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1
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Zhang S, Dong H, Jin X, Sun J, Li Y. The multifaceted roles of macrophages in the transition from hepatitis to hepatocellular carcinoma: From mechanisms to therapeutic strategies. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167676. [PMID: 39828046 DOI: 10.1016/j.bbadis.2025.167676] [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: 11/28/2024] [Revised: 01/06/2025] [Accepted: 01/15/2025] [Indexed: 01/22/2025]
Abstract
Macrophages are central to the progression from hepatitis to hepatocellular carcinoma (HCC), with their remarkable plasticity and ability to adapt to the changing liver microenvironment. Chronic inflammation, fibrosis, and ultimately tumorigenesis are driven by macrophage activation, making them key regulators of liver disease progression. This review explores the diverse roles of macrophages in the transition from hepatitis to HCC. In the early stages of hepatitis, macrophages are essential for pathogen clearance and tissue repair. However, chronic activation leads to prolonged inflammation, which exacerbates liver damage and promotes fibrosis. As the disease progresses to liver fibrosis, macrophages interact with hepatic stellate cells, fostering a pro-tumorigenic microenvironment that supports HCC development. In hepatocarcinogenesis, macrophages contribute to tumor initiation, growth, metastasis, immune evasion, cancer stem cell maintenance, and angiogenesis. Their functional plasticity enables them to adapt to the tumor microenvironment, thereby promoting tumor progression and resistance to therapy. Targeting macrophages represents a promising strategy for preventing and treating HCC. Therapeutic approaches, including reprogramming macrophage phenotypes to enhance anti-tumor immunity, blocking macrophage recruitment and activation, and utilizing nanoparticle-based drug delivery systems, may provide new avenues for combating HCC by modulating macrophage functions and tumor microenvironment dynamics.
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Affiliation(s)
- Shuairan Zhang
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, PR China
| | - Hang Dong
- Phase I Clinical Trials Center, The People's Hospital of China Medical University, Shenyang, PR China
| | - Xiuli Jin
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, PR China
| | - Jing Sun
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, PR China
| | - Yiling Li
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, PR China.
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2
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Elhrech H, Aguerd O, El Kourchi C, Gallo M, Naviglio D, Chamkhi I, Bouyahya A. Comprehensive Review of Olea europaea: A Holistic Exploration into Its Botanical Marvels, Phytochemical Riches, Therapeutic Potentials, and Safety Profile. Biomolecules 2024; 14:722. [PMID: 38927125 PMCID: PMC11201932 DOI: 10.3390/biom14060722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Human health is now inextricably linked to lifestyle choices, which can either protect or predispose people to serious illnesses. The Mediterranean diet, characterized by the consumption of various medicinal plants and their byproducts, plays a significant role in protecting against ailments such as oxidative stress, cancer, and diabetes. To uncover the secrets of this natural treasure, this review seeks to consolidate diverse data concerning the pharmacology, toxicology, phytochemistry, and botany of Olea europaea L. (O. europaea). Its aim is to explore the potential therapeutic applications and propose avenues for future research. Through web literature searches (using Google Scholar, PubMed, Web of Science, and Scopus), all information currently available on O. europaea was acquired. Worldwide, ethnomedical usage of O. europaea has been reported, indicating its effectiveness in treating a range of illnesses. Phytochemical studies have identified a range of compounds, including flavanones, iridoids, secoiridoids, flavonoids, triterpenes, biophenols, benzoic acid derivatives, among others. These components exhibit diverse pharmacological activities both in vitro and in vivo, such as antidiabetic, antibacterial, antifungal, antioxidant, anticancer, and wound-healing properties. O. europaea serves as a valuable source of conventional medicine for treating various conditions. The findings from pharmacological and phytochemical investigations presented in this review enhance our understanding of its therapeutic potential and support its potential future use in modern medicine.
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Affiliation(s)
- Hamza Elhrech
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco; (H.E.); (O.A.)
| | - Oumayma Aguerd
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco; (H.E.); (O.A.)
| | - Chaimae El Kourchi
- Laboratory of Materials, Nanotechnology and Environment, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco;
| | - Monica Gallo
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy
| | - Daniele Naviglio
- Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 4, 80126 Naples, Italy;
| | - Imane Chamkhi
- Geo-Biodiversity and Natural Patrimony Laboratory (GeoBio), Geophysics, Natural Patrimony, Research Center (GEOPAC), Scientific Institute, Mohammed V University in Rabat, Rabat 10106, Morocco;
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco; (H.E.); (O.A.)
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3
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Riccio AV, Costa BK, Alonso MA, Affonso FJ, França DS, Nichi M, Belli CB, McLean AK, Boakari YL, Fernandes CB. Comparative Assessment of Oxidative and Antioxidant Parameters in Mule and Horse Neonates during Their First Month of Extrauterine Adaptation. Animals (Basel) 2023; 13:3878. [PMID: 38136914 PMCID: PMC10741120 DOI: 10.3390/ani13243878] [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: 11/01/2023] [Revised: 11/29/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
After parturition, a rapid transition occurs from the intrauterine to the extrauterine milieu, exposing neonates to physiological circumstances characterized by oxidative conditions that instigate the generation of reactive oxygen species. These free radicals play pivotal roles in physiological processes; however, an imbalance between their production and the removal of antioxidants can result in severe cellular damage. The main objective of this study was to compare the oxidative and antioxidant profiles in mule and horse neonates immediately post-parturition, as well as at subsequent time points (1, 6, 12, and 24 h, 7 and 30 days) during their extrauterine existence. The parameters assessed included the systemic concentrations of Thiobarbituric Acid Reactive Substances (TBARS) and carbonyl groups; the activities of the antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx); and the levels of the total, indirect, and direct bilirubin. Our results showed no interaction effect between the neonatal groups and the assessed time points for the variables under investigation. Notably, the concentrations of TBARS, as a marker of lipid peroxidation, and bilirubin were consistently lower in the mules, whereas the glutathione peroxidase (GPx) activity exhibited higher levels in this group. The bilirubin levels were notably reduced in the mule neonates. The TBARS demonstrated a progressive decrease over the observation period in both groups, while the GPx activity remained relatively stable from birth to 7 days, with a substantial increase evident at the 30-day mark. Protein oxidation was not affected by the group and time, while for the SOD values, all times were statistically similar, except for the lower activity at T1h. Consequently, our findings lead us to the conclusion that neonatal mules and horses manifest distinct patterns of oxidative activity and antioxidant capacity during the initial month of their extrauterine existence, potentially indicative of different adaptation mechanisms to the extrauterine environment.
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Affiliation(s)
- Amanda Vallone Riccio
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil; (A.V.R.); (B.K.C.); (M.A.A.); (F.J.A.); (D.S.F.); (M.N.)
| | - Barbara Kolecha Costa
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil; (A.V.R.); (B.K.C.); (M.A.A.); (F.J.A.); (D.S.F.); (M.N.)
| | - Maria Augusta Alonso
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil; (A.V.R.); (B.K.C.); (M.A.A.); (F.J.A.); (D.S.F.); (M.N.)
| | - Fernanda Jordão Affonso
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil; (A.V.R.); (B.K.C.); (M.A.A.); (F.J.A.); (D.S.F.); (M.N.)
| | - Danilo Souza França
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil; (A.V.R.); (B.K.C.); (M.A.A.); (F.J.A.); (D.S.F.); (M.N.)
| | - Marcilio Nichi
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil; (A.V.R.); (B.K.C.); (M.A.A.); (F.J.A.); (D.S.F.); (M.N.)
| | - Carla Bargi Belli
- Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil;
| | - Amy Katherine McLean
- Department of Animal Science, University of California Davis, Davis, CA 95616, USA;
| | - Yatta Linhares Boakari
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Claudia Barbosa Fernandes
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil; (A.V.R.); (B.K.C.); (M.A.A.); (F.J.A.); (D.S.F.); (M.N.)
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Dewenter I, Kumbrink J, Poxleitner P, Smolka W, Liokatis P, Fliefel R, Otto S, Obermeier KT. New insights into redox-related risk factors and therapeutic targets in oral squamous cell carcinoma. Oral Oncol 2023; 147:106573. [PMID: 37951115 DOI: 10.1016/j.oraloncology.2023.106573] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 09/13/2023] [Accepted: 09/18/2023] [Indexed: 11/13/2023]
Abstract
Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral cavity accounting for 90 % of oral cancer with a global incidence of 350.000 new cases per year. Curative resection along with adjuvant radiation therapy or a combination of radiotherapy with chemotherapy remain as gold standard in treating OSCC. Still, local recurrence, lymph nodal recurrence, and complications of radiation remain the main cause of tumor-related mortality. Reactive oxygen species are not only correlated to the etiology of OSCC due to oxidative DNA damage, lipid peroxidation or effecting signal transduction cascades that effect cell proliferation and tumorigenesis, but are also of great interest in the therapy of OSCC patients. As induced oxidative stress can be used therapeutically for the induction of tumor cell death, redox targets might be a therapeutic addition to the conventional treatment options. In this review, we discuss markers of impaired redox homeostasis as well as potential redox-related treatment targets in OSCC.
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Affiliation(s)
- Ina Dewenter
- Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilians University, 80337 Munich, Germany.
| | - Joerg Kumbrink
- Institute of Pathology, Faculty of Medicine, Ludwig Maximilians University, Munich, Germany
| | - Philipp Poxleitner
- Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilians University, 80337 Munich, Germany
| | - Wenko Smolka
- Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilians University, 80337 Munich, Germany
| | - Paris Liokatis
- Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilians University, 80337 Munich, Germany
| | - Riham Fliefel
- Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilians University, 80337 Munich, Germany
| | - Sven Otto
- Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilians University, 80337 Munich, Germany
| | - Katharina Theresa Obermeier
- Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, Ludwig Maximilians University, 80337 Munich, Germany
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Meibers HE, Warrick KA, VonHandorf A, Vallez CN, Kawarizadeh K, Saha I, Donmez O, Jain VG, Kottyan LC, Weirauch MT, Pasare C. Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells. Cell Rep 2023; 42:113180. [PMID: 37794597 PMCID: PMC10654673 DOI: 10.1016/j.celrep.2023.113180] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 08/09/2023] [Accepted: 09/12/2023] [Indexed: 10/06/2023] Open
Abstract
Cognate interaction between CD4+ effector memory T (TEM) cells and dendritic cells (DCs) induces innate inflammatory cytokine production, resulting in detrimental autoimmune pathology and cytokine storms. While TEM cells use tumor necrosis factor (TNF) superfamily ligands to activate DCs, whether TEM cells prompt other DC-intrinsic changes that influence the innate inflammatory response has never been investigated. We report the surprising discovery that TEM cells trigger double-strand DNA breaks via mitochondrial reactive oxygen species (ROS) production in interacting DCs. Initiation of the DNA damage response in DCs induces activation of a cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS)-independent, non-canonical stimulator of interferon genes (STING)-TNF receptor-associated factor 6 (TRAF6)-nuclear factor κB (NF-κB) signaling axis. Consequently, STING-deficient DCs display reduced NF-κB activation and subsequent defects in transcriptional induction and functional production of interleukin-1β (IL-1β) and IL-6 following their interaction with TEM cells. The discovery of TEM cell-induced innate inflammation through DNA damage and a non-canonical STING-NF-κB pathway presents this pathway as a potential target to alleviate T cell-driven inflammation in autoimmunity and cytokine storms.
