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Jung WJ, Kim HS, Cha KC, Roh YI, An GJ, Cha YS, Kim H, Lee KH, Hwang SO, Kim OH. Early Evaluation of Myeloperoxidase and Delta Neutrophil Indices Is Similar to 48 h Sequential Organ Failure Assessment Score for Predicting Multiple Organ Failure After Trauma. J Clin Med 2025; 14:3447. [PMID: 40429441 PMCID: PMC12111808 DOI: 10.3390/jcm14103447] [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: 04/02/2025] [Revised: 05/04/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Multiple organ failure is the main cause of mortality in severely injured patients who survive the early post-trauma phase. Myeloperoxidase and delta neutrophil indices may serve useful markers for the early diagnosis of an inflammatory condition. We aimed to ascertain the use of these indices for predicting multiple organ failure after a major trauma. Methods: A retrospective study was performed based on a level I trauma center database that included trauma patients with an injury severity score of >15 points. Organ function was evaluated according to the sequential organ failure assessment score within at least 48 h of admission and the myeloperoxidase and delta neutrophil indices, which were measured every morning. Results: A total of 96 patients were included in this study. Compared with the non-multiple-organ-failure group, the multiple organ failure group had similar myeloperoxidase indices but a significantly higher delta neutrophil index. Multivariate logistic regression analysis revealed no significant difference in the predictive power among the post-trauma multiple organ failure models that included various factors, although model 7, which combined the sequential organ failure assessment score and the myeloperoxidase and delta neutrophil indices, tended to have the maximum predictive power. Conclusions: Early delta neutrophil index (DNI) values and the composite model incorporating SOFA, absolute MPXI, and DNI each demonstrated moderate ability to predict multiple organ failure after major trauma. Prospective multicenter studies that include granular treatment variables are warranted to validate these biomarkers and to explore whether their incorporation into real-time decision tools can improve outcomes.
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Affiliation(s)
- Woo Jin Jung
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Hye Sim Kim
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju 26493, Republic of Korea;
| | - Kyoung Chul Cha
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Young-Il Roh
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Gyo Jin An
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Yong Sung Cha
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Hyun Kim
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Kang Hyun Lee
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Sung Oh Hwang
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
| | - Oh Hyun Kim
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (W.J.J.); (K.C.C.); (Y.-I.R.); (G.J.A.); (Y.S.C.); (H.K.); (K.H.L.); (S.O.H.)
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Zhai H, Wei Z, Jing X, Duan C. A Porphyrin-Faced Zn 8L 6 Cage for Selective Oxidation of C(sp 3)-H Bonds and Sulfides. Inorg Chem 2024; 63:14375-14382. [PMID: 39038208 DOI: 10.1021/acs.inorgchem.4c01009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Catalytic oxidation of benzyl C-H bonds and sulfides from fuel oils stands as an attractive proposition in the quest for clean energy, yet their simultaneous oxidation with a singular, economically friendly catalyst is not well established. In this work, the combination of a cobalt(II) porphyrin ligand with 2-pyridinecarboxaldehyde and ZnII yielded a Zn8L6 cage (Co cube). The three-dimensional conjugated structure effectively enhances energy transfer efficiency, enabling the Co cube to show a good ability to activate oxygen under light conditions for photooxidation. Moreover, this catalytic system demonstrates high selectivity for the photocatalytic oxidation of C(sp3)-H bonds and sulfides, employing the Co cube as a single component catalyst, molecular oxygen as the oxidant, and activating oxygen into 1O2 under mild reaction conditions. This provides significant insights for organic synthesis and future design of photocatalysts with complex molecular components.
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Affiliation(s)
- Haoyu Zhai
- School of Chemistry, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China
| | - Zhong Wei
- School of Chemistry, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China
| | - Xu Jing
- School of Chemistry, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China
| | - Chunying Duan
- School of Chemistry, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China
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3
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Yu Z, Chen X, Chen Z, Wang H, Shah SHA, Bai A, Liu T, Xiao D, Hou X, Li Y. BcSRC2 interacts with BcAPX4 to increase ascorbic acid content for responding ABA signaling and drought stress in pak choi. HORTICULTURE RESEARCH 2024; 11:uhae165. [PMID: 39896045 PMCID: PMC11784589 DOI: 10.1093/hr/uhae165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 06/10/2024] [Indexed: 02/04/2025]
Abstract
As a reducing substance, ascorbic acid functioned well in abiotic and biotic stress. However, the regulatory mechanism of drought resistance is rarely known in pak choi. Here we found a gene BcSRC2 containing a C2 domain that responds to ABA signal and drought regulation in pak choi. Silencing of BcSRC2 reduces ascorbic acid content and drought resistance of pak choi. In Arabidopsis, BcSRC2 overexpression promotes ascorbic acid accumulation and increases drought tolerance. Meanwhile, transcriptome analysis between WT and BcSRC2-overexpressing pak choi suggests that ascorbic acid-related genes are regulated. BcSRC2 interacts with BcAPX4 and inhibit APX activity in vitro and in vivo, increasing the ascorbic acid content. We also found that drought stress increases ABA content, which reduces the expression of BcMYB30. BcMYB30 bound to the promoter of BcSRC2 and reduced its expression. Overall, our results suggest that a regulatory module, BcMYB30-BcSRC2-BcAPX4, plays a central role in increasing ascorbic acid content for responding ABA-mediated drought regulation in pak choi.
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Affiliation(s)
- Zhanghong Yu
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaoshan Chen
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Zhongwen Chen
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Haibin Wang
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Sayyed Hamad Ahmad Shah
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Aimei Bai
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Tongkun Liu
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Dong Xiao
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Xilin Hou
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
| | - Ying Li
- National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China
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4
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Yu Y, Liu S, Yang L, Song P, Liu Z, Liu X, Yan X, Dong Q. Roles of reactive oxygen species in inflammation and cancer. MedComm (Beijing) 2024; 5:e519. [PMID: 38576456 PMCID: PMC10993368 DOI: 10.1002/mco2.519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 01/21/2024] [Accepted: 02/23/2024] [Indexed: 04/06/2024] Open
Abstract
Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS-mediated mechanisms for advancing cancer therapy and developing personalized treatments.
