024] [Accepted: 01/17/2024] [Indexed: 02/10/2024]
Abstract
Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)2 effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.
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Affiliation(s)
- Guilherme S Rieder
- Programa de Pós Graduação Em Bioquímica Toxicológica, Departamento de Bioquímica E Biologia Molecular, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Avenida Roraima 1000, Santa Maria, RS, 97105-900, Brazil
| | - Marcos M Braga
- Programa de Pós Graduação Em Bioquímica Toxicológica, Departamento de Bioquímica E Biologia Molecular, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Avenida Roraima 1000, Santa Maria, RS, 97105-900, Brazil
| | - Ben Hur M Mussulini
- Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil
| | - Emerson S Silva
- Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil
| | - Gabriela Lazzarotto
- Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil
| | - Emerson André Casali
- Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil
| | - Diogo L Oliveira
- Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil
| | - Jeferson L Franco
- Universidade Federal Do Pampa, Campus São Gabriel, São Gabriel, RS, Brazil
| | - Diogo O G Souza
- Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil
| | - João Batista T Rocha
- Programa de Pós Graduação Em Bioquímica Toxicológica, Departamento de Bioquímica E Biologia Molecular, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Avenida Roraima 1000, Santa Maria, RS, 97105-900, Brazil.
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16
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Joseph TT, Schuch V, Hossack DJ, Chakraborty R, Johnson EL. Melatonin: the placental antioxidant and anti-inflammatory. Front Immunol 2024; 15:1339304. [PMID: 38361952 PMCID: PMC10867115 DOI: 10.3389/fimmu.2024.1339304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 01/15/2024] [Indexed: 02/17/2024] Open
Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free radical scavenger, circadian rhythm regulator, and sleep hormone. However, its most popular role is the ability to regulate sleep through the circadian rhythm. Interestingly, recent studies have shown that melatonin is an important and essential hormone during pregnancy, specifically in the placenta. This is primarily due to the placenta's ability to synthesize its own melatonin rather than depending on the pineal gland. During pregnancy, melatonin acts as an antioxidant and anti-inflammatory, which is necessary to ensure a stable environment for both the mother and the fetus. It is an essential antioxidant in the placenta because it reduces oxidative stress by constantly scavenging for free radicals, i.e., maintain the placenta's integrity. In a healthy pregnancy, the maternal immune system is constantly altered to accommodate the needs of the growing fetus, and melatonin acts as a key anti-inflammatory by regulating immune homeostasis during early and late gestation. This literature review aims to identify and summarize melatonin's role as a powerful antioxidant and anti-inflammatory that reduces oxidative stress and inflammation to maintain a favorable homeostatic environment in the placenta throughout gestation.
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Affiliation(s)
- Tyana T. Joseph
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
| | - Viviane Schuch
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
| | - Daniel J. Hossack
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
| | - Rana Chakraborty
- Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Erica L. Johnson
- Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States
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Samynathan A, Fishbein AB, Abbott SM, Booster GD, Zee PC, Sheldon SH, Yosipovitch G, Silverberg JI. Assessment and Management of Sleep Disturbances in Atopic Dermatitis: A Review. Dermatitis 2024; 35:S7-S12. [PMID: 37756222 DOI: 10.1089/derm.2023.0074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2023]
Abstract
Atopic dermatitis (AD) is a chronic burdensome inflammatory skin disease with well-established cutaneous and systemic comorbidities and disease burden. AD particularly has profound impacts on sleep in individuals of all ages. Sleep disturbances (SDs) affect 6.2% of school-age children and 33-87.1% of adults with AD. This narrative review addresses the burden of SD in AD patients, as well as biological mechanisms of SD in AD, including biological clocks influencing sleep, inflammation, and behavior. Approaches for early detection, diagnosis, objective quantification, patient education, and management are reviewed. It is imperative to break the itch-scratch cycle to reduce SDs and improve quality of life in individuals with AD.