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Affiliation(s)
- Hannah E Meibers
- Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Kathrynne A Warrick
- Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Andrew VonHandorf
- Center for Autoimmune Genetics and Etiology and Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Charles N Vallez
- Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Kiana Kawarizadeh
- Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Irene Saha
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Omer Donmez
- Center for Autoimmune Genetics and Etiology and Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Viral G Jain
- Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Leah C Kottyan
- Center for Autoimmune Genetics and Etiology and Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA
| | - Matthew T Weirauch
- Center for Autoimmune Genetics and Etiology and Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA
| | - Chandrashekhar Pasare
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA.
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6
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Dincel GC, Yavuz O, Yildirim S, Al-Olayan EM, El-Ashram S. ADAMTS-13 and HMGB1-induced oxidative stress in Taenia multiceps-infected animals. Sci Rep 2023; 13:17929. [PMID: 37863934 PMCID: PMC10589341 DOI: 10.1038/s41598-023-44376-0] [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: 04/05/2023] [Accepted: 10/07/2023] [Indexed: 10/22/2023] Open
Abstract
This study investigated the cytotoxic effects of oxidative stress (OS), high mobility group box 1 (HMGB1), ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs), and neuropathology associated with coenurus cerebralis (Taenia multiceps). ADAMTS-13, HMGB1, glutathione reductase (GR), copper/zinc superoxide dismutase (Cu/Zn SOD), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression levels were studied. The study found that ADAMTS-13 (P < 0.005), HMGB1 (P < 0.005), GR (P < 0.005), Cu/Zn SOD (P < 0.005), and 8-OHdG (P < 0.005) levels were significantly higher in T. multiceps (c. cerebralis)-infected animals compared to healthy control animals. This study's most important finding was that HMGB1 up-regulation in neurons, endothelial cells, and glial cells can directly cause brain parenchymal destruction and that HMGB1-mediated oxidative stress plays a crucial role in the neuropathogenesis of coenurosis. The results also showed that increased levels of ADAMTS-13 may play a pivotal role in regulating and protecting the blood-brain barrier integrity and neuroprotection. These findings also suggest that ADAMTS-13 and HMGB1 compete in the prevention or formation of microthrombi, which was regarded as a remarkable finding. ADAMTS-13 and HMGB1 are valuable biomarkers for disease risk assessment, estimating host neuropathy following T. multiceps (c. cerebralis) exposure, and providing a new therapeutic target. This is the first study to show that HMGB1 and ADAMTS-13 are expressed in reactive cells and are associated with neuroimmunopathology in coenurosis.
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Affiliation(s)
- Gungor Cagdas Dincel
- Eskil Vocational School, Laboratory and Veterinary Science, Aksaray University, Aksaray, Turkey.
| | - Orhan Yavuz
- Department of Pathology, Faculty of Veterinary Medicine, Aksaray University, Aksaray, Turkey
| | - Serkan Yildirim
- Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Ebtesam M Al-Olayan
- Department of Zoology, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Saeed El-Ashram
- Zoology Department, Faculty of Science, Kafrelsheikh University, Kafr El-Sheikh, 33516, Egypt.
- College of Life Science and Engineering, Foshan University, 18 Jiangwan Street, Foshan, 528231, Guangdong Province, China.
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Recent Advances, Systemic Therapy, and Molecular Targets in Adenoid Cystic Carcinoma of the Head and Neck. J Clin Med 2023; 12:jcm12041463. [PMID: 36835997 PMCID: PMC9967509 DOI: 10.3390/jcm12041463] [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: 01/08/2023] [Revised: 02/03/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023] Open
Abstract
With an incidence of 3-4.5 cases per million, adenoid cystic carcinoma (ACC) of the head and neck is one of the most common tumors of the parotid and sublingual salivary glands. In the clinical course, ACC is shown to have an aggressive long-term behavior, which leads to the fact that radical surgical resection of the tumor with tumor-free margins remains the "gold standard" in treating ACC. Particle radiation therapy and systemic molecular biological approaches offer new treatment options. However, risk factors for the formation and prognosis of ACC have not yet been clearly identified. The aim of the present review was to investigate long-term experience of diagnosis and treatment as well as risk and prognostic factors for occurrence and outcome of ACC.
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Tsukahara T, Makioka-Itaya Y, Takimoto H, Ijichi T. Oral supplementation of a cell preparation of Enterococcus faecalis strain EC-12 stimulates superoxide dismutase production in the livers of healthy and arthritis-induced mice. J Clin Biochem Nutr 2023; 72:39-45. [PMID: 36777079 PMCID: PMC9899913 DOI: 10.3164/jcbn.22-77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/03/2022] [Indexed: 11/07/2022] Open
Abstract
Hepatitis, a major human chronic inflammation disease, has been linked to oxidative stress, which can be initiated by radicals produced during the oxidative metabolism. Oxidative damage has been also observed in arthritis-induced mice. Here we evaluated whether supplementation of a cell preparation of Enterococcus faecalis EC-12 could induce superoxide dismutase activity and/or damage in the livers of healthy mice or mice with arthritis. In Experiment 1, both healthy and arthritis-induced mice were orally given a saline solution, or a solution with a low (0.2 mg/mouse/day) or a high (2.0 mg/mouse/day) concentration of E. faecalis EC-12 for 49 consecutive days. Manganese superoxide dismutase activity increased in E. faecalis EC-12-supplemented mice but with no arthritis. In Experiment 2, mice received orally either a saline or an E. faecalis EC-12 suspension (10 mg/kg of body weight/day) for 28 consecutive days. No changes in tissues and levels of function markers and 8-hydroxy-2'-deoxyguanosine were observed in mouse livers, inferring that E. faecalis EC-12 supplementation caused no damage. While mRNA expression of copper/zinc superoxide dismutase remained unaltered, that of manganese superoxide dismutase increased in E. faecalis EC-12 administration mice. In conclusion, at least in healthy mice, E. faecalis EC-12 supplementation stimulated manganese superoxide dismutase activity in liver tissues with no side effects.
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Affiliation(s)
- Takamitsu Tsukahara
- Kyoto Institute of Nutrition & Pathology, 7-2 Furuikedani Tachikawa, Ujitawara, Kyoto 610-0231, Japan,To whom correspondence should be addressed. E-mail:
| | - Yuko Makioka-Itaya
- Life Science Division, Combi Corporation, Nishibori, Sakura-ku, Saitama 338-0832, Japan
| | - Hiroaki Takimoto
- Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
| | - Tetsuo Ijichi
- Life Science Division, Combi Corporation, Nishibori, Sakura-ku, Saitama 338-0832, Japan
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Novel nitrogen mustard-artemisinin hybrids with potent anti-leukemia action through DNA damage and activation of GPx. Eur J Med Chem 2022; 244:114783. [DOI: 10.1016/j.ejmech.2022.114783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 09/12/2022] [Accepted: 09/15/2022] [Indexed: 11/22/2022]
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10
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Hernandez-Haro N, Solis-Calero C, Casasnovas R, Morell C, Grand A, Frau J, Ortega-Castro J. Formation Mechanism of Inter-Crosslink in DNA by Nitrogen Oxides Pollutants through A Diazonium Intermediate. Int J Mol Sci 2022; 23:10621. [PMID: 36142522 PMCID: PMC9502170 DOI: 10.3390/ijms231810621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 09/06/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Outdoor air pollution is a mixture of multiple atmospheric pollutants, among which nitrogen oxide (NOx) stands out due to its association with several diseases. NOx reactivity can conduct to DNA damage as severe as interstrand crosslinks (ICL) formation, that in turn is able to block DNA replication and transcription. Experimental studies have suggested that the ICL formation due to NOx is realized through a diazonium intermediate (DI). In this work, we have modeled the DI structure, including a DNA double-strand composed of two base pairs GC/CG, being diazotized as one of the guanine nucleotides. The structural stability of DNA with DI lesion was essayed through 500 ns molecular dynamics simulations. It was found that the DNA structure of the oligonucleotide is stable when the DI is present since the loss of a Guanine-Cytosine hydrogen bond is replaced by the presence of two cation-π interactions. Additionally, we have studied the mechanism of formation of a crosslink between the two guanine nucleobases from the modeled DI by carrying out DFT calculations at the M06-L/DNP+ level of theory. Our results show that the mechanism is thermodynamically favored by a strong stabilization of the ICL product, and the process is kinetically viable since its limiting stage is accessible.
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Affiliation(s)
- Noemi Hernandez-Haro
- Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
| | - Christian Solis-Calero
- Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima 15001, Peru
| | - Rodrigo Casasnovas
- Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa), 07020 Palma de Mallorca, Spain
| | - Christophe Morell
- Institut des Sciences Analytiques, Université de Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5280, CEDEX, 69622 Villeurbanne, France
| | - Andre Grand
- Université Grenoble Alpes, CEA, CNRS, INAC-SyMMES, 38000 Grenoble, France
| | - Juan Frau
- Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa), 07020 Palma de Mallorca, Spain
| | - Joaquín Ortega-Castro
- Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa), 07020 Palma de Mallorca, Spain
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11
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Nie X, Wang L. Plant species compositions alleviate toxicological effects of bisphenol A by enhancing growth, antioxidant defense system, and detoxification. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:65755-65770. [PMID: 35501435 DOI: 10.1007/s11356-022-20402-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 04/19/2022] [Indexed: 06/14/2023]
Abstract
Bisphenol A (BPA), a broadly disseminated endocrine disturbing chemicals in environment, is harmful to creatures and plants. Plants can uptake and metabolize BPA, but a single plant species ability is limited. Undeniably, plant species compositions have a more vital ability to remove pollutants than a single plant species. However, the mechanisms of plant species compositions alleviating toxicological effects of bisphenol A are poorly understood. Here, we administered plant species compositions, which based on a full-factorial design of Phragmites australis (A), Typha latifolia (B), and Arundo donax (C), to unveil their role in BPA exposure. The results illustrated that the root activity, biomass, and photosynthetic pigment contents of the mixed hydroponic group (e.g., sp(ABC)) were significantly increased under concentration of BPA(1.5, 5, and 10 mg L-1), which showed that the root activity, fresh weight, dry weight, chlorophyll a, and total chlorophyll contents of shoots were increased. While mixed-hydroponic culture groups (e.g., sp(AB), sp(ABC)) significantly increased antioxidant enzyme activity and antioxidant substances under concentration of BPA(5 and 10 mg L-1), it astoundingly diminished responsive oxygen species (ROS) and malondialdehyde (MDA) substance, proposing that mixed-hydroponic culture groups calmed oxidative stress. Further analysis revealed that mixed-hydroponic culture groups (e.g., sp(AB), sp(AC), sp(ABC)) of 1.5, 5, and 10 mg L-1 BPA exposure significantly increased detoxification enzyme activity of NADPH-cytochrome P450 reductase (CPR), glutathione S-transferase (GST), and glycosyltransferase (GT). Moreover, mixed-hydroponic culture groups (e.g., sp(AB), sp(AC), sp(ABC)) decreased the BPA substance in leaves, proposing that mixed-hydroponic culture groups advanced BPA metabolism by improving CPR, GST, and GT enzyme activities. These results demonstrated that a mixed-hydroponic culture strategy can alleviate BPA phytotoxicity and possibly offer natural and potential phytoremediation methods for BPA.
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Affiliation(s)
- Xianguang Nie
- College of Environmental Science and Engineering, Ocean University of China, Qingdao, 266100, China
| | - Lin Wang
- College of Environmental Science and Engineering, Ocean University of China, Qingdao, 266100, China.
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12
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Szewczyk-Golec K, Pawłowska M, Wesołowski R, Wróblewski M, Mila-Kierzenkowska C. Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities. Int J Mol Sci 2021; 22:ijms22115705. [PMID: 34071892 PMCID: PMC8198901 DOI: 10.3390/ijms22115705] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/21/2021] [Accepted: 05/25/2021] [Indexed: 12/16/2022] Open
Abstract
Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.