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Affiliation(s)
- Yunfei Yu
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Shengzhuo Liu
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Luchen Yang
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Pan Song
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Zhenghuan Liu
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Xiaoyang Liu
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Xin Yan
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Qiang Dong
- Department of UrologyWest China HospitalSichuan UniversityChengduChina
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5
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Murotomi K, Umeno A, Shichiri M, Tanito M, Yoshida Y. Significance of Singlet Oxygen Molecule in Pathologies. Int J Mol Sci 2023; 24:ijms24032739. [PMID: 36769060 PMCID: PMC9917472 DOI: 10.3390/ijms24032739] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/22/2023] [Accepted: 01/26/2023] [Indexed: 02/04/2023] Open
Abstract
Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions in phagocytosis during inflammation. The imbalance of antioxidant enzymes and antioxidant networks with the generation of singlet oxygen increases oxidative stress, resulting in the undesirable oxidation and modification of biomolecules, such as proteins, DNA, and lipids. This review describes the molecular mechanisms of singlet oxygen production in vivo and methods for the evaluation of damage induced by singlet oxygen. The involvement of singlet oxygen in the pathogenesis of skin and eye diseases is also discussed from the biomolecular perspective. We also present our findings on lipid oxidation products derived from singlet oxygen-mediated oxidation in glaucoma, early diabetes patients, and a mouse model of bronchial asthma. Even in these diseases, oxidation products due to singlet oxygen have not been measured clinically. This review discusses their potential as biomarkers for diagnosis. Recent developments in singlet oxygen scavengers such as carotenoids, which can be utilized to prevent the onset and progression of disease, are also described.
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Affiliation(s)
- Kazutoshi Murotomi
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan
| | - Aya Umeno
- Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan
| | - Mototada Shichiri
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda 563-8577, Japan
- Correspondence: ; Tel.: +81-72-751-8234
| | - Masaki Tanito
- Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan
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6
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Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease. Int J Mol Sci 2022; 23:ijms23020774. [PMID: 35054960 PMCID: PMC8775426 DOI: 10.3390/ijms23020774] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.
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7
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Lee H, Shin W, Kim HJ, Kim J. Turn-On Fluorescence Sensing of Oxygen with Dendrimer-Encapsulated Platinum Nanoparticles as Tunable Oxidase Mimics for Spatially Resolved Measurement of Oxygen Gradient in a Human Gut-on-a-Chip. Anal Chem 2021; 93:16123-16132. [PMID: 34807579 DOI: 10.1021/acs.analchem.1c03891] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Turn-on type fluorescence sensing of O2 is considered a promising approach to developing ways to measure O2 in microenvironments with spatially distributed O2 levels. As a class of nanomaterials with a high degree of control over composition and structure, dendrimer-encapsulated nanoparticles (DENs) are promising candidates to mimic biological enzymes. Here, we report a strategy to monitor spatially distributed O2 across a three-dimensional (3D) human intestinal epithelial layer in a gut-on-a-chip in a turn-on fluorescence sensing manner. The strategy is based on the oxidase-mimetic activity of Pt DENs for catalytic oxidation of nonfluorescent Amplex Red to highly fluorescent resorufin in the presence of O2. We synthesized Pt DENs using two different types of dendrimers (i.e., amine-terminated or hydroxyl-terminated generation 6 polyamidoamine (PAMAM) dendrimers) with six different Pt2+/dendrimer ratios (i.e., 55, 200, 220, 550, 880, and 1320). After clarifying the intrinsic oxidase-mimetic activity of Pt DENs, we determined tunable oxidase-mimetic activity of Pt DENs, especially with fine-tuning the ratios of the Pt precursor ions and dendrimers. Particularly, the optimal Pt DENs having a Pt2+/dendrimer ratio of 1320 exhibited an ∼117-fold increase in the oxidase-mimetic activity for catalyzing the aerobic oxidation of Amplex Red to resorufin compared to one having a Pt2+/dendrimer ratio of 200. This study exemplified a simple yet effective approach for spatially resolved imaging of O2 using metal nanoparticle-based oxidase mimics in microphysiological environments like a human gut-on-a-chip.
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Affiliation(s)
- Hyein Lee
- Department of Chemistry, Research Institute for Basic Sciences, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Woojung Shin
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, United States
| | - Hyun Jung Kim
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, United States
| | - Joohoon Kim
- Department of Chemistry, Research Institute for Basic Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.,KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea
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8
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Talaei K, Garan SA, Quintela BDM, Olufsen MS, Cho J, Jahansooz JR, Bhullar PK, Suen EK, Piszker WJ, Martins NRB, Moreira de Paula MA, Dos Santos RW, Lobosco M. A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus. Front Cell Infect Microbiol 2021; 11:711153. [PMID: 34869049 PMCID: PMC8633844 DOI: 10.3389/fcimb.2021.711153] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 10/14/2021] [Indexed: 11/13/2022] Open
Abstract
Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology.
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Affiliation(s)
- Kian Talaei
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States.,Lawrence Berkeley National Laboratory, Berkeley, CA, United States.,Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, United States
| | - Steven A Garan
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States.,Lawrence Berkeley National Laboratory, Berkeley, CA, United States
| | | | - Mette S Olufsen
- Department of Mathematics, North Carolina State University, Raleigh, NC, United States
| | - Joshua Cho
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States.,Lawrence Berkeley National Laboratory, Berkeley, CA, United States.,College of Chemistry, University of California, Berkeley, Berkeley, CA, United States
| | - Julia R Jahansooz
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States.,Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, United States
| | - Puneet K Bhullar
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States.,Mayo Clinic Alix School of Medicine, Scottsdale, AZ, United States
| | - Elliott K Suen
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States.,Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States
| | - Walter J Piszker
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States.,College of Chemistry, University of California, Berkeley, Berkeley, CA, United States
| | - Nuno R B Martins
- Center for Research and Education in Aging, University of California, Berkeley, Berkeley, CA, United States
| | | | | | - Marcelo Lobosco
- Department of Computer Science, Federal University of Juiz de Fora, Juiz de Fora, Brazil
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9
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Trenker S, Grunenberg L, Banerjee T, Savasci G, Poller LM, Muggli KIM, Haase F, Ochsenfeld C, Lotsch BV. A flavin-inspired covalent organic framework for photocatalytic alcohol oxidation. Chem Sci 2021; 12:15143-15150. [PMID: 34909156 PMCID: PMC8612393 DOI: 10.1039/d1sc04143f] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/02/2021] [Indexed: 12/02/2022] Open