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Affiliation(s)
- Archana Samynathan
- From the Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
| | - Anna B Fishbein
- Department of Allergy and Immunology, Robert and Anne Lurie Children's Hospital, Chicago, Illinois, USA
| | - Sabra M Abbott
- Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Genery D Booster
- Department of Pediatrics, National Jewish Hospital, Denver, Colorado, USA
| | - Phyllis C Zee
- Department of Sleep Medicine, Robert and Anne Lurie Children's Hospital, Chicago, Illinois, USA
| | - Stephen H Sheldon
- Sleep Medicine Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - Gil Yosipovitch
- Department of Dermatology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Jonathan I Silverberg
- Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
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Zhivodernikov IV, Kirichenko TV, Markina YV, Postnov AY, Markin AM. Molecular and Cellular Mechanisms of Osteoporosis. Int J Mol Sci 2023; 24:15772. [PMID: 37958752 PMCID: PMC10648156 DOI: 10.3390/ijms242115772] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 10/26/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
Osteoporosis is a widespread systemic disease characterized by a decrease in bone mass and an imbalance of the microarchitecture of bone tissue. Experimental and clinical studies devoted to investigating the main pathogenetic mechanisms of osteoporosis revealed the important role of estrogen deficiency, inflammation, oxidative stress, cellular senescence, and epigenetic factors in the development of bone resorption due to osteoclastogenesis, and decreased mineralization of bone tissue and bone formation due to reduced function of osteoblasts caused by apoptosis and age-depended differentiation of osteoblast precursors into adipocytes. The current review was conducted to describe the basic mechanisms of the development of osteoporosis at molecular and cellular levels and to elucidate the most promising therapeutic strategies of pathogenetic therapy of osteoporosis based on articles cited in PubMed up to September 2023.
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Affiliation(s)
| | | | - Yuliya V. Markina
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, 119991 Moscow, Russia; (I.V.Z.); (T.V.K.); (A.Y.P.); (A.M.M.)
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Piekarska K, Bonowicz K, Grzanka A, Jaworski ŁM, Reiter RJ, Slominski AT, Steinbrink K, Kleszczyński K, Gagat M. Melatonin and TGF-β-Mediated Release of Extracellular Vesicles. Metabolites 2023; 13:metabo13040575. [PMID: 37110233 PMCID: PMC10142249 DOI: 10.3390/metabo13040575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/12/2023] [Accepted: 04/17/2023] [Indexed: 04/29/2023] Open
Abstract
The immune system, unlike other systems, must be flexible and able to "adapt" to fully cope with lurking dangers. The transition from intracorporeal balance to homeostasis disruption is associated with activation of inflammatory signaling pathways, which causes modulation of the immunology response. Chemotactic cytokines, signaling molecules, and extracellular vesicles act as critical mediators of inflammation and participate in intercellular communication, conditioning the immune system's proper response. Among the well-known cytokines allowing for the development and proper functioning of the immune system by mediating cell survival and cell-death-inducing signaling, the tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) are noteworthy. The high bloodstream concentration of those pleiotropic cytokines can be characterized by anti- and pro-inflammatory activity, considering the powerful anti-inflammatory and anti-oxidative stress capabilities of TGF-β known from the literature. Together with the chemokines, the immune system response is also influenced by biologically active chemicals, such as melatonin. The enhanced cellular communication shows the relationship between the TGF-β signaling pathway and the extracellular vesicles (EVs) secreted under the influence of melatonin. This review outlines the findings on melatonin activity on TGF-β-dependent inflammatory response regulation in cell-to-cell communication leading to secretion of the different EV populations.
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Affiliation(s)
- Klaudia Piekarska
- Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
| | - Klaudia Bonowicz
- Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
| | - Alina Grzanka
- Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
| | - Łukasz M Jaworski
- Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health, Long School of Medicine, San Antonio, TX 78229, USA
| | - Andrzej T Slominski
- Department of Dermatology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Pathology and Laboratory Medicine Service, VA Medical Center, Birmingham, AL 35294, USA
| | - Kerstin Steinbrink
- Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany
| | - Konrad Kleszczyński
- Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany
| | - Maciej Gagat
- Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
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20
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Păncescu FM, Rikabi AAKK, Oprea OC, Grosu AR, Nechifor AC, Grosu VA, Tanczos SK, Dumitru F, Nechifor G, Bungău SG. Chitosan-sEPDM and Melatonin-Chitosan-sEPDM Composite Membranes for Melatonin Transport and Release. MEMBRANES 2023; 13:282. [PMID: 36984671 PMCID: PMC10057635 DOI: 10.3390/membranes13030282] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 02/25/2023] [Indexed: 06/18/2023]
Abstract
Melatonin is the hormone that focuses the attention of the researchers in the medical, pharmaceutical, materials, and membranes fields due to its multiple biomedical implications. The variety of techniques and methods for the controlled release of melatonin is linked to the multitude of applications, among which sports medicine occupies a special place. This paper presents the preparation and characterization of composite membranes based on chitosan (Chi) and sulfonated ethylene-propylene-diene terpolymer (sEPDM). The membranes were obtained by controlled vacuum evaporation from an 8% sEPDM solution in toluene (w/w), in which chitosan was dispersed in an ultrasonic field (sEPDM:Chi = 1:1, w/w). For the comparative evaluation of the membranes' performances, a melatonin-chitosan-sulfonated ethylene-propylene-diene terpolymer (Mel:Chi:sEPDM = 0.5:0.5:1.0, w/w/w) test membrane was made. The prepared membranes were morphologically and structurally characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), energy-dispersive spectroscopy analysis (EDAX), thermal analysis (TG, DSC), thermal analysis coupled with chromatography and infrared analysis, and contact angle measurements, but also from the point of view of performance in the process of transport and release of melatonin in dedicated environments (aqueous solutions with controlled pH and salinity). The prepared membranes can release melatonin in amounts between 0.4 mg/cm2·per day (sEPDM), 1.6 mg/ cm2·per day (Chi/sEPDM), and 1.25 mg/cm2·per day (Mel/Chi/SEPDM).