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13
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Effect of N7-methylation on base pairing patterns of guanine: a DFT study. J Mol Model 2021; 27:184. [PMID: 34036469 DOI: 10.1007/s00894-021-04792-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 05/11/2021] [Indexed: 10/21/2022]
Abstract
In this paper, we aim to determine whether the N7-methylation can influence the base pairing properties of guanine by promoting the formation of guanine enol-tautomers. The keto- to -enol-tautomerization of N7-methylguanine (N7mG) and its base pairing patterns with all the canonical DNA bases have been investigated at the M06-2X/6-311+G(d,p) level of density functional theory. The barrier free energy calculations reveal that N7-methylation does not promote the keto- to enol- tautomerization of guanine. The Watson-Crick-like enol-N7mG:T1 or enol-N7mG:T2 base pair similar to what is observed experimentally is found to be energetically more stable than the keto-N7mG:T base pairs. However, the keto-N7mG:C1 which is structurally similar to the canonical G:C base pair is the most stable base pair among all the base pairs studied here. Thus, our calculations predict that N7mG would pair preferably with cytosine during DNA replication but there is also a probability that it can cause mutation through mispairing with thymine, in agreement with experimental observations.
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14
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Vostrikova SM, Grinev AB, Gogvadze VG. Reactive Oxygen Species and Antioxidants in Carcinogenesis and Tumor Therapy. BIOCHEMISTRY (MOSCOW) 2021; 85:1254-1266. [PMID: 33202210 DOI: 10.1134/s0006297920100132] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Strictly regulated balance between the formation and utilization of reactive oxygen species (ROS) is the basis of normal functioning of organisms. ROS play an important role in the regulation of many metabolic processes; however, excessive content of ROS leads to the development of various disorders, including oncological diseases, as a result of ROS-induced mutations in DNA. In tumors, high levels of oxygen radicals promote cell proliferation and metastasis. On the other hand, high content of ROS can trigger cell death, a phenomenon used in the antitumor therapy. Water- and lipid-soluble antioxidants, as well as antioxidant enzyme systems, can inhibit ROS generation; however, they should be used with caution. Antioxidants can suppress ROS-dependent cell proliferation and metastasis, but at the same time, they may inhibit the death of tumor cells if the antitumor therapeutic agents stimulate oxidative stress. The data on the role of antioxidants in the death of tumor cells and on the effects of antioxidants taken as dietary supplements during antitumor therapy, are contradictory. This review focuses on the mechanisms by which antioxidants can affect tumor and healthy cells.
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Affiliation(s)
- S M Vostrikova
- Faculty of Medicine, Lomonosov Moscow State University, Moscow, 119192, Russia.,I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, 119991, Russia
| | - A B Grinev
- I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, 119991, Russia
| | - V G Gogvadze
- Faculty of Medicine, Lomonosov Moscow State University, Moscow, 119192, Russia. .,Division of Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, 171 77, Sweden
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15
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Wang Y, Zhao H, Liu Y, Guo M, Tian Y, Huang P, Xing M. Arsenite induce neurotoxicity of common carp: Involvement of blood brain barrier, apoptosis and autophagy, and subsequently relieved by zinc (Ⅱ) supplementation. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2021; 232:105765. [PMID: 33535132 DOI: 10.1016/j.aquatox.2021.105765] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 12/24/2020] [Accepted: 01/21/2021] [Indexed: 06/12/2023]
Abstract
Arsenic pollution is a common threat to aquatic ecosystems. The effects of chronic exposure to arsenite on the brains of aquatic organisms are unknown. This study was designed to evaluate arsenic-induced brain damage in common carp (Cyprinus carpio) and the ameliorating effects of divalent zinc ion (Zn2+) supplementation from the aspects of oxidative stress (OxS), tight junction (TJ), apoptosis and autophagy. After arsenite exposure (2.83 mg/L) for 30 days, oxidative damage to the brain was determined, as indicated by inhibited antioxidants system (catalase-superoxide dismutase system, and glutathione system) and elevated levels of biomacromolecule peroxidation (malondialdehyde and 8-hydroxydeoxyguanosine). Moreover, we also found functional damage to the brain as suggested by injuries to the blood-brain barrier (decreases in tight junction) and nerve conduction (depletion of AChE). Mechanisticly, apoptotic and autophagic cell death were indicated by typical morphologies including karyopyknosis and autophagosome, accompanying by key bio-indicators (Bcl-2, caspase and autophagy related gene family proteins). In contrast, the coadministration of Zn2+ (1 mg/L) with arsenite effectively alleviated this damage as suggested by the recovery of the aforementioned bioindicators. This study provides new insight into the brain toxicity caused by arsenite and suggests the application of zinc preparations in the aquatic pollution of arsenic.
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Affiliation(s)
- Yu Wang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Hongjing Zhao
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Yachen Liu
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Menghao Guo
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Ye Tian
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China
| | - Puyi Huang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
| | - Mingwei Xing
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
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16
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Curcumin, oxidative stress, and breast cancer. Cancer 2021. [DOI: 10.1016/b978-0-12-819547-5.00032-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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17
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Yao C, Sheng J, Yan S, Tian S, Meng Z, Zhou Z, Zhu W. Enantioselectivity effects of imazethapyr enantiomers to metabolic responses in mice. PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY 2020; 168:104619. [PMID: 32711760 DOI: 10.1016/j.pestbp.2020.104619] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 05/25/2020] [Accepted: 05/25/2020] [Indexed: 06/11/2023]
Abstract
Imazethapyr (IMZT) is a typical chiral pesticide with two enantiomers with the R-IMZT having the main herbicidal activity. However, the enantioselectivity of the effects of IMZT enantiomers on human and animals is still unclear. In this study, a nuclear magnetic resonance (NMR)-based metabolomics method and determination of oxidative stress were used to evaluate the enantioselectivity of IMZT enantiomers in mice. The results showed that the R-IMZT caused larger disturbances of endogenous metabolites and the S-IMZT had stronger interferences to oxidation defense system. The significantly perturbed metabolic pathways in mice exposed to the R-enantiomer were the valine, leucine and isoleucine biosynthesis pathway as well as the phenylalanine, tyrosine and tryptophan biosynthesis pathway. However, exposure of mice to the S-enantiomer did not significantly affect the metabolic pathways, but exposure led to an increase of catalase (CAT) activity and an increase in malondialdehyde (MDA) content in the liver. These results indicate that we need to conduct a more comprehensive assessment of the health risks of pesticide monomers in the future. In a word, these results provide more evidence for assessing the differences in health risks of IMZT enantiomers to mammals as well as provide more references for the promotion and use of pesticide monomers in the future.
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Affiliation(s)
- Chenyang Yao
- College of Science, China Agricultural University, Beijing 100193, China
| | - Jing Sheng
- College of Science, China Agricultural University, Beijing 100193, China
| | - Sen Yan
- College of Science, China Agricultural University, Beijing 100193, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China
| | - Sinuo Tian
- College of Science, China Agricultural University, Beijing 100193, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China
| | - Zhiyuan Meng
- College of Science, China Agricultural University, Beijing 100193, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China
| | - Zhiqiang Zhou
- College of Science, China Agricultural University, Beijing 100193, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China
| | - Wentao Zhu
- College of Science, China Agricultural University, Beijing 100193, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
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18
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Decreased Mitochondrial Function, Biogenesis, and Degradation in Peripheral Blood Mononuclear Cells from Amyotrophic Lateral Sclerosis Patients as a Potential Tool for Biomarker Research. Mol Neurobiol 2020; 57:5084-5102. [PMID: 32840822 PMCID: PMC7541388 DOI: 10.1007/s12035-020-02059-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 08/07/2020] [Indexed: 12/11/2022]
Abstract
Amyotrophic lateral sclerosis (ALS) is a multifactorial and progressive neurodegenerative disease of unknown etiology. Due to ALS’s unpredictable onset and progression rate, the search for biomarkers that allow the detection and tracking of its development and therapeutic efficacy would be of significant medical value. Considering that alterations of energy supply are one of ALS’s main hallmarks and that a correlation has been established between gene expression in human brain tissue and peripheral blood mononuclear cells (PBMCs), the present work investigates whether changes in mitochondrial function could be used to monitor ALS. To achieve this goal, PBMCs from ALS patients and control subjects were used; blood sampling is a quite non-invasive method and is cost-effective. Different parameters were evaluated, namely cytosolic calcium levels, mitochondrial membrane potential, oxidative stress, and metabolic compounds levels, as well as mitochondrial dynamics and degradation. Altogether, we observed lower mitochondrial calcium uptake/retention, mitochondria depolarization, and redox homeostasis deregulation, in addition to a decrease in critical metabolic genes, a diminishment in mitochondrial biogenesis, and an augmentation in mitochondrial fission and autophagy-related gene expression. All of these changes can contribute to the decreased ATP and pyruvate levels observed in ALS PBMCs. Our data indicate that PBMCs from ALS patients show a significant mitochondrial dysfunction, resembling several findings from ALS’ neural cells/models, which could be exploited as a powerful tool in ALS research. Our findings can also guide future studies on new pharmacological interventions for ALS since assessments of brain samples are challenging and represent a relevant limited strategy.
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Retrospective Evaluation of Relationship Between Iron Overload and Transplantation Complications in Pediatric Patient Who Underwent Allogeneic Stem Cell Transplantation Due to Acute Leukemia and Myelodysplastic Syndrome. J Pediatr Hematol Oncol 2020; 42:e315-e320. [PMID: 32427707 DOI: 10.1097/mph.0000000000001829] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. STUDY DESIGN Retrospective observational cohort study. AIMS To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia to assess the necessity of reducing iron load. PATIENTS AND METHODS Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL. RESULTS Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43±9.42 and 118.56±10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P<0.011 for both). Ferritin level was not associated with rates of engraftment syndrome, veno-occlusive disease, early/late infection, relapse, or overall and disease-free survival. CONCLUSIONS In our study, significant result especially in terms of acute liver GVHD, was important to emphasize the need to be more careful in terms of acute liver GVHD risk in early liver pathologies in patients with high levels of ferritin after transplantation. In future large studies may be helpful to explain the relationship between acute liver GVHD and high ferritin levels.
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20
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Zhang R, Zhou Z, Zhu W. Evaluating the effects of the tebuconazole on the earthworm, Eisenia fetida by H-1 NMR-Based untargeted metabolomics and mRNA assay. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 194:110370. [PMID: 32151865 DOI: 10.1016/j.ecoenv.2020.110370] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 02/20/2020] [Accepted: 02/21/2020] [Indexed: 06/10/2023]
Abstract
Tebuconazole, a widely used fungicide, can severely disrupt the reproductive process of various organisms. In this study, we investigated the subacute effects of tebuconazole on the earthworm to fully understand its toxic implications. Herein, untargeted metabolomics, mRNA assay and biochemical approaches were adopted to evaluate the subacute effects of Eisenia fetida earthworms, when exposed to tebuconazole at three different concentrations (0.5, 5 and 50 mg/kg) for seven days. SOD enzyme activity test displayed that tebuconazole exposure interfered with the earthworms' ROS. ANN mRNA expression was down-regulated after tebuconazole exposure. 1H nuclear magnetic resonance (1H-NMR)-based untargeted metabolomics study showed that 5 mg/kg tebuconazole exposure interfered with earthworms' metabolism. Twelve significantly changed metabolites were identified. The pathway analyses indicate that tebuconazole can disrupt the earthworm's metabolism, particularly in the AMP pathway, which impact the reproduction. This may explain the tebuconazole's mechanism of action behind the down-regulation of the expression of ANN mRNA, which is related to the earthworm's reproductive process. We comprehensively evaluated the mRNA expression, enzyme activity, and metabolomics, and acquired sufficient information for evaluating the toxicity of tebuconazole.