Abstract
Covalent organic frameworks (COFs) offer a number of key properties that predestine them to be used as heterogeneous photocatalysts, including intrinsic porosity, long-range order, and light absorption. Since COFs can be constructed from a practically unlimited library of organic building blocks, these properties can be precisely tuned by choosing suitable linkers. Herein, we report the construction and use of a novel COF (FEAx-COF) photocatalyst, inspired by natural flavin cofactors. We show that the functionality of the alloxazine chromophore incorporated into the COF backbone is retained and study the effects of this heterogenization approach by comparison with similar molecular photocatalysts. We find that the integration of alloxazine chromophores into the framework significantly extends the absorption spectrum into the visible range, allowing for photocatalytic oxidation of benzylic alcohols to aldehydes even with low-energy visible light. In addition, the activity of the heterogeneous COF photocatalyst is less dependent on the chosen solvent, making it more versatile compared to molecular alloxazines. Finally, the use of oxygen as the terminal oxidant renders FEAx-COF a promising and “green” heterogeneous photocatalyst. In this manuscript, we report the development of a novel alloxazine COF inspired by naturally occurring flavin cofactors for photoredox catalysis.![]()
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Affiliation(s)
- Stefan Trenker
- Max Planck Institute for Solid State Research Heisenbergstr. 1 70569 Stuttgart Germany .,Department of Chemistry, University of Munich (LMU) Butenandtstr. 5-13 81377 Munich Germany.,Center for Nanoscience Schellingstr. 4 80799 Munich Germany
| | - Lars Grunenberg
- Max Planck Institute for Solid State Research Heisenbergstr. 1 70569 Stuttgart Germany .,Department of Chemistry, University of Munich (LMU) Butenandtstr. 5-13 81377 Munich Germany
| | - Tanmay Banerjee
- Department of Chemistry, Birla Institute of Technology and Science Pilani, Pilani Campus Rajasthan 333031 India
| | - Gökcen Savasci
- Max Planck Institute for Solid State Research Heisenbergstr. 1 70569 Stuttgart Germany .,Department of Chemistry, University of Munich (LMU) Butenandtstr. 5-13 81377 Munich Germany.,Center for Nanoscience Schellingstr. 4 80799 Munich Germany.,Karlsruhe Institute of Technology (KIT), IFG - Institute for Functional Interfaces Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen Germany
| | - Laura M Poller
- Department of Chemistry, University of Munich (LMU) Butenandtstr. 5-13 81377 Munich Germany
| | - Katharina I M Muggli
- Department of Chemistry, University of Munich (LMU) Butenandtstr. 5-13 81377 Munich Germany
| | - Frederik Haase
- Karlsruhe Institute of Technology (KIT), IFG - Institute for Functional Interfaces Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen Germany
| | - Christian Ochsenfeld
- Max Planck Institute for Solid State Research Heisenbergstr. 1 70569 Stuttgart Germany .,Department of Chemistry, University of Munich (LMU) Butenandtstr. 5-13 81377 Munich Germany.,Center for Nanoscience Schellingstr. 4 80799 Munich Germany.,e-conversion Cluster of Excellence Lichtenbergstr. 4a, 85748 Garching Germany
| | - Bettina V Lotsch
- Max Planck Institute for Solid State Research Heisenbergstr. 1 70569 Stuttgart Germany .,Department of Chemistry, University of Munich (LMU) Butenandtstr. 5-13 81377 Munich Germany.,Center for Nanoscience Schellingstr. 4 80799 Munich Germany.,e-conversion Cluster of Excellence Lichtenbergstr. 4a, 85748 Garching Germany
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10
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Stability Performance Analysis of Various Packaging Materials and Coating Strategies for Chronic Neural Implants under Accelerated, Reactive Aging Tests. MICROMACHINES 2020; 11:mi11090810. [PMID: 32858951 PMCID: PMC7570179 DOI: 10.3390/mi11090810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/21/2020] [Accepted: 08/23/2020] [Indexed: 12/13/2022]
Abstract
Reliable packaging for implantable neural prosthetic devices in body fluids is a long-standing challenge for devices’ chronic applications. This work studied the stability of Parylene C (PA), SiO2, and Si3N4 packages and coating strategies on tungsten wires using accelerated, reactive aging tests in three solutions: pH 7.4 phosphate-buffered saline (PBS), PBS + 30 mM H2O2, and PBS + 150 mM H2O2. Different combinations of coating thicknesses and deposition methods were studied at various testing temperatures. Analysis of the preliminary data shows that the pinholes/defects, cracks, and interface delamination are the main attributes of metal erosion and degradation in reactive aging solutions. Failure at the interface of package and metal is the dominating factor in the wire samples with open tips.
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11
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Murotomi K, Umeno A, Sugino S, Yoshida Y. Quantitative kinetics of intracellular singlet oxygen generation using a fluorescence probe. Sci Rep 2020; 10:10616. [PMID: 32606330 PMCID: PMC7327044 DOI: 10.1038/s41598-020-67155-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/29/2020] [Indexed: 11/24/2022] Open
Abstract
Singlet oxygen (1O2) is a type of reactive oxygen species involved in numerous physiological activities. We previously reported that 1O2-specific oxidation products are increased in patients with prediabetes, suggesting that measurement of 1O2 may be an important indicator of physiological and pathological conditions. The turnover in the generation and quenching of 1O2 is extremely rapid during biological activities owing to it high reactivity and short lifetime in solution. However, the dynamic changes in 1O2 generation in living cells have not been fully explored. In this study, we investigated whether the kinetics of 1O2 generation can be quantified using a far-red fluorescent probe for mitochondrial 1O2, Si-DMA, following addition of the 1O2 generator, endoperoxide, to mammalian cells. The kinetics of Si-DMA fluorescence intensity dose-dependently increased following treatment of mammalian living cells with endoperoxide. Alternatively, treatment with 1O2 quenchers decreased the fluorescence intensities following endoperoxide treatment. Our results indicate that the kinetics of intracellular 1O2 can be readily obtained using Si-DMA and time-lapse imaging, which provides new insights into the mechanism of 1O2 generation in mammalian cells and the exploration of 1O2 generators and quenchers.
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Affiliation(s)
- Kazutoshi Murotomi
- Molecular Neurophysiology Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
| | - Aya Umeno
- Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa, 761-0301, Japan
| | - Sakiko Sugino
- Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa, 761-0301, Japan
| | - Yasukazu Yoshida
- LG Japan Lab Inc., Glass Cube Shinagawa 2F, 4-13-14, Higashi Shinagawa, Shinagawa-ku, Tokyo, 140-0002, Japan
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12
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Gu K, Wang Y, Shen J, Zhu J, Zhu Y, Li C. Effective Singlet Oxygen Generation in Silica-Coated CsPbBr 3 Quantum Dots through Energy Transfer for Photocatalysis. CHEMSUSCHEM 2020; 13:682-687. [PMID: 31849186 DOI: 10.1002/cssc.201903157] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 12/17/2019] [Indexed: 06/10/2023]
Abstract
Here, silica-coated CsPbBr3 quantum dots (QDs) were demonstrated to be effective photosensitizers for the generation of singlet oxygen (1 O2 ). The silica encapsulation improved the stability of the perovskite QDs while also preserving an excellent light-harvesting capability in the visible-light region. The appropriate exciton binding energy and dark exciton generation characteristics of perovskite QDs may be responsible for the energy transfer. The high oxidizability of 1 O2 makes the material attractive for application in decomposition of organic dyes such as methyl orange. This work provides new insight for designing excellent perovskite-based photocatalysts.