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Affiliation(s)
- Florentina Mihaela Păncescu
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Abbas Abdul Kadhim Klaif Rikabi
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
- Al–Mussaib Technical College, Al–Furat Al–Awsat Technical University (ATU), Babylon–Najaf Street, Kufa 54003, Iraq
| | - Ovidiu Cristian Oprea
- Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Alexandra Raluca Grosu
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Aurelia Cristina Nechifor
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Vlad-Alexandru Grosu
- Department of Electronic Technology and Reliability, Faculty of Electronics, Telecommunications and Information Technology, University Politehnica of Bucharest, 061071 Bucharest, Romania
| | - Szidonia-Katalin Tanczos
- Department of Bioengineering, University Sapientia of Miercurea-Ciuc, 500104 Miercurea-Ciuc, Romania
| | - Florina Dumitru
- Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Gheorghe Nechifor
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Simona Gabriela Bungău
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
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21
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Depleted uranium causes renal mitochondrial dysfunction through the ETHE1/Nrf2 pathway. Chem Biol Interact 2023; 372:110356. [PMID: 36681261 DOI: 10.1016/j.cbi.2023.110356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 01/08/2023] [Accepted: 01/18/2023] [Indexed: 01/20/2023]
Abstract
The kidney is the main organ affected by acute depleted uranium (DU) toxicity. The mechanism of nephrotoxicity induced by DU is complex and needs to be further explored. This study aimed to elucidate the function of mitochondrial dysfunction in nephrotoxicity generated by DU and confirm the latent mechanism. We verified that DU (2.5-10 mg/kg) caused mitochondrial dysfunction in male rat kidneys and decreased ATP content and the mitochondrial membrane potential. In addition, melatonin (20 mg/kg), as an antioxidant, alleviated DU-induced oxidative stress and mitochondrial dysfunction in male rats, further reducing kidney damage caused by DU. These results indicate that mitochondrial dysfunction plays a vital role in DU nephrotoxicity. When ethylmalonic encephalopathy 1 (ETHE1) was knocked down, DU-induced oxidative stress and mitochondrial dysfunction were increased, and renal injury was aggravated. When exogenous ETHE1 protein was applied to renal cells, the opposite changes were observed. We also found that ETHE1 knockdown increased the expression of NF-E2-related factor 2 (Nrf2), a vital oxidative stress regulator, and its downstream molecules heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). Nrf2 knockout also aggravated DU-induced oxidative stress, mitochondrial dysfunction, and kidney damage. In conclusion, DU causes oxidative stress and antioxidant defense imbalance in renal cells through the ETHE1/Nrf2 pathway, further causing mitochondrial dysfunction and ultimately leading to nephrotoxicity.