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Affiliation(s)
- Renke Zhang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Zhiqiang Zhou
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Wentao Zhu
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China.
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21
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Piotrowski I, Kulcenty K, Suchorska W. Interplay between inflammation and cancer. Rep Pract Oncol Radiother 2020; 25:422-427. [PMID: 32372882 PMCID: PMC7191124 DOI: 10.1016/j.rpor.2020.04.004] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 02/20/2020] [Accepted: 04/02/2020] [Indexed: 02/07/2023] Open
Abstract
Tumor-promoting inflammation is one of the hallmarks of cancer. It has been shown that cancer development is strongly influenced by both chronic and acute inflammation process. Progress in research on inflammation revealed a connection between inflammatory processes and neoplastic transformation, the progression of tumour, and the development of metastases and recurrences. Moreover, the tumour invasive procedures (both surgery and biopsy) affect the remaining tumour cells by increasing their survival, proliferation and migration. One of the concepts explaining this phenomena is an induction of a wound healing response. While in normal tissue it is necessary for tissue repair, in tumour tissue, induction of adaptive and innate immune response related to wound healing, stimulates tumour cell survival, angiogenesis and extravasation of circulating tumour cells. It has become evident that certain types of immune response and immune cells can promote tumour progression more than others. In this review, we focus on current knowledge on carcinogenesis and promotion of cancer growth induced by inflammatory processes.
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Key Words
- ANGPTL4, angiopoietin-like 4
- CDH1, cadherin 1
- COX, cyclooxygenase
- Cancer
- EMT, epithelail to mesenchymal transition
- EP, receptor - prostaglandin receptor
- GI, gastrointensinal cancer
- IL-6, interleukin 6
- Inflammation
- MPO, myeloperoxidase
- NADPH, nicotynamide adenine dinucleotide phosphate hydrogen
- NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells
- NK, natural killer cells
- NO, nitric oxide
- NSAIDs, non-steroidal anti-inflammatory drugs
- PGE2, prostaglandin E2
- PTHrP, parathyroid hormone related protein
- RNS, reactive nitrogen species
- ROS, reactive oxigen species
- STAT3, signal transducer and activator of transcription 3
- TGF-β, transforming growth factor β
- TGFBRII, transforming growth factor, beta receptor II
- TNF-α, tumour necrosis factor α
- TNFR1, Tumor necrosis factor receptor 1
- TNFR2, Tumor necrosis factor receptor 2
- Tumor reccurence
- VEGF, vascular endothelail growth factor
- bFGF, fibroblast growth factor
- iNOS, inducible nitric oxide synthase
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Affiliation(s)
- Igor Piotrowski
- Radiobiology Laboratory, Department of Medical Physics, Greater Poland Cancer Centre, Garbary 15 Street, 61-866 Poznań, Poland.,Department of Electroradiology, University of Medical Sciences, Garbary 15 Street, 61-866 Poznań, Poland
| | - Katarzyna Kulcenty
- Radiobiology Laboratory, Department of Medical Physics, Greater Poland Cancer Centre, Garbary 15 Street, 61-866 Poznań, Poland.,Department of Electroradiology, University of Medical Sciences, Garbary 15 Street, 61-866 Poznań, Poland
| | - Wiktoria Suchorska
- Radiobiology Laboratory, Department of Medical Physics, Greater Poland Cancer Centre, Garbary 15 Street, 61-866 Poznań, Poland.,Department of Medical Physics, Greater Poland Cancer Centre, Garbary 15 Street, 61-866 Poznań, Poland
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22
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Karayigit MO, Dincel GC. Role of ADAMTS-13 and nNOS expression in neuropathogenesis of listeric encephalitis of small ruminants. Biotech Histochem 2020; 95:584-596. [PMID: 32237909 DOI: 10.1080/10520295.2020.1743359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
We investigated the expression of A disintegrin and metalloprotease with thrombospondin type I repeats-13 (ADAMTS-13) in the central nervous system (CNS), because it is related to blood-brain barrier (BBB) permeability. We also investigated 8-OHdG, caspase-3 and neuronal nitric oxide synthase (nNOS) expression for the cytotoxic effects of oxidative stress (OS) and nNOS, and their relation to apoptosis. We also investigated the neuroimmunopathology caused by L. monocytogenes. Brain tissues were obtained from 10 lambs and 10 kids with listeric meningoencephalitis, and healthy brain tissue from six lambs and six kids. Serial sections of brain were stained by hematoxylin and eosin (H & E), and using immunohistochemistry (IHC) for L. monocytogenes antigen, ADAMTS-13, 8-hydroxy-2'-deoxyguanosine (8-OHdG), nNOS and caspase-3. We found that ADAMTS-13, 8-OHdG, nNOS and caspase-3 expression in the brain was increased in L. Monocytogenes infected animals compared to uninfected controls. Intense staining for 8-OHdG was observed only in neurons and glia that were exposed to OS. ADAMTS-13 was increased significantly, which may play a role in regulating and protecting BBB integrity and cells of the CNS in cases of listeric encephalitis. Increased expression of ADAMTS-13 may be critical for supporting the survival of neurons and glia. We found that L. monocytogenes-related increases in OS and nNOS, and that the associated apoptosis, may participate in neurodegeneration and neuropathology in listeric encephalitis.
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Affiliation(s)
- M O Karayigit
- Departmant of Pathology, Faculty of Veterinary Medicine, University of Cumhuriyet , Sivas, Turkey
| | - G C Dincel
- Eskil Vocational High School, University of Aksaray , Eskil, Turkey
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Murali M, Carvalho MS, Shivanandappa T. Oxidative stress-mediated cytotoxicity of Endosulfan is causally linked to the inhibition of NADH dehydrogenase and Na+, K+-ATPase in Ehrlich ascites tumor cells. Mol Cell Biochem 2020; 468:59-68. [DOI: 10.1007/s11010-020-03711-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 03/06/2020] [Indexed: 02/06/2023]
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Yu DY. Relevance of reactive oxygen species in liver disease observed in transgenic mice expressing the hepatitis B virus X protein. Lab Anim Res 2020; 36:6. [PMID: 32206612 PMCID: PMC7081669 DOI: 10.1186/s42826-020-00037-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 02/12/2020] [Indexed: 12/16/2022] Open
Abstract
The hepatitis B virus (HBV) infects approximately 240 million people worldwide, causing chronic liver disease (CLD) and liver cancer. Although numerous studies have been performed to date, unfortunately there is no conclusive drug or treatment for HBV induced liver disease. The hepatitis B virus X (HBx) is considered a key player in inducing CLD and hepatocellular carcinoma (HCC). We generated transgenic (Tg) mice expressing HBx protein, inducing HCC at the age of 11–18 months. The incidence of histological phenotype, including liver tumor, differed depending on the genetic background of HBx Tg mice. Fatty change and tumor generation were observed much earlier in livers of HBx Tg hybrid (C57BL/6 and CBA) (HBx-Tg hybrid) mice than in HBx Tg C57BL/6 (HBx-Tg B6) mice. Inflammation was also enhanced in the HBx-Tg B6 mice as compared to HBx-Tg hybrid mice. HBx may be involved in inducing and promoting hepatic steatosis, glycemia, hepatic fibrosis, and liver cancer. Reactive oxygen species (ROS) generation was remarkably increased in livers of HBx Tg young mice compared to young wild type control mice. Previous studies on HBx Tg mice indicate that the HBx-induced ROS plays a role in inducing and promoting CLD and HCC.
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Affiliation(s)
- Dae-Yeul Yu
- Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806 South Korea
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Li S, Li H, Xu X, Saw PE, Zhang L. Nanocarrier-mediated antioxidant delivery for liver diseases. Theranostics 2020; 10:1262-1280. [PMID: 31938064 PMCID: PMC6956819 DOI: 10.7150/thno.38834] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/30/2019] [Indexed: 12/12/2022] Open
Abstract
Liver is the principal detoxifying organ and metabolizes various compounds that produce free radicals (FR) constantly. To maintain the oxidative/antioxidative balance in the liver, antioxidants would scavenge FR by preventing tissue damage through FR formation, scavenging, or by enhancing their decomposition. The disruption of this balance therefore leads to oxidative stress and in turn leads to the onset of various diseases. Supplying the liver with exogeneous antioxidants is an effective way to recreate the oxidative/antioxidative balance in the liver homeostasis. Nevertheless, due to the short half-life and instability of antioxidants in circulation, the methodology for delivering antioxidants to the liver needs to be improved. Nanocarrier mediated delivery of antioxidants proved to be an ingenious way to safely and efficiently deliver a high payload of antioxidants into the liver for circumventing liver diseases. The objective of this review is to provide an overview of the role of reactive oxygen species (oxidant) and ROS scavengers (antioxidant) in liver diseases. Subsequently, current nanocarrier mediated antioxidant delivery methods for liver diseases are discussed.
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Affiliation(s)
- Senlin Li
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China
| | - Huiru Li
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China
| | - Xiaoding Xu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China
| | - Phei Er Saw
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China
| | - Lei Zhang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China
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Kassa J, Stetina R. The evaluation of oxidative damage of DNA after poisoning with nerve agents. J Appl Biomed 2019; 17:225-230. [PMID: 34907721 DOI: 10.32725/jab.2019.017] [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: 05/29/2019] [Accepted: 11/06/2019] [Indexed: 11/05/2022] Open
Abstract
The potency of three nerve agents (sarin, soman, tabun) to induce oxidative damage of DNA in lymphocytes, liver and brain during lethal or sublethal poisoning was investigated. The single strand breaks or oxidative base DNA damage was evaluated with the help of Comet assay and a specific enzyme able to detect oxidative bases of DNA (endonuclease III). While sarin and soman administered at sublethal doses corresponding to 50% of their LD50 values were not able to induce oxidative damage of DNA, their lethal dose (LD50) induced the significant increase of the number of oxidative bases in DNA of hepatocytes. In addition, tabun administered at lethal dose (LD50) induced significant increase of the number of single strand breaks and oxidative bases of DNA in glial cells isolated from pontomedullar brain region. Thus, some nerve agents were able to induce oxidative damage in the peripheral as well as central compartment but only in the case of severe poisoning caused by lethal doses of nerve agents. This non-cholinergic effect of nerve agents has probably consequences with nerve agents-induced hypoxic status during acute cholinergic crisis and it can contribute to their long-term toxic effects.
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Affiliation(s)
- Jiri Kassa
- University of Defence in Brno, Faculty of Military Health Sciences, Department of Toxicology and Military Pharmacy, Hradec Kralove, Czech Republic
| | - Rudolf Stetina
- University of Defence in Brno, Faculty of Military Health Sciences, Department of Toxicology and Military Pharmacy, Hradec Kralove, Czech Republic
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27
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Santaus TM, Zhang F, Li S, Stine OC, Geddes CD. Effects of Lyse-It on endonuclease fragmentation, function and activity. PLoS One 2019; 14:e0223008. [PMID: 31568482 PMCID: PMC6768537 DOI: 10.1371/journal.pone.0223008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 09/11/2019] [Indexed: 12/31/2022] Open
Abstract
Nucleases are enzymes that can degrade genomic DNA and RNA that decrease the accuracy of quantitative measures of those nucleic acids. Here, we study conventional heating, standard microwave irradiation, and Lyse-It, a microwave-based lysing technology, for the potential to fragment and inactivate DNA and RNA endonucleases. Lyse-It employs the use of highly focused microwave irradiation to the sample ultimately fragmenting and inactivating RNase A, RNase B, and DNase I. Nuclease size and fragmentation were determined visually and quantitatively by SDS polyacrylamide gel electrophoresis and the mini-gel Agilent 2100 Bioanalyzer system, with a weighted size calculated to depict the wide range of nuclease fragmentation. Enzyme activity assays were conducted, and the rates were calculated to determine the effect of various lysing conditions on each of the nucleases. The results shown in this paper clearly demonstrate that Lyse-It is a rapid and highly efficient way to degrade and inactivate nucleases so that nucleic acids can be retained for down-stream detection.