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Affiliation(s)
- Kailun Gu
- Shanghai Engineering Research Center of Hierarchical Nanomaterials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China
| | - Yu Wang
- Shanghai Engineering Research Center of Hierarchical Nanomaterials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China
| | - Jianhua Shen
- Shanghai Engineering Research Center of Hierarchical Nanomaterials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China
| | - Jingrun Zhu
- Shanghai Engineering Research Center of Hierarchical Nanomaterials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China
| | - Yihua Zhu
- Shanghai Engineering Research Center of Hierarchical Nanomaterials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China
| | - Chunzhong Li
- School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China
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13
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Wang C, Yin H, Bi L, Su J, Zhang M, Lyu T, Cooper M, Pan G. Highly efficient and irreversible removal of cadmium through the formation of a solid solution. JOURNAL OF HAZARDOUS MATERIALS 2020; 384:121461. [PMID: 31685320 DOI: 10.1016/j.jhazmat.2019.121461] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 10/07/2019] [Accepted: 10/10/2019] [Indexed: 06/10/2023]
Abstract
Sulfur-containing materials are very attractive for the efficient decontamination of some heavy metals. However, the effective and irreversible removal of Cd2+, coupled with a high uptake efficiency, remains a great challenge due to the relatively low bond dissociation energy of CdS. Herein, we propose a new strategy to overcome this challenge, by the incorporation of Cd2+ into a stable ZnxCd1-xS solid solution, rather than into CdS. This can be realised through the adsorption of Cd2+ by ZnS nanoparticles, which have exhibited a Cd2+ uptake capacity of approximate 400 mg g-1. Through this adsorption mechanism, the Cd2+ concentration in a contaminated solution could effectively be reduced from 50 ppb to <3 ppb, a WHO limit acceptable for drinking water. In addition, ZnS continued to exhibit this noteworthy uptake capacity even in the presence of Cu2+, Pb2+, and Hg2+. ZnS displayed high chemical stability. Particles aged in air for 3 months still retained a> 80% uptake capacity for Cd2+, compared with only 9% uptake capacity for similarly-aged FeS particles. This work reveals a new mechanism for Cd2+ removal with ZnS and establishes a valuable starting point for further studies into the formation of solid solutions for hazardous heavy metal removal applications.
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Affiliation(s)
- Chen Wang
- Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Haidian District, Beijing, 100085, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China
| | - Hui Yin
- Key Laboratory of Arable Land Conservation (Middle and Lower Reaches of Yangtze River), Ministry of Agriculture and Rural Affairs, College of Resources and Environment, Huazhong Agricultural University, Wuhan, 430070, PR China
| | - Lei Bi
- Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Haidian District, Beijing, 100085, PR China.
| | - Jing Su
- Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Haidian District, Beijing, 100085, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China
| | - Meiyi Zhang
- Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Haidian District, Beijing, 100085, PR China
| | - Tao Lyu
- School of Animal, Rural, and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, NG25 0QF, UK; Centre of Integrated Water-Energy-Food Studies (iWEF), School of Animal, Rural, and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, NG25 0QF, UK
| | - Mick Cooper
- School of Animal, Rural, and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, NG25 0QF, UK; Centre of Integrated Water-Energy-Food Studies (iWEF), School of Animal, Rural, and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, NG25 0QF, UK
| | - Gang Pan
- Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Haidian District, Beijing, 100085, PR China; School of Animal, Rural, and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, NG25 0QF, UK; Centre of Integrated Water-Energy-Food Studies (iWEF), School of Animal, Rural, and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, NG25 0QF, UK; Beijing Advanced Science and Innovation Center of CAS, Chinese Academy of Sciences, Beijing, PR China.
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14
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A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity. ACTA ACUST UNITED AC 2020; 28:119-130. [PMID: 31902097 DOI: 10.1007/s40199-019-00323-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 12/17/2019] [Indexed: 12/29/2022]
Abstract
PURPOSE The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. METHODS Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmission-aggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. RESULTS Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. CONCLUSIONS SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. Graphical abstract .
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Fu SS, Ren XY, Guo S, Lan G, Zhang ZM, Lu TB, Lin W. Synergistic Effect over Sub-nm Pt Nanocluster@MOFs Significantly Boosts Photo-oxidation of N-alkyl(iso)quinolinium Salts. iScience 2019; 23:100793. [PMID: 31958757 PMCID: PMC6992937 DOI: 10.1016/j.isci.2019.100793] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 12/10/2019] [Accepted: 12/18/2019] [Indexed: 11/17/2022] Open
Abstract
Quinolones and isoquinolones are of interest to pharmaceutical industry owing to their potent biological activities. Herein, we first encapsulated sub-nm Pt nanoclusters into Zr-porphyrin frameworks to afford an efficient photocatalyst Pt0.9@PCN-221. This catalyst can dramatically promote electron-hole separation and 1O2 generation to achieve synergistic effect first in the metal-organic framework (MOF) system, leading to the highest activity in photosynthesis of (iso)quinolones in >90.0% yields without any electronic sacrificial agents. Impressively, Pt0.9@PCN-221 was reused 10 times without loss of activity and can catalyze gram-scale synthesis of 1-methyl-5-nitroisoquinolinone at an activity of 175.8 g·gcat−1, 22 times higher than that of PCN-221. Systematic investigations reveal the contribution of synergistic effect of photogenerated electron, photogenerated hole, and 1O2 generation for efficient photo-oxidation, thus highlighting a new strategy to integrate multiple functional components into MOFs to synergistically catalyze complex photoreactions for exploring biologically active heterocyclic molecules.
A state-of-the-art photocatalyst for preparation of bioactive (iso)quinolones Synergistic catalysis of photogenerated e−/h+ and 1O2 Sub-nm Pt0.9@PCN-221 with a high efficiency of e−-h+ separation and 1O2 generation
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Affiliation(s)
- Shan-Shan Fu
- Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China
| | - Xiu-Ying Ren
- College of Chemistry, Northeast Normal University, Changchun 130024, P.R. China
| | - Song Guo
- Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China.
| | - Guangxu Lan
- Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA
| | - Zhi-Ming Zhang
- Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China; College of Chemistry, Northeast Normal University, Changchun 130024, P.R. China.