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22
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Taner N, Haskologlu IC, Erdag E, Mercan M, Chuckwunyere U, Ulker D, Sehirli AO, Abacioglu N. Chronobiological Efficacy of Combined Therapy of Pelargonium Sidoides and Melatonin in Acute and Persistent Cases of COVID-19: A Hypothetical Approach. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1412:427-442. [PMID: 37378781 DOI: 10.1007/978-3-031-28012-2_23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
Since the outbreak of the first SARS-CoV-2 epidemic in China, pharmacists have rapidly engaged and developed strategies for pharmaceutical care and supply. According to the guidelines of the International Pharmaceutical Federation (FIP), clinical pharmacists/hospital pharmacists, as members of care teams, play one of the most important roles in the pharmaceutical care of patients with COVID-19. During this pandemic, many immuno-enhancing adjuvant agents have become critical in addition to antivirals and vaccines in order to overcome the disease more easily. The liquid extract obtained from the Pelargonium sidoides plant is used for many indications such as colds, coughs, upper respiratory tract infections, sore throat, and acute bronchitis. The extract obtained from the roots of the plant has been observed to have antiviral and immunomodulatory activity. In addition to its anti-inflammatory and antioxidant effects, melatonin plays a role in suppressing the cytokine storm that can develop during COVID-19 infection. Knowing that the severity and duration of COVID-19 symptoms vary within 24 hours and/or in different time periods indicates that COVID-19 requires a chronotherapeutic approach. Our goal in the management of acute and long COVID is to synchronize the medication regimen with the patient's biological rhythm. This chapter provides a comprehensive review of the existing and emerging literature on the chronobiological use of Pelargonium sidoides and melatonin during acute and prolonged COVID-19 episodes.
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Affiliation(s)
- Neda Taner
- Istanbul Medipol University, School of Pharmacy, Department of Clinical Pharmacy, Istanbul, Turkey
| | - Ismail Celil Haskologlu
- Near East University, Faculty of Pharmacy, Department of Pharmacology, Nicosia, Mersin 10, Turkey
| | - Emine Erdag
- Near East University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Nicosia, Mersin 10, Turkey
| | - Merve Mercan
- Near East University, Faculty of Pharmacy, Department of Pharmacology, Nicosia, Mersin 10, Turkey
| | - Ugochukwu Chuckwunyere
- Near East University, Faculty of Pharmacy, Department of Pharmacology, Nicosia, Mersin 10, Turkey
| | - Damla Ulker
- Near East University, Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Nicosia, Mersin 10, Turkey
| | - Ahmet Ozer Sehirli
- Near East University, Faculty of Dentistry, Department of Pharmacology, Nicosia, Mersin 10, Turkey
| | - Nurettin Abacioglu
- Near East University, Faculty of Pharmacy, Department of Pharmacology, Nicosia, Mersin 10, Turkey
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23
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Dholariya S, Singh RD, Patel KA. Melatonin: Emerging Player in the Management of Oral Cancer. Crit Rev Oncog 2023; 28:77-92. [PMID: 37830217 DOI: 10.1615/critrevoncog.2023048934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
Oral cancer (OC) has emerged as a major medical and social issue in many industrialized nations due to the high death rate. It is becoming increasingly common in people under the age of 45, although the underlying causes and mechanisms of this increase remain unclear. Melatonin, as a pleiotropic hormone, plays a pivotal role in a wide variety of cellular and physiological functions. Mounting evidence supports melatonin's ability to modify/influence oral carcinogenesis, help in the reduction of the incidence of OC, and increase chemo- and radiosensitivity. Despite its potential anti-carcinogenic effects, the precise function of melatonin in the management of OC is not well understood. This review summarizes the current knowledge regarding melatonin function in anti-carcinogenesis mechanisms for OC. In addition, clinical assessment and the potential therapeutic utility of melatonin in OC are discussed. This review will provide a basis for researchers to create new melatonin-based personalized medicines for treating and preventing OC.