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Affiliation(s)
- Tonya M. Santaus
- Chemistry and Biochemistry Department, University of Maryland, Baltimore County, Baltimore, Maryland, United States of America
- Institute of Fluorescence, University of Maryland, Baltimore County, Baltimore, Maryland, United States of America
| | - Fan Zhang
- Chemistry and Biochemistry Department, University of Maryland, Baltimore County, Baltimore, Maryland, United States of America
| | - Shan Li
- Epidemiology and Public Health Department, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
| | - O. Colin Stine
- Epidemiology and Public Health Department, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
| | - Chris D. Geddes
- Chemistry and Biochemistry Department, University of Maryland, Baltimore County, Baltimore, Maryland, United States of America
- Institute of Fluorescence, University of Maryland, Baltimore County, Baltimore, Maryland, United States of America
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28
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Jia Z, Wang H, Feng Z, Zhang S, Wang L, Zhang J, Liu Q, Zhao X, Feng D, Feng X. Fluorene-9-bisphenol exposure induces cytotoxicity in mouse oocytes and causes ovarian damage. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2019; 180:168-178. [PMID: 31082581 DOI: 10.1016/j.ecoenv.2019.05.019] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/27/2019] [Accepted: 05/07/2019] [Indexed: 06/09/2023]
Abstract
Fluorene-9-bisphenol (BHPF), a substitute for bisphenol A, is a chemical component of plastics for industrial production. There is evidence that BHPF exerts an antioestrogenic effect on mice, induces endometrial atrophy and leads to adverse pregnancy outcomes. However, the effects of BHPF on oocyte maturation and ovary development as well as its possible mechanisms remain unclear. The objective of this study was to investigate the toxicity and mechanism of BHPF exposure in mouse oocytes in vitro and in vivo. Our results showed that BHPF could inhibit the maturation of oocytes in vitro by reducing the protein level of p-MAPK and destroying the meiotic spindle. We found that in vitro, BHPF-treated oocytes showed increased ROS levels, DNA damage, mitochondrial dysfunction, and expression of apoptosis- and autophagy-related genes, such as Bax, cleaved-caspase 3, LC 3 and Atg 12. In addition, in vivo experiments showed that BHPF exposure could induce the expression of oxidative stress genes (Cat, Gpx 3 and Sod 2) and apoptosis genes (Bax, Bcl-2 and Cleaved-caspase 3) and increase the number of atresia follicles in the ovaries. Our data showed that BHPF exposure affected the first polar body extrusion of oocytes, increased oxidative stress, destroyed spindle assembly, caused DNA damage, altered mitochondrial membrane potentials, induced apoptosis and autophagy, and affected ovarian development.
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Affiliation(s)
- Zhenzhen Jia
- State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300 071, China; College of Life Science, Shandong Normal University, Shandong Provincial Key Laboratory of Animal Resistance Biology, Institute of Biomedical Sciences, Key Laboratory of Food Nutrition and Safety of Shandong Normal University, Jinan, 250014, China
| | - Hongyu Wang
- State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300 071, China
| | - Zeyang Feng
- The Institute of Robotics and Automatic Information Systems, Nankai University, Tianjin, 300 071, China
| | - Shaozhi Zhang
- State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300 071, China
| | - Lining Wang
- State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300 071, China
| | - Jingwen Zhang
- State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300 071, China
| | - Qianqian Liu
- State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300 071, China
| | - Xin Zhao
- The Institute of Robotics and Automatic Information Systems, Nankai University, Tianjin, 300 071, China.
| | - Daofu Feng
- Department of General Surgery, Tianjin Medical University General Hospital, No. 154 Anshan Road, Tianjin, 300052, China.
| | - Xizeng Feng
- State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300 071, China.
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Caspa Gokulan R, Garcia-Buitrago MT, Zaika AI. From genetics to signaling pathways: molecular pathogenesis of esophageal adenocarcinoma. Biochim Biophys Acta Rev Cancer 2019; 1872:37-48. [PMID: 31152823 PMCID: PMC6692203 DOI: 10.1016/j.bbcan.2019.05.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 05/10/2019] [Accepted: 05/10/2019] [Indexed: 02/07/2023]
Abstract
Esophageal adenocarcinoma (EAC) has one of the fastest rising incidence rates in the U.S. and many other Western countries. One of the unique risk factors for EAC is gastroesophageal reflux disease (GERD), a chronic digestive condition in which acidic contents from the stomach, frequently mixed with duodenal bile, enter the esophagus resulting in esophageal tissue injury. At the cellular level, progression to EAC is underlined by continuous DNA damage caused by reflux and chronic inflammatory factors that increase the mutation rate and promote genomic instability. Despite recent successes in cancer diagnostics and treatment, EAC remains a poorly treatable disease. Recent research has shed new light on molecular alterations underlying progression to EAC and revealed novel treatment options. This review focuses on the genetic and molecular studies of EAC. The molecular changes that occur during the transformation of normal Barrett's esophagus to esophageal adenocarcinoma are also discussed.
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Affiliation(s)
| | | | - Alexander I Zaika
- Department of Surgery, University of Miami, Miami, FL, United States of America; Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL, United States of America.
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30
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Hou Z, Wei C. De novo comparative transcriptome analysis of a rare cicada, with identification of candidate genes related to adaptation to a novel host plant and drier habitats. BMC Genomics 2019; 20:182. [PMID: 30845906 PMCID: PMC6407286 DOI: 10.1186/s12864-019-5547-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 02/20/2019] [Indexed: 01/18/2023] Open
Abstract
Background Although the importance of host plant chemistry in plant–insect interactions is widely recognized, our understanding about the genetic basis underlying the relationship between changes in midgut proteins and adaptation of plant-feeding insects to novel host plants and habitats is very limited. To address this knowledge gap, the transcriptional profiles of midguts among three populations of the cicada Subpsaltria yangi Chen were compared. Among which, the Hancheng (HC) and Fengxiang (FX) populations occurring in the Loess Plateau feed on Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow, while the population occurring in a much drier habitat in the Helan (HL) Mountains is locally specialized on a chemically divergent plant, Ephedra lepidosperma C. Y. Cheng. Results Based on comparative analysis, 1826 (HL vs HC) differentially expressed genes (DEGs) and 723 DEGs (HL vs FX) were identified between the populations utilizing different host plants, including 20, 36, 2, 5 and 2 genes related to digestion, detoxification, oxidation-reduction, stress response and water-deprivation response, respectively, and 35 genes presumably associated with osmoregulation. However, only 183 DEGs were identified between the HC and FX populations, including two genes related to detoxification, two genes related to stress response, and one gene presumably associated with osmoregulation. These results suggest that the weakest expression differences were between the populations utilizing the same host plant and occurring in the closest habitats, which may help explain the metabolic mechanism of adaptation in S. yangi populations to novel host plants and new niches. Conclusions The observed differences in gene expression among S. yangi populations are consistent with the hypothesis that the host plant shift and habitat adaptation in the HL population was facilitated by differential regulation of genes related to digestion, detoxification, oxidation-reduction, stress response, water-deprivation response and osmoregulation. The results may inform future studies on the molecular mechanisms underlying the relationship between changes in midgut proteins and adaptation of herbivorous insects to novel host plants and new niches. Electronic supplementary material The online version of this article (10.1186/s12864-019-5547-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Zehai Hou
- State Key Laboratory of Crop Stress Biology for Arid Areas, and Key Laboratory of Plant Protection Resources and Pest Management, Ministry of Education, College of Plant Protection, Northwest A&F University, Yangling, 712100, Shaanxi, China
| | - Cong Wei
- State Key Laboratory of Crop Stress Biology for Arid Areas, and Key Laboratory of Plant Protection Resources and Pest Management, Ministry of Education, College of Plant Protection, Northwest A&F University, Yangling, 712100, Shaanxi, China.
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31
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Yousef HA, Abdelfattah EA, Augustyniak M. Antioxidant enzyme activity in responses to environmentally induced oxidative stress in the 5th instar nymphs of Aiolopus thalassinus (Orthoptera: Acrididae). ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2019; 26:3823-3833. [PMID: 30539392 DOI: 10.1007/s11356-018-3756-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 11/13/2018] [Indexed: 06/09/2023]
Abstract
The response of antioxidant enzymes to oxidative environmental stress was determined in 5th instar nymphs of Aiolopus thalassinus (Orthoptera: Acrididae) collected from sites with different level of pollution with heavy metals, PO43-, and SO42-. The high polluted site induced higher DNA damage to individuals compared to the control site. The highest values of tail length (TL), tail moment (TM), and percent of DNA in tail (TDNA) were found in the gut of 5th instar nymphs from a high polluted site. Also, protein carbonyls and lipid peroxide levels were significantly higher in insects collected from polluted sites compared to those from the control site. A strong positive correlation between both protein carbonyl and lipid peroxide concentration and the pollution level of the sites was found in all tissues of the insects. The activity of superoxide dismutase (SOD) in the brain of insects collected from the high polluted site was significantly higher than that in the thoracic muscles and gut. We observed strong inhibition of catalase (CAT) activity. This effect was apparently caused by pollutants present at the high polluted site. The level of pollution significantly influenced polyphenol oxidase (PPO) activity in A. thalassinus nymphs in all examined tissues. The highest values were observed in the brain. The relationship between pollution and ascorbate peroxidase (APOX) activity in the examined tissues had no clear tendency. However, the lowest APOX activity was observed in individuals from the low polluted site. Level of pollution of sampling sites, oxidative stress biomarkers, and enzymatic response in A. thalanthsis 5th instar were negatively or positively correlated. Oxidative damage parameters, especially the percent of severed cells, lipid peroxides, and the activity of APOX, can be perceived as good markers of environmental multistress.
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Affiliation(s)
- Hesham A Yousef
- Entomology Department, Faculty of Science, Cairo University, Giza, Egypt.
| | - Eman A Abdelfattah
- Entomology Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Maria Augustyniak
- Department of Animal Physiology and Ecotoxicology, University of Silesia in Katowice, Katowice, Poland
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32
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Karami-Gadallo L, Ataie-Fashtami L, Ghoranneviss M, Pouladian M, Sardari D. Cell damaging by irradiating non-thermal plasma to the water: Mathematical modeling of chemical processes. MOLECULAR BIOLOGY RESEARCH COMMUNICATIONS 2018; 7:133-141. [PMID: 30426031 DOI: 10.22099/mbrc.2018.29751.1325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Abstract
Recently non-thermal plasma (NTP) is applied for many therapeutic applications. By NTP irradiating to the tissues or cell-lines, the water molecules (H2O) would be also activated leading to generate hydrogen peroxide (H2O2). By irradiating plasma to bio-solution, its main output including vacuum UV to UV causes the photolysis of H2O leading to generate hydroxyl (OH) molecules in couple forms with ability to convert to H2O2. Additionally, other plasma's output the oxygen atoms could also penetrate under the liquid's surface and react with H2O to generate H2O2. In NTP applications for killing unwanted-cells of microorganisms (e.g. sterilization) or cancerous tissues, the H2O2 molecule is the main reactive species for cell death via inducing DNA damage in mammalian cells. In this paper we proposed a mathematical model for NTP application describing the formation of hydroxyls in the bio solution and other subsequent reactions leading to DNA damage in vitro. The instant concentrations of the OH and H2O2, the main species for DNA oxidation were obtained and investigated in this simulation. In order to validate the model, the cellular response to NTP stimulation was compared with some experimental findings from viewpoint of DNA damage to show the significant consistency.