| | - Tong-Bu Lu
- Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China
| | - Wenbin Lin
- Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA
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16
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Role of mitochondria in rescuing glycolytically inhibited subpopulation of triple negative but not hormone-responsive breast cancer cells. Sci Rep 2019; 9:13748. [PMID: 31551501 PMCID: PMC6760198 DOI: 10.1038/s41598-019-50141-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 09/06/2019] [Indexed: 12/26/2022] Open
Abstract
Triple-negative breast cancer (TNBC) subtype is among the most aggressive cancers with the worst prognosis and least therapeutic targetability while being more likely to spread and recur. Cancer transformations profoundly alter cellular metabolism by increasing glucose consumption via glycolysis to support tumorigenesis. Here we confirm that relative to ER-positive cells (MCF7), TNBC cells (MBA-MD-231) rely more on glycolysis thus providing a rationale to target these cells with glycolytic inhibitors. Indeed, iodoacetate (IA), an effective GAPDH inhibitor, caused about 70% drop in MDA-MB-231 cell viability at 20 μM while 40 μM IA was needed to decrease MCF7 cell viability only by 30% within 4 hours of treatment. However, the triple negative cells showed strong ability to recover after 24 h whereas MCF7 cells were completely eliminated at concentrations <10 μM. To understand the mechanism of MDA-MB-231 cell survival, we studied metabolic modulations associated with acute and extended treatment with IA. The resilient TNBC cell population showed a significantly greater count of cells with active mitochondria, lower apoptotic markers, normal cell cycle regulations, moderately lowered ROS, but increased mRNA levels of p27 and PARP1; all compatible with enhanced cell survival. Our results highlight an interplay between PARP and mitochondrial oxidative phosphorylation in TNBC that comes into play in response to glycolytic disruption. In the light of these findings, we suggest that combined treatment with PARP and mitochondrial inhibitors may provide novel therapeutic strategy against TNBC.
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17
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Bauer G. The synergistic effect between hydrogen peroxide and nitrite, two long-lived molecular species from cold atmospheric plasma, triggers tumor cells to induce their own cell death. Redox Biol 2019; 26:101291. [PMID: 31421409 PMCID: PMC6831866 DOI: 10.1016/j.redox.2019.101291] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 07/28/2019] [Accepted: 08/05/2019] [Indexed: 12/14/2022] Open
Abstract
Nitrite and H2O2 are long-lived species in cold atmospheric plasma and plasma-activated medium. It is known that their synergistic interaction is required for selective apoptosis induction in tumor cells that are treated with plasma-activated medium. This study shows that the interaction between nitrite and H2O2 leads to the formation of peroxynitrite, followed by singlet oxygen generation through the interaction between peroxynitrite and residual H2O2. This primary singlet oxygen causes local inactivation of few catalase molecules on the surface of tumor cells. As a consequence, H2O2 and peroxynitrite that are constantly produced by tumor cells and are usually decomposed by their protective membrane-associated catalase, are surviving at the site of locally inactivated catalase. This leads to the generation of secondary singlet oxygen through the interaction between tumor cell-derived H2O2 and peroxynitrite. This selfsustained process leads to autoamplification of secondary singlet oxygen generation and catalase inactivation. Inactivation of catalase allows the influx of H2O2 through aquaporins, leading to intracellular glutathione depletion and sensitization of the cells for apoptosis induction through lipid peroxidation. It also allows to establish intercellular apoptosis-inducing HOCl signaling, driven by active NOX1 and finalized by lipid peroxidation through hydroxyl radicals that activates the mitochondrial pathway of apoptosis. This experimentally established model is based on a triggering function of CAP and PAM-derived H2O2/nitrite that causes selective cell death in tumor cells based on their own ROS and RNS. This model explains the selectivity of CAP and PAM action towards tumor cells and is in contradiction to previous models that implicated that ROS/RNS from CAP or PAM were sufficient to directly cause cell death of tumor cells.
H2O2 and nitrite generate peroxynitrite, followed by primary singlet oxygen formation. Primary singlet oxygen causes local inactivation of tumor cell protective catalase. Amplificatory generation of secondary singlet oxygen and catalase inactivation are established. Inactivation of catalase allows aquaporin-mediated influx of H2O2 and glutathione depletion. In this way, CAP and PAM trigger tumor cells to contribute to their own cell death.
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Affiliation(s)
- Georg Bauer
- Institute of Virology, Medical Center, University of Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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18
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Huo HJ, Chen SN, Li L, Nie P. Functional characterization of IL-10 and its receptor subunits in a perciform fish, the mandarin fish, Siniperca chuatsi. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2019; 97:64-75. [PMID: 30935989 DOI: 10.1016/j.dci.2019.03.017] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 03/26/2019] [Accepted: 03/26/2019] [Indexed: 06/09/2023]
Abstract
Interleukin (IL)-10 is an immune-regulatory cytokine with multiple functions. In the current study, IL-10 and its two receptors, IL-10R1 and IL-10R2 were identified in mandarin fish, Siniperca chuatsi. The inhibitory effect of mandarin fish IL-10 was investigated on pro-inflammatory cytokine expression and the ligand-receptor relationship. This IL-10 possesses conserved cysteine residues, predicted α-helices and a typical IL-10 family signature motif, similar to its mammalian orthologue, and IL-10R1 harbours predicted JAK1 and STAT3 binding sites in the intracellular region. The fish IL-10 and IL-10R1 exhibit high expression levels in several immune-related organs/tissues, such as spleen, trunk kidney and head kidney, and IL-10R2 possesses a constitutive expression pattern. The expression of IL-10 shows significant increase in spleen from infectious spleen and kidney necrosis virus (ISKNV) infected mandarin fish, where the two receptors also exhibit different levels of induced expression. Mandarin fish IL-10 also exhibits significant response to the stimulation of LPS, PHA and PMA, with the two receptors exhibiting an interesting decrease in expression following the treatment of PMA. The pro-inflammatory cytokines, IL-6, IL-1β, IL-8, TNF-α, show diminished up-regulation in LPS-stimulated splenocytes pre-incubated with IL-10, indicating the anti-inflammatory roles of mandarin fish IL-10. In EPC cells transfected with different combinations of receptors, IL-10 can enhance the expression of suppressor of cytokine signalling 3 (SOCS3) only when IL-10R1 and IL-10R2 are both expressed, suggesting the participation of the two receptors in signal transduction of mandarin fish IL-10. Similar results are observed with the usage of chimeric receptors, IL-10R1/CRFB1 and IL-10R2/CRFB5. Overall, mandarin fish IL-10 shares conserved ligand-receptor system and the prototypical inhibitory activities on pro-inflammatory cytokine expression with mammalian IL-10, implying the evolutionary conservation of this cytokine.
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Affiliation(s)
- Hui Jun Huo
- State Key Laboratory of Freshwater Ecology and Biotechnology, and Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Shan Nan Chen
- State Key Laboratory of Freshwater Ecology and Biotechnology, and Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China
| | - Li Li
- State Key Laboratory of Freshwater Ecology and Biotechnology, and Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China
| | - Pin Nie
- State Key Laboratory of Freshwater Ecology and Biotechnology, and Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, Shandong Province, 266237, China; School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, Shandong Province, 266109, China.