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Affiliation(s)
- Sagar Dholariya
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Rajkot, Gujarat, India
| | - Ragini D Singh
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Rajkot, Gujarat, India
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24
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Sevastre-Berghian AC, Casandra C, Gheban D, Olteanu D, Olanescu Vaida Voevod MC, Rogojan L, Filip GA, Bâldea I. Neurotoxicity of Bisphenol A and the Impact of Melatonin Administration on Oxidative Stress, ERK/NF-kB Signaling Pathway, and Behavior in Rats. Neurotox Res 2022; 40:1882-1894. [PMID: 36515867 DOI: 10.1007/s12640-022-00618-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/25/2022] [Accepted: 12/05/2022] [Indexed: 12/15/2022]
Abstract
Bisphenol A (BPA) exposure can be associated with neurodevelopmental disorders due to impairment of cell proliferation and synaptic development. Our study evaluated the effects of melatonin (MEL) on ambulatory activity, lipid peroxidation, cytokines, ERK/NF-kB signaling pathway in the hippocampus and frontal lobe, and histopathological changes in the hippocampus of the BPA-treated rats. The animals were divided into 4 groups: control, BPA, BPA + MEL I, and BPA + MEL II. MEL I (20 mg/kg b.w.) and MEL II (40 mg/kg b.w.) were orally administered for 28 days. On the 29th day, BPA (1 mg/kg b.w.) was intraperitoneally administered, and, after 24 h, an open field test (OFT) and an elevated plus maze (EPM) were conducted. The results showed that the MEL II group made significantly more entries in the open arms of EPM, traveled significantly greater distance, and spent more time in the central part of OFT. Malondialdehyde levels were diminished by MEL II in the hippocampus and by MEL I in the frontal lobe. In the hippocampus, the MAPK level was significantly lowered by both doses of MEL (p < 0.05) while in the frontal lobe, only MEL II reduced the MAPK activation. MEL I and II significantly decreased the γH2AX and upregulated the NFkB and pNFkB expressions in the hippocampus while MEL II downregulated the MCP1 expression. Both doses of MEL attenuated the BPA-evoked histopathological alterations in the hippocampus. These data indicate that MEL can mediate the neuroprotection against BPA-induced neurotoxicity and improves behavioral changes suggesting a real potential as a protective agent in brain toxicity.
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Affiliation(s)
- Alexandra C Sevastre-Berghian
- Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006, Cluj-Napoca-Napoca, Romania
| | - Cristina Casandra
- Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006, Cluj-Napoca-Napoca, Romania
| | - Dan Gheban
- Department of Morphopathology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 3-5 Clinicilor Street, 400006, Cluj-Napoca-Napoca, Romania
| | - Diana Olteanu
- Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006, Cluj-Napoca-Napoca, Romania
| | | | - Liliana Rogojan
- Department of Morphopathology, District Hospital, 3-5 Clinicilor Street, 400006, Cluj-Napoca Napoca, Romania
| | - Gabriela A Filip
- Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006, Cluj-Napoca-Napoca, Romania.
| | - Ioana Bâldea
- Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006, Cluj-Napoca-Napoca, Romania
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25
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Yuan B, Liu G, Dai Z, Wang L, Lin B, Zhang J. CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers. Cancers (Basel) 2022; 14:cancers14225641. [PMID: 36428734 PMCID: PMC9688555 DOI: 10.3390/cancers14225641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/15/2022] [Accepted: 11/16/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1) is a critical metabolic enzyme of melatonin. Although melatonin has been identified to exhibit tumor suppressing activity, the role and mechanism of the clinical and immunological characteristics of CYP1B1 in cancer remain unclear. METHODS In this study, RNA expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) across 33 solid tumors. The expression, survival, immune subtype, molecular subtype, tumor mutation burden (TMB), microsatellite instability (MSI), biological pathways, and function in vitro and vivo were evaluated. The predictive value of CYP1B1 in immune cohorts was further explored. RESULTS We found the dysregulated expression of CYP1B1 was associated with the clinical stage and tumor grade. Immunological correlation analysis showed CYP1B1 was positively correlated with the infiltration of lymphocyte, immunomodulator, chemokine, receptor, and cancer-associated fibroblasts (CAFs) in most cancer. Meanwhile, CYP1B1 was involved in immune subtype and molecular subtype, and was connected with TMB, MSI, neoantigen, the activation of multiple melatonergic and immune-related pathways, and therapeutic resistance. CONCLUSIONS Together, this study comprehensively revealed the role and mechanism of CYP1B1 and explored the significant association between CYP1B1 expression and immune activity. These findings provide a promising predictor and molecular target for clinical immune treatment.