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Affiliation(s)
- Leila Karami-Gadallo
- Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Leila Ataie-Fashtami
- Department of Regenerative Medicine, Royan Institute for Stem Cell Biology & Technology, Tehran, Iran
| | - Mahmood Ghoranneviss
- Department of Plasma Physics, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Majid Pouladian
- Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.,Research Center of 'Engineering in Medicine and Biology', Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Dariush Sardari
- Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
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Tiwari MK, Mishra PC. Scavenging of hydroxyl, methoxy, and nitrogen dioxide free radicals by some methylated isoflavones. J Mol Model 2018; 24:287. [DOI: 10.1007/s00894-018-3805-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 08/21/2018] [Indexed: 11/25/2022]
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Zhang J, Wang L, Zhou Q, Huang X. Reactive oxygen species initiate a protective response in plant roots to stress induced by environmental bisphenol A. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2018; 154:197-205. [PMID: 29475125 DOI: 10.1016/j.ecoenv.2018.02.020] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2017] [Revised: 02/04/2018] [Accepted: 02/05/2018] [Indexed: 05/12/2023]
Abstract
Bisphenol A (BPA), a contaminant of emerging concern, can affect plant growth and development at high concentrations. Reactive oxygen species (ROS) production is a general primary response in plants to stress. Here, the aim is to investigate whether ROS in plants play protective roles for stress induced by BPA exposure at environmental concentrations. In this study, soybean roots (seedling, flowering and podding stages) were exposed to 1.5 and 3.0 mg L-1 BPA, and ROS response was measured. The relationship between ROS levels and residual BPA content in soybean roots was evaluated. The results showed that exposure (9 h) to 1.5 mg L-1 BPA elicited changes in ROS production. ROS then gradually accumulated in soybean roots (seedling stage). Exposure to 3.0 mg L-1 BPA elicited a stronger and earlier ROS responses at the flowering and podding stage, but did not lead to membrane lipid peroxidation. Residual BPA content in soybean roots reached peak concentrations after 9 h of exposure, and then gradually decreased at the flowering and podding stage. These results indicate that ROS in soybean roots might be involved in the oxidative metabolism of BPA, which could prevent BPA from damaging exposed plants. In conclusion, the observed ROS metabolic effects may be self-protection responses of plants to stress induced by BPA exposure.
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Affiliation(s)
- Jiazhi Zhang
- State Key Laboratory of Food Science and Technology, Jiangsu Key Laboratory of Anaerobic Biotechnology, School of Environment and Civil Engineering, Jiangnan University, Wuxi 214122, China; Jiangsu Cooperative Innovation Center of Water Treatment Technology and Materials, Suzhou University of Science and Technology, Suzhou 215009, China
| | - Lihong Wang
- State Key Laboratory of Food Science and Technology, Jiangsu Key Laboratory of Anaerobic Biotechnology, School of Environment and Civil Engineering, Jiangnan University, Wuxi 214122, China; Jiangsu Cooperative Innovation Center of Water Treatment Technology and Materials, Suzhou University of Science and Technology, Suzhou 215009, China
| | - Qing Zhou
- State Key Laboratory of Food Science and Technology, Jiangsu Key Laboratory of Anaerobic Biotechnology, School of Environment and Civil Engineering, Jiangnan University, Wuxi 214122, China.
| | - Xiaohua Huang
- Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biomedical Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210046, China.
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Guan G, Lan S. Implications of Antioxidant Systems in Inflammatory Bowel Disease. BIOMED RESEARCH INTERNATIONAL 2018; 2018:1290179. [PMID: 29854724 PMCID: PMC5966678 DOI: 10.1155/2018/1290179] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 04/04/2018] [Indexed: 01/16/2023]
Abstract
The global incidence of inflammatory bowel disease (IBD), a group of chronic gastrointestinal disorders, has been rising. The preponderance of evidence demonstrates that oxidative stress (OS) performs a critical function in the onset of IBD and the manner of its development. The purpose of this review is to outline the generation of reactive oxygen species and antioxidant defense mechanisms in the gastrointestinal tract and the role played by OS in marking the onset and development of IBD. Furthermore, the review demonstrates the various ways through which OS is related to genetic susceptibility and the mucosal immune response. The experimental results suggest that certain therapeutic regimens for IBD could have a favorable impact by scavenging free radicals, reducing cytokine and prooxidative enzyme concentrations, and improving the antioxidative capabilities of cells. However, antioxidative activity characterized by a high level of specificity may be fundamental for the development of clinical therapies and for relapsing IBD patients. Therefore, additional research is required to clarify the ways through which OS is related to the pathogenesis and progression of IBD.
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Affiliation(s)
- Guiping Guan
- College of Bioscience and Biotechnology and College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China
| | - Shile Lan
- College of Bioscience and Biotechnology and College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China
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36
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Fuchi Y, Fukuda T, Sasaki S. Luminescent europium sensors for specific detection of 8-oxo-dGTP by time-gated fluorescence. Bioorg Med Chem 2018; 26:3254-3260. [PMID: 29731311 DOI: 10.1016/j.bmc.2018.04.052] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 04/25/2018] [Accepted: 04/26/2018] [Indexed: 01/08/2023]
Abstract
The 9-hydroxy-1,3-diazaphenoxazine-2-one unit was conjugated with the Eu3+-cyclen complex through a linker. This diazaphenoxazine group was expected as an antenna unit for the excitation of europium ion, and a selective recognition site for 8-oxo-dGTP base. Among the synthesized three derivatives, the highest fluorescence emission was obtained by the complex constructed of an ethylene linker and the cyclen unit with three N,N-dimethylacetamide groups. The Eu3+-cyclen complex exhibited a selective response to the 8-oxo-dGTP in aqueous media by a time-resolved fluorescence assay.
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Affiliation(s)
- Yasufumi Fuchi
- Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Takashi Fukuda
- Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Shigeki Sasaki
- Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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37
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Chemsa AE, Zellagui A, Öztürk M, Erol E, Ceylan O, Duru ME, Lahouel M. Chemical composition, antioxidant, anticholinesterase, antimicrobial and antibiofilm activities of essential oil and methanolic extract of Anthemis stiparum subsp. sabulicola (Pomel) Oberpr. Microb Pathog 2018; 119:233-240. [PMID: 29684540 DOI: 10.1016/j.micpath.2018.04.033] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 03/29/2018] [Accepted: 04/18/2018] [Indexed: 10/17/2022]
Abstract
Anthemis species are traditionally used to treat infectious and inflammatory processes, among others clinical disturbances. In the current study, the chemical composition, the total phenolic and flavonoid contents, the antioxidant, anticholinesterase, antimicrobial, and antibiofilm activities of Anthemis stiparum subsp. sabulicola aerial parts methanolic extract (As-ME) and essential oil (As-EO) were investigated. The chemical composition of As-EO was established by GC-MS and GC-FID. Total phenolic and flavonoid contents of As-ME were spectrophotometrically determined. Diphenyl-1-picrylhydrazyl (DPPH●) radical scavenging, cupric reducing antioxidant capacity (CUPRAC) and β-carotene bleaching assays were applied to evaluate the antioxidant potential. The anticholinesterase activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were carried out spectrophotometrically. The antimicrobial activity was assessed by Minimal Inhibitory Concentration (MIC) using broth microdilution method against 7 ATCC® bacterial and one ATCC® yeast reference strains. The antibiofilm effect was determined quantifying the percentage of adhesion inhibition. GC-MS and GC-FID identified 72 compounds (99.02%), being As-EO predominantly constituted by germacrene D (11.13%), t-cadinol (11.01%), camphor (6.73%), spathulenol (6.50%) and isoamyl salicylate (6.45%). The total phenolic and flavonoid contents of As-ME were 13.6 ± 0.03 and 5.9 ± 0.04 pyrocatechol equivalents and quercetin equivalents, respectively. In β-carotene-linoleic acid assay, As-ME showed the best lipid peroxidation inhibition activity with an IC50 = 9.96 μg/mL followed by As-EO with an IC50 = 619.98 μg/mL. In contrast, in DPPH assay, As-ME and As-EO showed moderate to low activity with an IC50 = 92.69 μg/mL for As-ME and 917.69 μg/mL for As-EO. While in CUPRAC assay, As-EO and As-ME indicated a less to moderate reducing activity. As-ME inhibited AChE (IC50 = 490.46 μg/mL) and BChE (IC50 = 142.07 μg/mL), while As-EO was inactive against AChE and revealed a discreet inhibitory action against BChE (IC50 = 212.14 μg/mL). As-ME displayed better antimicrobial activity than As-EO, being active against Staphylococcus aureus (ATCC® 25923) and Bacillus subtilis (ATCC® 6633), with MIC of 1.56 mg/mL. An expressive fungal adhesion inhibition (80.02%) on Candida albicans (ATCC® 10239) was detected with As-ME at 6.25 mg/mL. These results showed that A. stiparum subsp. sabulicola is a natural source of active compounds with antibiotic and antibiofilm effects against S. aureus and B. subtilis, and C. albicans, respectively, and also presents antioxidant and anticholinesterase properties.
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Affiliation(s)
- Ahmed Elkhalifa Chemsa
- Department of Biology, Faculty of Life and Natural Sciences, El Oued University, Algeria.
| | - Amar Zellagui
- Laboratory of Biomolecules and Plant Breeding, Faculty of Exact Science and Life Science and Nature, University of Larbi Ben Mhidi, Oum El Bouaghi, Algeria
| | - Mehmet Öztürk
- Department of Chemistry, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey
| | - Ebru Erol
- Department of Chemistry, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey
| | - Ozgür Ceylan
- Department of Plant and Animal Breeding, Ula Ali Kocman Vocational School, Mugla Sitki Kocman University, Mugla, Turkey
| | - Mehmet Emin Duru
- Department of Chemistry, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey
| | - Mesbah Lahouel
- Molecular Toxicology Laboratory, University of Jijel, Algeria
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Pan CH, Jeng HA, Lai CH. Biomarkers of oxidative stress in electroplating workers exposed to hexavalent chromium. JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY 2018; 28:76-83. [PMID: 28120834 DOI: 10.1038/jes.2016.85] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 12/14/2016] [Accepted: 12/19/2016] [Indexed: 06/06/2023]
Abstract
This study evaluates levels of biomarkers of oxidative DNA damage and lipid peroxidation in 105 male workers at 16 electroplating companies who had been exposed to hexavalent chromium (Cr(VI)). The study participants were 230 non-smoking male workers, comprising 105 electroplating workers who had been exposed to chromium and 125 control subjects who performed office tasks. Personal air samples, spot urine samples, hair samples, fingernail samples and questionnaires were used to quantify exposure to Cr(VI), oxidative DNA damage, lipid peroxidation, and environmental pollutants. Both the geometric mean personal concentrations of Cr(VI) of the Cr-exposed workers and the total Cr concentrations in the air to which they were exposed significantly exceeded those for the control subjects. The geometric mean concentrations of Cr in urine, hair and fingernails, and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malondialdehyde (MDA) levels in the Cr(VI) exposed workers exceeded those in the control subjects. Daily cumulative Cr(VI) exposure and urinary Cr were significantly correlated with urinary 8-OHdG levels following adjustments for covariates. A ten-fold increase in urinary Cr level was associated with a 1.73-fold increase in urinary 8-OHdG level. Daily cumulative Cr(VI) exposure and urinary Cr level were significantly correlated with urinary MDA level following adjustments for covariates. A ten-fold increase in urinary Cr was associated with a 1.45-fold increase in urinary MDA. Exposure to Cr(VI) increased oxidative DNA injury and the oxidative deterioration of lipids in electroplating workers.