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Kay J, Thadhani E, Samson L, Engelward B. Inflammation-induced DNA damage, mutations and cancer. DNA Repair (Amst) 2019; 83:102673. [PMID: 31387777 DOI: 10.1016/j.dnarep.2019.102673] [Citation(s) in RCA: 264] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 06/15/2019] [Accepted: 07/18/2019] [Indexed: 12/22/2022]
Abstract
The relationships between inflammation and cancer are varied and complex. An important connection linking inflammation to cancer development is DNA damage. During inflammation reactive oxygen and nitrogen species (RONS) are created to combat pathogens and to stimulate tissue repair and regeneration, but these chemicals can also damage DNA, which in turn can promote mutations that initiate and promote cancer. DNA repair pathways are essential for preventing DNA damage from causing mutations and cytotoxicity, but RONS can interfere with repair mechanisms, reducing their efficacy. Further, cellular responses to DNA damage, such as damage signaling and cytotoxicity, can promote inflammation, creating a positive feedback loop. Despite coordination of DNA repair and oxidative stress responses, there are nevertheless examples whereby inflammation has been shown to promote mutagenesis, tissue damage, and ultimately carcinogenesis. Here, we discuss the DNA damage-mediated associations between inflammation, mutagenesis and cancer.
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Affiliation(s)
- Jennifer Kay
- Department of Biological Engineering, United States.
| | | | - Leona Samson
- Department of Biological Engineering, United States; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, United States
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Wu X, Dai H, Xu C, Liu L, Li S. Citric acid modification of a polymer exhibits antioxidant and anti‐inflammatory properties in stem cells and tissues. J Biomed Mater Res A 2019; 107:2414-2424. [DOI: 10.1002/jbm.a.36748] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 05/19/2019] [Accepted: 05/27/2019] [Indexed: 12/27/2022]
Affiliation(s)
- Xiaopei Wu
- State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of Technology Wuhan China
| | - Honglian Dai
- State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of Technology Wuhan China
- Biomedical Materials and Engineering Research Center of Hubei Province Wuhan China
| | - Chao Xu
- State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of Technology Wuhan China
| | - Langlang Liu
- State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of Technology Wuhan China
| | - Shipu Li
- State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of Technology Wuhan China
- Biomedical Materials and Engineering Research Center of Hubei Province Wuhan China
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Accuracy of neutrophil CD64 expression in diagnosing infection in patients with autoimmune diseases: a meta-analysis. Clin Rheumatol 2019; 38:1319-1328. [PMID: 30915651 DOI: 10.1007/s10067-019-04518-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 03/09/2019] [Accepted: 03/13/2019] [Indexed: 12/23/2022]
Abstract
We aimed to systematically evaluate the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases. Studies were searched in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases up to October 2018. There was no restriction for language and age. Prospective studies examining the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of eligible studies. Stata 15.1 and Meta-DiSc 1.4 software were used for data analysis. Eleven studies fulfilled the inclusion criteria (677 patients, 229 patients with bacterial infection, and 448 without infection). The pooled sensitivity and specificity of nCD64 were 89% (95% confidence interval (CI) 82-93) and 94% (95% CI 91-96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 14.9 (95% CI 9.3-23.8) and 0.12 (95% CI 0.07-0.20), respectively. The diagnostic odds ratio and area under the summary receiver operating characteristic curve were 123 (95% CI 53-283) and 0.97 (95% CI 0.95-0.98), respectively. The univariate meta-regression analysis showed that region, type of disease, antibiotic therapy, and presentation of nCD64 measurement results were responsible for the heterogeneity. The Deeks' funnel plot asymmetry test showed that there was no publication bias (p = 0.15). nCD64 has a good overall diagnostic performance for differentiating infection from disease flare in patients with autoimmune diseases. Further studies are needed to confirm the optimized cutoff value.
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22
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Comprehensive measurements of hydroxylinoleate and hydroxyarachidonate isomers in blood samples from primary open-angle glaucoma patients and controls. Sci Rep 2019; 9:2171. [PMID: 30778084 PMCID: PMC6379359 DOI: 10.1038/s41598-018-36952-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 11/27/2018] [Indexed: 12/12/2022] Open
Abstract
We previously reported that lower systemic antioxidant capacity is involved in primary open-angle glaucoma (POAG) and exfoliation syndrome pathogeneses as measured by ferric-reducing activity. In the present study, we measured hydroxylinoleate (HODE) and hydroxyarachidonate (HETE) isomer serum levels after sample reduction and saponification to investigate POAG pathogenesis. POAG patients (n = 198) were recruited and divided into normal- and high-tension glaucoma groups (n = 84 and 114, respectively) depending on intraocular pressure. Total HODE (/linoleic acid) and HETE (/arachidonic acid) serum levels were significantly higher in the POAG group (211.9 ± 143.0 and 181.0 ± 164.1 µmol/mol, respectively) than in controls (167.1 ± 105.2 and 132.5 ± 139.7 µmol/mol, p = 0.0025 and 0.0101, respectively). The associations between HODEs/HETEs and glaucoma were further confirmed by multivariate analyses after adjusting for differences in demographic parameters. Among the HODE isomers, the levels of 9- and 13-(Z,E)-HODEs (p = 0.0014) and singlet oxygen-specific products (i.e., 10- and 12-(Z,E)-HODEs, p = 0.0345) were higher in the POAG group than in controls, while free radical-mediated oxidation-specific products (i.e., 9- and 13-(E,E)-HODEs, p = 0.0557) demonstrated a marginal difference. Enzymatic and singlet oxygen-mediated fatty acid oxidation may be major pathways of oxidation process in glaucoma subjects.
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Advances in Penetrating Multichannel Microelectrodes Based on the Utah Array Platform. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1101:1-40. [PMID: 31729670 DOI: 10.1007/978-981-13-2050-7_1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The Utah electrode array (UEA) and its many derivatives have become a gold standard for high-channel count bi-directional neural interfaces, in particular in human subject applications. The chapter provides a brief overview of leading electrode concepts and the context in which the UEA has to be understood. It goes on to discuss the key advances and developments of the UEA platform in the past 15 years, as well as novel wireless and system integration technologies that will merge into future generations of fully integrated devices. Aspects covered include novel device architectures that allow scaling of channel count and density of electrode contacts, material improvements to substrate, electrode contacts, and encapsulation. Further subjects are adaptations of the UEA platform to support IR and optogenetic simulation as well as an improved understanding of failure modes and methods to test and accelerate degradation in vitro such as to better predict device failure and lifetime in vivo.