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Affiliation(s)
- Benchao Yuan
- Department of Oncology and Hematology, The Sixth People’s Hospital of Huizhou City, Huiyang Hospital Affiliated to Southern Medical University, Huizhou 516003, China
| | - Guihong Liu
- Department of Radiation Oncology, Dongguan Tungwah Hospital, Dongguan 523120, China
| | - Zili Dai
- Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou 510095, China
| | - Li Wang
- Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou 510095, China
| | - Baisheng Lin
- Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou 510095, China
| | - Jian Zhang
- Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou 510095, China
- Guangzhou Medical University, Guangzhou 511495, China
- Correspondence: ; Tel./Fax: +86-020-66673666
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26
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Sutton SS, Magagnoli J, Cummings TH, Hardin JW. Melatonin as an Antimicrobial Adjuvant and Anti-Inflammatory for the Management of Recurrent Clostridioides difficile Infection. Antibiotics (Basel) 2022; 11:1472. [PMID: 36358127 PMCID: PMC9687053 DOI: 10.3390/antibiotics11111472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/19/2022] [Accepted: 10/20/2022] [Indexed: 09/06/2024] Open
Abstract
Background:Clostridioides difficile (C. difficile) infection (CDI) is strongly associated with inflammation and has the potential to cause recurrent infections. Pre-clinical data suggest that melatonin has beneficial effects in the gastrointestinal tract due to its anti-inflammatory and antibacterial properties. This analysis examines the association between melatonin and the risk of recurrent CDI. Methods: A retrospective cohort study was conducted among patients with an inpatient diagnosis of CDI along with a positive C. difficile polymerase chain reaction (PCR) or enzyme immunoassay (EIA) test result. Patients were followed until the first study end point (death) or the first instance of recurrent infection. Propensity-score weighting was utilized accounting for confounding factors and weighted Cox models were estimated. Results: A total of 24,782 patients met the inclusion criteria, consisting of 3457 patients exposed to melatonin and 21,325 patients with no melatonin exposure. The results demonstrate that those exposed to melatonin were associated with a 21.6% lower risk of recurrent CDI compared to patients without melatonin exposure (HR = 0.784; 95% CI = 0.674-0.912). Conclusion: Our results demonstrate a decreased rate of recurrent CDI in patients exposed to melatonin. Further research on melatonin as an antimicrobial adjuvant and anti-inflammatory is warranted for the management of recurrent CDI.
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Affiliation(s)
- S. Scott Sutton
- Dorn Research Institute, Columbia Veterans Affairs Health Care System, Columbia, SC 29209, USA
- Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
| | - Joseph Magagnoli
- Dorn Research Institute, Columbia Veterans Affairs Health Care System, Columbia, SC 29209, USA
- Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
| | - Tammy H. Cummings
- Dorn Research Institute, Columbia Veterans Affairs Health Care System, Columbia, SC 29209, USA
- Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
| | - James W. Hardin
- Dorn Research Institute, Columbia Veterans Affairs Health Care System, Columbia, SC 29209, USA
- Department of Epidemiology & Biostatistics, University of South Carolina, Columbia, SC 29208, USA
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27
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Yang K, Qiu X, Cao L, Qiu S. The role of melatonin in the development of postmenopausal osteoporosis. Front Pharmacol 2022; 13:975181. [PMID: 36278157 PMCID: PMC9585202 DOI: 10.3389/fphar.2022.975181] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 09/26/2022] [Indexed: 11/28/2022] Open
Abstract
Melatonin is an important endogenous hormone that modulates homeostasis in the microenvironment. Recent studies have indicated that serum melatonin levels are closely associated with the occurrence and development of osteoporosis in postmenopausal women. Exogenous melatonin could also improve bone mass and increase skeletal strength. To determine the underlying mechanisms of melatonin in the prevention and treatment of postmenopausal osteoporosis, we performed this review to analyze the role of melatonin in bone metabolism according to its physiological functions. Serum melatonin is related to bone mass, the measurement of which is a potential method for the diagnosis of osteoporosis. Melatonin has a direct effect on bone remodeling by promoting osteogenesis and suppressing osteoclastogenesis. Melatonin also regulates the biological rhythm of bone tissue, which benefits its osteogenic effect. Additionally, melatonin participates in the modulation of the bone microenvironment. Melatonin attenuates the damage induced by oxidative stress and inflammation on osteoblasts and prevents osteolysis from reactive oxygen species and inflammatory factors. As an alternative drug for osteoporosis, melatonin can improve the gut ecology, remodel microbiota composition, regulate substance absorption and maintain metabolic balance, all of which are beneficial to the health of bone structure. In conclusion, our review systematically demonstrates the effects of melatonin on bone metabolism. Based on the evidence in this review, melatonin will play a more important role in the diagnosis, prevention and treatment of postmenopausal osteoporosis.