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Affiliation(s)
- Chih-Hong Pan
- Institute of Labor, Occupational Safety and Health, Ministry of Labor, New Taipei City, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Hueiwang Anna Jeng
- School of Community and Environmental Health, College of Health Sciences, Old Dominion University, Norfolk, Virginia, USA
| | - Ching-Huang Lai
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
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Herraiz T, Galisteo J. Nitrosative deamination of 2'-deoxyguanosine and DNA by nitrite, and antinitrosating activity of β-carboline alkaloids and antioxidants. Food Chem Toxicol 2017; 112:282-289. [PMID: 29277703 DOI: 10.1016/j.fct.2017.12.042] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Revised: 12/20/2017] [Accepted: 12/21/2017] [Indexed: 02/01/2023]
Abstract
Endogenous and dietary nitrite produces reactive nitrogen species (RNS) that react with DNA causing mutations. The nitrosation of 2'-deoxyguanosine (dGuo) and DNA with nitrite was studied under different conditions, and the reaction and degradation products identified and analysed by HPLC-DAD-MS. Nitrosative deamination of dGuo produced xanthine along with 2'-deoxyxanthosine whereas DNA afforded xanthine. Formation of xanthine increased with nitrite concentration and in low pH such as that of stomach. Xanthine was measured as a marker of nitrosation of dGuo and DNA, and it was subsequently used to study the antinitrosating activity of β-carboline alkaloids, and selected antioxidants. Food-occurring tetrahydro-β-carbolines (THβCs) decreased nitrosative deamination of dGuo and DNA under conditions simulating the stomach. Antinitrosating activity was also evidenced for flavonoids (catechin, quercetin) and indole (melatonin) antioxidants. Among THβCs the most active antinitrosating compounds were 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acids (THβC-3-COOHs) that reacted with nitrite to give N-nitroso derivatives as main products along with 3,4-dihydro-β-carboline-3-carboxylic acids and aromatic β-carbolines (norharman and harman). Antinitrosating activity of THβCs correlated well with the formation of N-nitroso-THβC-3-COOHs. These N-nitroso derivatives were stable at pH 7 but degraded in acid conditions affording nitrosating species.
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Affiliation(s)
- Tomás Herraiz
- Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), Spanish National Research Council (CSIC), Juan de la Cierva 3, 28006, Madrid, Spain.
| | - Juan Galisteo
- Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), Spanish National Research Council (CSIC), Juan de la Cierva 3, 28006, Madrid, Spain
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Grochowski C, Litak J, Kamieniak P, Maciejewski R. Oxidative stress in cerebral small vessel disease. Role of reactive species. Free Radic Res 2017; 52:1-13. [PMID: 29166803 DOI: 10.1080/10715762.2017.1402304] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Cerebral small vessel disease (CSVD) is a wide term describing the condition affecting perforating arterial branches as well as arterioles, venules, and capillaries. Cerebral vascular net is one of the main targets of localised oxidative stress processes causing damage to vasculature, changes in the blood flow and blood-brain barrier and, in consequence, promoting neurodegenerative alterations in the brain tissue. Numerous studies report the fact of oxidation to proteins, sugars, lipids and nucleic acids, occurring in most neurodegenerative diseases mainly in the earliest stages and correlations with the development of cognitive and motor disturbances. The dysfunction of endothelium can be caused by oxidative stress and inflammatory mechanisms as a result of reactions and processes generating extensive reactive oxygen species (ROS) production such as high blood pressure, oxidised low density lipoproteins (oxLDL), very low density lipoproteins (vLDL), diabetes, homocysteinaemia, smoking, and infections. Several animal studies show positive aspects of ROS, especially within cerebral vasculature.
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Affiliation(s)
- Cezary Grochowski
- a Department of Neurosurgery and Pediatric Neurosurgery , Medical University of Lublin , Lublin , Poland.,b Department of Human Anatomy , Medical University of Lublin , Lublin , Poland
| | - Jakub Litak
- a Department of Neurosurgery and Pediatric Neurosurgery , Medical University of Lublin , Lublin , Poland
| | - Piotr Kamieniak
- a Department of Neurosurgery and Pediatric Neurosurgery , Medical University of Lublin , Lublin , Poland
| | - Ryszard Maciejewski
- b Department of Human Anatomy , Medical University of Lublin , Lublin , Poland
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Assi M. The differential role of reactive oxygen species in early and late stages of cancer. Am J Physiol Regul Integr Comp Physiol 2017; 313:R646-R653. [DOI: 10.1152/ajpregu.00247.2017] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 08/15/2017] [Accepted: 08/20/2017] [Indexed: 12/31/2022]
Abstract
The large doses of vitamins C and E and β-carotene used to reduce reactive oxygen species (ROS) production and oxidative damages in cancerous tissue have produced disappointing and contradictory results. This therapeutic conundrum was attributed to the double-faced role of ROS, notably, their ability to induce either proliferation or apoptosis of cancer cells. However, for a ROS-inhibitory approach to be effective, it must target ROS when they induce proliferation rather than apoptosis. On the basis of recent advances in redox biology, this review underlined a differential regulation of prooxidant and antioxidant system, respective to the stage of cancer. At early precancerous and neoplastic stages, antioxidant activity decreases and ROS appear to promote cancer initiation via inducing oxidative damage and base pair substitution mutations in prooncogenes and tumor suppressor genes, such as RAS and TP53, respectively. Whereas in late stages of cancer progression, tumor cells escape apoptosis by producing high levels of intracellular antioxidants, like NADPH and GSH, via the pentose phosphate pathway to buffer the excessive production of ROS and related intratumor oxidative injuries. Therefore, antioxidants should be prohibited in patients with advanced stages of cancer and/or undergoing anticancer therapies. Interestingly, the biochemical and biophysical properties of some polyphenols allow them to selectively recognize tumor cells. This characteristic was exploited to design and deliver nanoparticles coated with low doses of polyphenols and containing chemotherapeutic drugs into tumor-bearing animals. First results are encouraging, which may revolutionize the conventional use of antioxidants in cancer.
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Affiliation(s)
- Mohamad Assi
- Laboratory “Movement, Sport and Health Sciences,” University of Rennes II-Ecole Normale Superieur Rennes, France
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Ding ZM, Jiao XF, Wu D, Zhang JY, Chen F, Wang YS, Huang CJ, Zhang SX, Li X, Huo LJ. Bisphenol AF negatively affects oocyte maturation of mouse in vitro through increasing oxidative stress and DNA damage. Chem Biol Interact 2017; 278:222-229. [DOI: 10.1016/j.cbi.2017.10.030] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 10/17/2017] [Accepted: 10/30/2017] [Indexed: 02/02/2023]
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Aldhaheri SR, Jeelani R, Kohan-Ghadr HR, Khan SN, Mikhael S, Washington C, Morris RT, Abu-Soud HM. Dimercapto-1-propanesulfonic acid (DMPS) induces metaphase II mouse oocyte deterioration. Free Radic Biol Med 2017; 112:445-451. [PMID: 28844937 DOI: 10.1016/j.freeradbiomed.2017.08.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/16/2017] [Accepted: 08/18/2017] [Indexed: 12/21/2022]
Abstract
In light of the recent lead contamination of the water in Flint, Michigan and its potential adverse outcomes, much research and media attention has turned towards the safety profile of commonly used chelators. Dimercapto-1-propanesulfonic acid (DMPS) typically used in the treatment of lead, mercury and arsenic poisoning also displays a high affinity towards transition metals such as zinc and copper, essential for biological functioning. It is given in series of dosages (0.2-0.4g/day) over a long period, and has the ability to enter cells. In this work, we investigated the mechanism through which increasing concentrations of DMPS alter oocyte quality as judged by changes in microtubule morphology (MT) and chromosomal alignment (CH) of metaphase II mice oocyte. The oocytes were directly exposed to increasing concentration of DMPS (10, 25, 50, 100 and 300μM) for four hours (time of peak plasma concentration after administration) and reactive oxygen species (mainly hydroxyl radical and superoxide) and zinc content were measured. This data showed DMPS plays an important role in deterioration of oocyte quality through a mechanism involving zinc deficiency and enhancement of reactive oxygen species a major contributor to oocyte damage. Our current work, for the first time, demonstrates the possibility of DMPS to negatively impact fertility. This finding can not only help in counseling reproductive age patients undergoing such treatment but also in the development of potential therapies to alleviate oxidative damage and preserve fertility in people receiving heavy metal chelators.
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Affiliation(s)
- Sarah R Aldhaheri
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Roohi Jeelani
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Hamid-Reza Kohan-Ghadr
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Sana N Khan
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Sasha Mikhael
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Christina Washington
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Robert T Morris
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA; Karmanos Cancer Institute, Detroit, MI 48201, USA
| | - Husam M Abu-Soud
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
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Abdelfattah EA, Augustyniak M, Yousef HA. Biomonitoring of genotoxicity of industrial fertilizer pollutants in Aiolopus thalassinus (Orthoptera: Acrididae) using alkaline comet assay. CHEMOSPHERE 2017; 182:762-770. [PMID: 28535484 DOI: 10.1016/j.chemosphere.2017.05.082] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 04/17/2017] [Accepted: 05/13/2017] [Indexed: 06/07/2023]
Abstract
Phosphate fertilizer industry is considered as one of the main sources of environmental pollutants. Besides solid waste products, e.g. phosphates, sulphates, and heavy metals, also atmospheric pollutants, such as hydrofluoric acid fumes (HF), sulphur dioxide (SO2), nitrogen oxides (NO2), and particulate matter with diameter up to 10 μm (PM10) can be dangerous. Genotoxic effect of these pollutants was monitored by assessing the DNA damage using alkaline comet assay on cells from brain, thoracic muscles and gut of Aiolopus thalassinus collected at three sites (A-C) located at 1, 3, and 6 km away from Abu-Zaabal Company for Fertilizers and Chemical Industries. Control site was established 32 km from the source of pollution, at the Cairo University Campus. The level of the DNA damage was significantly higher in insects from polluted sites comparing to that from the control site. A strong negative correlation between percentage of cells with visible DNA damage (% of severed cells) and the distance of the sites from Abu-Zaabal Company was found. The best parameter for monitoring of fertilizer pollutants is % of severed cells. Possible impact of Abu-Zaabal Company (extremely high concentration of phosphates and sulphates in all the polluted sites) on DNA integrity in A. thalassinus tissues was discussed. The potential use of the comet assay as a biomonitoring method of the environmental pollution caused by fertilizer industry was proposed. Specific pollution resulting from the activity of the fertilizer industry can cause comparable adverse effects in the organisms inhabiting areas up to 6 km from the source of contamination.
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Affiliation(s)
| | - Maria Augustyniak
- Department of Animal Physiology and Ecotoxicology, University of Silesia in Katowice, Bankowa 9, PL 40-007 Katowice, Poland
| | - Hesham A Yousef
- Entomology Department, Faculty of Science, Cairo University, Egypt.