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Citrate reduced oxidative damage in stem cells by regulating cellular redox signaling pathways and represent a potential treatment for oxidative stress-induced diseases. Redox Biol 2018; 21:101057. [PMID: 30576924 PMCID: PMC6302140 DOI: 10.1016/j.redox.2018.11.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 11/14/2018] [Accepted: 11/21/2018] [Indexed: 02/07/2023] Open
Abstract
Chemical substances containing citrate such as calcium citrate, citrate esters and citric acid exhibit anti-oxidant and anti-inflammatory properties in different cells and tissues. However, data on the anti-oxidant and anti-inflammatory properties and mechanisms of action of citrate are insufficient. In this study, we systematically evaluated the anti-oxidant capacity of citrate using chemical, cellular and animal assays. Citrate showed a stable molecular structure and did not directly react with oxides. Citrate exerted protective and anti-apoptotic effects on BMSCs and also showed significant inhibitory effects on the oxidative stress and inflammatory reactions in the rat air pouch model. By using proteomics, we found that PPARγ contributed to the upregulation of various free radical scavenging proteins and the downregulation of diverse components of the inflammatory responses. Citrate-regulated global PPARγ expression was evidenced by the significant increase expression of PPARγ in PC12 cell line. Our results provide novel insights into the role of citrate in regulating cellular redox signaling and the function of PPARγ signaling in this process and also provide basic molecular cell biology information to improve the applications of biomaterials or stem cells as treatments for oxidative stress-induced degenerative diseases and inflammatory diseases.
Citrate exerts anti-oxidant and anti-inflammatory properties in BMSCs and tissues. Citrate can upregulate and downregulate anti-oxidant and anti-inflammatory proteins in BMSCs. Citrate can regulate anti-oxidant and anti-inflammatory proteins via PPARγ dependent and independent pathways.
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Kim SK, Rho SJ, Kim SH, Kim SY, Song SH, Yoo JY, Kim CH, Lee SH. Protective effects of diphenyleneiodonium, an NADPH oxidase inhibitor, on lipopolysaccharide-induced acute lung injury. Clin Exp Pharmacol Physiol 2018; 46:153-162. [PMID: 30403294 DOI: 10.1111/1440-1681.13050] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 10/29/2018] [Accepted: 10/31/2018] [Indexed: 11/29/2022]
Abstract
NADPH oxidase (NOX) plays an important role in inflammatory response by producing reactive oxygen species (ROS). The inhibition of NOX has been shown to induce anti-inflammatory effects in a few experimental models. The aim of this study was to investigate the effects of diphenyleneiodonium (DPI), a NOX inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a rat model. Sprague-Dawley rats were intraperitoneally administered by DPI (5 mg/kg) 30 minutes after intratracheal instillation of LPS (3 mg/kg). After 6 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The NOX activity in lung tissue was significantly increased in LPS-treated rats. It was significantly attenuated by DPI. DPI-treated rats showed significant reduction in the intracellular ROS, the number of inflammatory cells, and cytokines (TNF-α and IL-6) in BALF compared with LPS-treated rats. In lung tissue, DPI-treated rats showed significantly decreased malondialdehyde content and increased activity of glutathione peroxidase and superoxide dismutase compared with LPS-treated rats. Lung injury score, myeloperoxidase activity, and inducible nitric oxide synthase expression were significantly decreased in DPI-treated rats compared with LPS-treated animals. Western blotting analysis demonstrated that DPI significantly suppressed LPS-induced activation of NF-κB and ERK1/2 and SAPK/JNK in MAPK pathway. Our results suggest that DPI may have protective effects on LPS-induced ALI thorough anti-oxidative and anti-inflammatory effects which may be due to inactivation of the NF-κB, ERK1/2, and SAPK/JNK pathway. These results suggest the therapeutic potential of DPI as an anti-inflammatory agent in ALI.
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Affiliation(s)
- Sung Kyoung Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Seung Joon Rho
- Research Institute of Medical Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Seung Hoon Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Shin Young Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - So Hyang Song
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Jin Young Yoo
- Department of Pathology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Chi Hong Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Sang Haak Lee
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
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Hyperbaric Oxygen Therapy and Utilization in Infectious Disease. CURRENT EMERGENCY AND HOSPITAL MEDICINE REPORTS 2018. [DOI: 10.1007/s40138-018-0166-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Kuliasha CA, Judy JW. in vitro Reactive-Accelerated-Aging (RAA) Assessment of Tissue-Engineered Electronic Nerve Interfaces (TEENI). ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2018; 2018:5061-5064. [PMID: 30441478 PMCID: PMC8059780 DOI: 10.1109/embc.2018.8513458] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
A reactive-accelerated-aging (RAA) soak-test has been employed to challenge microfabricated neural interface devices against an aggressive environment that mimics worstcase chronic physiological inflammation. The RAA tests were able to determine the ability of different materials to increase the adhesive strength of the polyimide and platinum-goldplatinum metallization thin-film interface. It was found that a 3-day RAA soak-test at 87 °C in phosphate buffered saline with 10 to 20 mM hydrogen peroxide resulted in adhesive failure of the metal-polyimide interface when titanium was used as the primary adhesion promotor. The addition of hydrogenated amorphous silicon carbide was able to eliminate the onset of adhesive failure of the metal-polyimide interface during 7-day RAA soak tests. However, sporadic cracking of the silicon carbide layer resulted in a minority of broken metal interconnects that resulted in failed electrodes. These tests have demonstrated the ability of RAA soak tests to provide rapid in vitro assessment of microfabricated neural interfaces and thereby reduce the time needed to develop synthetic methods to fabricate chronically reliable devices.
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Afolayan FI, Erinwusi B, Oyeyemi OT. Immunomodulatory activity of curcumin-entrapped poly d,l-lactic- co-glycolic acid nanoparticles in mice. Integr Med Res 2018; 7:168-175. [PMID: 29989030 PMCID: PMC6035456 DOI: 10.1016/j.imr.2018.02.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Revised: 02/01/2018] [Accepted: 02/14/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Studies have shown that curcumin from Curcuma longa has a wide range of medicinal and immunomodulatory properties. These activities have, however, been hindered by its low bioavailability. Meanwhile, incorporation of nanoparticles has been shown to increase bioavailability of certain drugs. This study was, therefore, conducted to comparatively evaluate the immunomodulatory activity of free and nanoparticulate curcumin in mice. METHODS Healthy albino mice were sensitized with sheep red blood cells (SRBCs) and thereafter free and nanoparticulate curcumin were administered orally at doses of 5 mg/kg/day and 10 mg/kg/day for 10 days to the mice. The assessment of the immunomodulatory activity was carried out by determining the humoral and cell-mediated immune responses using hemagglutination and delayed-type hypersensitivity assays, respectively. Hematological components and some lymphoid organs of treated mice were further evaluated. RESULTS The study showed that nanoparticulate curcumin stimulated higher early cell-mediated immune response at 5 mg/kg and 10 mg/kg when compared to control. While nanoparticulate curcumin significantly stimulated primary humoral immune response with 9.00 ± 1.00 antibody titre (p < 0.05), the free curcumin suppressed the immunity with 3.33 ± 0.67 antibody titre when compared to control. Similar result was observed with secondary humoral antibody titres. Production of white blood cells and weight of the lymphoid organs were also enhanced in the groups that received 10 mg/kg nanocurcumin. CONCLUSION This work showed that poly d,l-lactic-co-glycolic acid entrapped curcumin nanoparticle could increase bioavailability of curcumin for improved immunity.