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Affiliation(s)
- Keda Yang
- Department of Orthopedics, First Hospital of China Medical University, Shenyang, China
| | - Xueshan Qiu
- Department of Pathology, The First Affiliated Hospital of China Medical University and College of Basic Medical Sciences Shenyang, Shenyang, Liaoning, China
| | - Lili Cao
- Department of Medical Oncology, First Hospital of China Medical University, Shenyang, China
- *Correspondence: Lili Cao, ; Shui Qiu,
| | - Shui Qiu
- Department of Orthopedics, First Hospital of China Medical University, Shenyang, China
- *Correspondence: Lili Cao, ; Shui Qiu,
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28
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Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients 2022; 14:3934. [PMID: 36235587 PMCID: PMC9571539 DOI: 10.3390/nu14193934] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/20/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer's disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a "sunlight deficiency" and reduced melatonin secretion as a result of "darkness deficiency" from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin's mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.
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Affiliation(s)
- Deanna M. Minich
- Department of Human Nutrition and Functional Medicine, University of Western States, Portland, OR 97213, USA
| | - Melanie Henning
- Department of Sports and Performance Psychology, University of the Rockies, Denver, CO 80202, USA
| | - Catherine Darley
- College of Naturopathic Medicine, National University of Natural Medicine, Portland, OR 97201, USA
| | - Mona Fahoum
- School of Naturopathic Medicine, Bastyr University, Kenmore, WA 98028, USA
| | - Corey B. Schuler
- School of Nutrition, Sonoran University of Health Sciences, Tempe, AZ 85282, USA
- Department of Online Education, Northeast College of Health Sciences, Seneca Falls, NY 13148, USA
| | - James Frame
- Natural Health International Pty., Ltd., Sydney, NSW 2000, Australia
- Symphony Natural Health, Inc., West Valley City, UT 84119, USA
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29
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Ma W, Wu H, Li G, Yan L, Wang L, Zhao M, Guan S, Xu S, Guo X, Liu F, Ji P, Wusiman A, Liu G. Melatonin promotes the growth and development of lambs by increasing growth hormone and testosterone, targeting on apoptosis signaling pathway and intestinal microflora. Front Endocrinol (Lausanne) 2022; 13:966120. [PMID: 36060949 PMCID: PMC9439620 DOI: 10.3389/fendo.2022.966120] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/25/2022] [Indexed: 11/23/2022] Open
Abstract
Melatonin is an indole-like neuroendocrine hormone. A large number of studies have shown that melatonin can improve production performance of ewes, but it is not clear in lambs. In this study, the growth and development of the 2-month-old lambs implanted with melatonin were monitored for 60 days. The results showed that the growth rate of body weight and body skew length of lambs with melatonin treatment were significantly improved compared to the controls. The similar results were also observed in red blood cell count, hematocrit, red blood cell volume distribution width, the levels of growth hormone, testosterone, immunoglobulin A, immunoglobulin M and albumin. In addition, the cross sectional area of muscle fibers and adipose cells of lambs with melatonin implantation were also significantly increased compared to the controls (P<0.05). To further explore the potential mechanisms, the muscle and adipose tissue were selected for transcriptome sequencing. KEGG enrichment results showed that melatonin regulated the expression of genes related to apoptotic signaling pathway in muscle and adipocytes. Since the intestinal microbiota are involved in the nutritional balance and animal growth, the 16SrRNA sequencing related to the intestinal microbiota was also performed. The data indicated that the structural differences of fecal microflora mainly occur in the pathways of Cardiovascular disease, Excretory system and Signaling molecules and interaction. In brief, melatonin promotes the growth and development of lambs. The potential mechanisms may be that melatonin increased the growth hormone and testosterone mediated apoptosis signaling pathway and regulated intestinal microbial flora. Our results provide valuable information for melatonin to improve the production of sheep husbandry in the future.
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Affiliation(s)
- Wenkui Ma
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Hao Wu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Guangdong Li
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Laiqing Yan
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Likai Wang
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Mengmeng Zhao
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shengyu Guan
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shang Xu
- Inner Mongolia Golden Grassland Ecological Technology Group Co., LTD., Inner Mongolia, China
| | - Xiaokai Guo
- Inner Mongolia Golden Grassland Ecological Technology Group Co., LTD., Inner Mongolia, China
| | - Fenze Liu
- Inner Mongolia Golden Grassland Ecological Technology Group Co., LTD., Inner Mongolia, China
| | - Pengyun Ji
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Abulizi Wusiman
- College of Animal Science, Xinjiang Agricultural University, Urumqi, China
| | - Guoshi Liu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China
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