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Kawanishi S, Ohnishi S, Ma N, Hiraku Y, Murata M. Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis. Int J Mol Sci 2017; 18:E1808. [PMID: 28825631 PMCID: PMC5578195 DOI: 10.3390/ijms18081808] [Citation(s) in RCA: 187] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 08/09/2017] [Accepted: 08/10/2017] [Indexed: 12/21/2022] Open
Abstract
Inflammation can be induced by chronic infection, inflammatory diseases and physicochemical factors. Chronic inflammation is estimated to contribute to approximately 25% of human cancers. Under inflammatory conditions, inflammatory and epithelial cells release reactive oxygen (ROS) and nitrogen species (RNS), which are capable of causing DNA damage, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-nitroguanine. We reported that 8-nitroguanine was clearly formed at the sites of cancer induced by infectious agents including Helicobacter pylori, inflammatory diseases including Barrett's esophagus, and physicochemical factors including asbestos. DNA damage can lead to mutations and genomic instability if not properly repaired. Moreover, DNA damage response can also induce high mobility group box 1-generating inflammatory microenvironment, which is characterized by hypoxia. Hypoxia induces hypoxia-inducible factor and inducible nitric oxide synthase (iNOS), which increases the levels of intracellular RNS and ROS, resulting DNA damage in progression with poor prognosis. Furthermore, tumor-producing inflammation can induce nuclear factor-κB, resulting in iNOS-dependent DNA damage. Therefore, crosstalk between DNA damage and inflammation may play important roles in cancer development. A proposed mechanism for the crosstalk may explain why aspirin decreases the long-term risk of cancer mortality.
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Affiliation(s)
- Shosuke Kawanishi
- Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan.
| | - Shiho Ohnishi
- Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan.
| | - Ning Ma
- Division of Health Science, Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan.
| | - Yusuke Hiraku
- Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
| | - Mariko Murata
- Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
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Moniruzzaman M, Lee JH, Lee JH, Won S, Damusaru JH, Bai SC. Interactive effect of dietary vitamin E and inorganic mercury on growth performance and bioaccumulation of mercury in juvenile olive flounder, Paralichthys olivaceus treated with mercuric chloride. ACTA ACUST UNITED AC 2017; 3:276-283. [PMID: 29767088 PMCID: PMC5941236 DOI: 10.1016/j.aninu.2017.07.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 06/30/2017] [Accepted: 07/03/2017] [Indexed: 11/02/2022]
Abstract
A 6-week feeding trial was carried out to evaluate the effects of dietary vitamin E (dl-α-tocopheryl acetate, TA) on growth and mercury (Hg) accumulation in juvenile olive flounder (Paralichthys olivaceus) treated with mercuric chloride (HgCl2). Vitamin E and HgCl2 were added to the semi-purified basal diet. Six semi-purified diets in a 2 × 3 factorial design were formulated to contain 2 levels of Hg (0 or 20 mg HgCl2/kg diet) and 3 levels of vitamin E (0, 100, or 200 mg TA/kg diet). Experimental fish (n = 360, 9.99 ± 0.15 g) were randomly allocated into 30-L tanks at a density of 20 fish per tank with 3 replicates in each treatment and were fed twice a day. At the end of the feeding trial, dietary Hg depressed the growth performances in terms of weight gain (WG), specific growth rate (SGR), feed efficiency (FE) and protein efficiency ratio (PER) in fish, while fish fed the diets supplemented with vitamin E showed significant growth improvement in both presence and absence of HgCl2 in the diets (P < 0.05). Survival rate was not affected in fish fed the experimental diets. Whole body compositions of fish such as lipid and moisture contents were influenced by dietary vitamin E supplementation. Total Hg contents of muscle, liver and kidney tissues were significantly reduced in fish fed diets supplemented with vitamin E (P < 0.05), while the two-way ANOVA showed that increasing Hg concentration has resulted in a reduction in vitamin E. Whole body fatty acids of fish like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contents were decreased by dietary Hg. However, supplementation of dietary vitamin E improved the α-linolenic acid (ALA) and EPA contents in fish. Our results suggest that dietary supplementation of vitamin E has potential effects on growth improvement and ameliorating inorganic Hg bioaccumulation in juvenile olive flounder.
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Affiliation(s)
- Mohammad Moniruzzaman
- Department of Marine Bio-materials and Aquaculture, Feeds & Foods Nutrition Research Center, Pukyong National University, Busan 608-737, Republic of Korea
| | - Jun-Ho Lee
- Department of Marine Bio-materials and Aquaculture, Feeds & Foods Nutrition Research Center, Pukyong National University, Busan 608-737, Republic of Korea
| | - Jin-Hyeok Lee
- Department of Marine Bio-materials and Aquaculture, Feeds & Foods Nutrition Research Center, Pukyong National University, Busan 608-737, Republic of Korea
| | - Seonghun Won
- Department of Marine Bio-materials and Aquaculture, Feeds & Foods Nutrition Research Center, Pukyong National University, Busan 608-737, Republic of Korea
| | - Jim H Damusaru
- Department of Marine Bio-materials and Aquaculture, Feeds & Foods Nutrition Research Center, Pukyong National University, Busan 608-737, Republic of Korea
| | - Sungchul C Bai
- Department of Marine Bio-materials and Aquaculture, Feeds & Foods Nutrition Research Center, Pukyong National University, Busan 608-737, Republic of Korea
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47
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Xue Y, Zhang S, Du M, Zhu MJ. Dandelion extract suppresses reactive oxidative species and inflammasome in intestinal epithelial cells. J Funct Foods 2017. [DOI: 10.1016/j.jff.2016.11.032] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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48
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Aouey B, Derbali M, Chtourou Y, Bouchard M, Khabir A, Fetoui H. Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2017; 24:5841-5856. [PMID: 28058584 DOI: 10.1007/s11356-016-8323-4] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 12/21/2016] [Indexed: 05/27/2023]
Abstract
Lambda-cyhalothrin (LTC) [α-cyano-3-phenoxybenzyl-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclo-propanecarboxylate] is a synthetic type II pyrethroid insecticide commonly used in residential and agricultural areas. The potential hepatotoxicity of pyrethroids remains unclear and could easily be assessed by measuring common clinical indicators of liver disease. To understand more about the potential risks for humans associated with LTC exposure, male adult rats were orally exposed to 6.2 and 31.1 mg/kg bw of LTC for 7, 30, 45, and 60 days. Histopathological changes and alterations of main parameters related to oxidative stress and inflammatory responses in the liver were evaluated. Further, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] in the liver tissues were identified and quantified by ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC-MS-Q-ToF). Results revealed that LTC exposure significantly increased markers of hepatic oxidative stress in a time-dependent and dose-dependent manner, and this was associated with an accumulation of CFMP and 3-PBA in the liver tissues. In addition, the levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6 and IL-1β) gene expressions were significantly increased in the liver of exposed rats compared to controls. Correlation analyses revealed that CFMP and 3-PBA metabolite levels in the liver tissues were significantly correlated with the indexes of oxidative stress, redox status, and inflammatory markers in rats exposed to lambda-cyhalothin. Overall, this study provided novel evidence that hepatic damage is likely due to increased oxidative stress and inflammation under the condition of acute and subchronic exposure to lambda-cyhalothrin and that LTC metabolites (CFMP and 3-PBA) could be used as potential biomarker in human biomonitoring studies.
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Affiliation(s)
- Bakhta Aouey
- Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia
| | - Mohamed Derbali
- Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia
| | - Yassine Chtourou
- Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia
| | - Michèle Bouchard
- Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management and Research Institute of Public Health of the University of Montreal (IRSPUM), University of Montreal, Montreal, QC, Canada
| | - Abdelmajid Khabir
- Laboratory of Histopathology, Habib Bourguiba Hospital, 4010, Medenine, Tunisia
| | - Hamadi Fetoui
- Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia.
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Kawanishi S, Ohnishi S, Ma N, Hiraku Y, Oikawa S, Murata M. Nitrative and oxidative DNA damage in infection-related carcinogenesis in relation to cancer stem cells. Genes Environ 2017; 38:26. [PMID: 28050219 PMCID: PMC5203929 DOI: 10.1186/s41021-016-0055-7] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 07/27/2016] [Indexed: 02/07/2023] Open
Abstract
Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells, and result in the formation of oxidative and nitrative DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1), including bacterium Helicobacter pylori (H. pylori), viruses [hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV) and Epstein-Barr virus (EBV)] and parasites [Schistosoma haematobium (SH) and Opisthorchis viverrini (OV)]. H. pylori, HBV/HCV, HPV, EBV, SH and OV are important risk factors for gastric cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, bladder cancer, and cholangiocarcinoma, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase (iNOS) expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in SH-associated bladder cancer tissues, and in Oct3/4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that nitrative and oxidative DNA damage in stem cells may play a key role in infection-related carcinogenesis via chronic inflammation.
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Affiliation(s)
- Shosuke Kawanishi
- Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 Japan
| | - Shiho Ohnishi
- Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 Japan
| | - Ning Ma
- Faculty of Nursing, Suzuka University of Medical Science, Suzuka, Mie 513-8670 Japan
| | - Yusuke Hiraku
- Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 Japan
| | - Shinji Oikawa
- Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 Japan
| | - Mariko Murata
- Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 Japan
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50
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Zibara K, Zeidan A, Bjeije H, Kassem N, Badran B, El-Zein N. ROS mediates interferon gamma induced phosphorylation of Src, through the Raf/ERK pathway, in MCF-7 human breast cancer cell line. J Cell Commun Signal 2016; 11:57-67. [PMID: 27838900 DOI: 10.1007/s12079-016-0362-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 11/03/2016] [Indexed: 01/05/2023] Open
Abstract
Interferon gamma (IFN-ɣ) is a pleiotropic cytokine which plays dual contrasting roles in cancer. Although IFN-ɣ has been clinically used to treat various malignancies, it was recently shown to have protumorigenic activities. Reactive oxygen species (ROS) are overproduced in cancer cells, mainly due to NADPH oxidase activity, which results into several changes in signaling pathways. In this study, we examined IFN-ɣ effect on the phosphorylation levels of key signaling proteins, through ROS production, in the human breast cancer cell line MCF-7. After treatment by IFN-ɣ, results showed a significant increase in the phosphorylation of STAT1, Src, raf, AKT, ERK1/2 and p38 signaling molecules, in a time specific manner. Src and Raf were found to be involved in early stages of IFN-ɣ signaling since their phosphorylation increased very rapidly. Selective inhibition of Src-family kinases resulted in an immediate significant decrease in the phosphorylation status of Raf and ERK1/2, but not p38 and AKT. On the other hand, IFN-ɣ resulted in ROS generation, through H2O2 production, whereas pre-treatment with the ROS inhibitor NAC caused ROS inhibition and a significant decrease in the phosphorylation levels of AKT, ERK1/2, p38 and STAT1. Moreover, pretreatment with a selective NOX1 inhibitor resulted in a significant decrease of AKT phosphorylation. Finally, no direct relationship was found between ROS production and calcium mobilization. In summary, IFN-ɣ signaling in MCF-7 cell line is ROS-dependent and follows the Src/Raf/ERK pathway whereas its signaling through the AKT pathway is highly dependent on NOX1.
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Affiliation(s)
- Kazem Zibara
- ER045, PRASE, DSST, Lebanese University, Beirut, Lebanon.,Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Asad Zeidan
- Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Hassan Bjeije
- ER045, PRASE, DSST, Lebanese University, Beirut, Lebanon
| | - Nouhad Kassem
- ER045, PRASE, DSST, Lebanese University, Beirut, Lebanon
| | - Bassam Badran
- Biochemistry Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Nabil El-Zein
- ER045, PRASE, DSST, Lebanese University, Beirut, Lebanon. .,Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
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