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Affiliation(s)
- Funmilayo I.D. Afolayan
- Cell Biology and Genetics Unit, Department of Zoology, University of Ibadan, Ibadan, Nigeria
| | - Blessing Erinwusi
- Cell Biology and Genetics Unit, Department of Zoology, University of Ibadan, Ibadan, Nigeria
| | - Oyetunde T. Oyeyemi
- Department of Biological Sciences, University of Medical Sciences, Ondo, Nigeria
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Thomason HA, Lovett JM, Spina CJ, Stephenson C, McBain AJ, Hardman MJ. Silver oxysalts promote cutaneous wound healing independent of infection. Wound Repair Regen 2018. [DOI: 10.1111/wrr.12627] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Helen A. Thomason
- Crawford Healthcare Ltd.; Knutsford Cheshire United Kingdom
- Faculty of Biology, Medicine and Health; The University of Manchester; Manchester United Kingdom
| | | | | | | | - Andrew J. McBain
- Faculty of Biology, Medicine and Health; The University of Manchester; Manchester United Kingdom
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31
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Hassoun EA, Zeng X. Comparative toxicity studies on bromochloroacetate, dibromoacetate, and bromodichloroacetate in J774A.1 macrophages: Roles of superoxide anion and protein carbonyl compounds. J Biochem Mol Toxicol 2018; 32:e22045. [PMID: 29457867 DOI: 10.1002/jbt.22045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 01/16/2018] [Accepted: 01/20/2018] [Indexed: 11/09/2022]
Abstract
The brominated and mixed bromo-chloro-haloacetates, such as dibromoacetate (DBA), bromochloroacetate (BCA), and bromodichloroacetate (BDCA), are by-products of water chlorination and are found at lower levels than the fully chlorinated acetates in the drinking water. The toxicities of the compounds were assessed in J774A.1 cells and were found to induce concentration-dependent increases in cell death and superoxide anion and protein carbonyl compounds production. Compared to the previously tested concentrations of dichoroacetate (DCA) and trichloroacetate (TCA) in the same cell line, the tested haloacetates induced similar effects on cellular viability and superoxide anion production but at DBA and BCA concentrations that were approximately 40-160 times lower than those of DCA and TCA, and at BDCA concentrations that were 4-16 times lower than those of DCA and TCA. Also, production of super oxide anion, protein carbonyl compounds, and induction of phagocytic activation are suggested to play a role in their toxicity.
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Affiliation(s)
- Ezdihar A Hassoun
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo Health Science Campus, Toledo, OH, 43614, USA
| | - Xiaoqun Zeng
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo Health Science Campus, Toledo, OH, 43614, USA
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Umeno A, Fukui T, Hashimoto Y, Kataoka M, Hagihara Y, Nagai H, Horie M, Shichiri M, Yoshino K, Yoshida Y. Early diagnosis of type 2 diabetes based on multiple biomarkers and non-invasive indices. J Clin Biochem Nutr 2017; 62:187-194. [PMID: 29610560 PMCID: PMC5874237 DOI: 10.3164/jcbn.17-81] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Accepted: 09/05/2017] [Indexed: 01/23/2023] Open
Abstract
We previously reported that type 2 diabetes risk, early impaired glucose tolerance and insulin resistance can be predicted by measuring the fasting levels of certain biomarkers. Here we validated these findings in randomly recruited healthy volunteers (n = 101) based on biomarker expression as well as various non-invasive indices. Weight, body mass index, waist circumference and visceral fat differed between individuals with impaired fasting glucose and/or impaired glucose tolerance, and normal subjects. Fasting plasma levels of glycated hemoglobin, leptin, pro-insulin and retinol binding protein 4 differed between impaired fasting glucose/impaired glucose tolerance and normal subjects group and between newly detected diabetes and normal subjects group. Insulin resistance was correlated with fasting levels of insulin and leptin/adiponectin (r = 0.913); of insulin, retinol binding protein 4 and leptin/adiponectin (r = 0.903); and of insulin, glycated albumin, and leptin/adiponectin (r = 0.913). Type 2 diabetes risk, early impaired glucose tolerance and insulin resistance were predicted with >98% specificity and sensitivity by comparing fasting glucose levels to the estimated Matsuda Index based on fasting levels of insulin, adiponectin and leptin with or without oxidative lineolate metabolites. Non-invasive indices are slightly correlated with glucose tolerance and insulin resistance but do not increase the accuracy of predicting type 2 diabetes risk.
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Affiliation(s)
- Aya Umeno
- Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
| | - Toshiki Fukui
- Olive Takamatsu Medical Clinic. 649-8 Kankou-cho, Takamatsu, Kagawa 760-0076, Japan
| | - Yoshiko Hashimoto
- Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
| | - Masatoshi Kataoka
- Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
| | - Yoshihisa Hagihara
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka. Ikeda, Osaka 563-8577, Japan
| | - Hidenori Nagai
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka. Ikeda, Osaka 563-8577, Japan
| | - Masanori Horie
- Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
| | - Mototada Shichiri
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka. Ikeda, Osaka 563-8577, Japan
| | - Kohzoh Yoshino
- School of Science and Technology, Kwansei Gakuin University, 2-1 Shigakuen, Sanda, Hyogo 669-1337, Japan
| | - Yasukazu Yoshida
- Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan
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Vomero M, Castagnola E, Ordonez JS, Carli S, Zucchini E, Maggiolini E, Gueli C, Goshi N, Ciarpella F, Cea C, Fadiga L, Ricci D, Kassegne S, Stieglitz T. Incorporation of Silicon Carbide and Diamond‐Like Carbon as Adhesion Promoters Improves In Vitro and In Vivo Stability of Thin‐Film Glassy Carbon Electrocorticography Arrays. ACTA ACUST UNITED AC 2017. [DOI: 10.1002/adbi.201700081] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Maria Vomero
- Institute of Microsystem Technology (IMTEK) Laboratory for Biomedical Microtechnology Georges‐Koehler‐Allee 102 D‐79110 Freiburg Germany
- Cluster of Excellence BrainLinks‐BrainTools Georges‐Koehler‐Allee 80 79110 Freiburg Germany
| | - Elisa Castagnola
- MEMS Research Laboratory Department of Mechanical Engineering College of Engineering San Diego State University 5500 Campanile Drive San Diego CA 92182‐1323 USA
- Center for Sensorimotor Neural Engineering (CSNE) Box 37, 1414 NE 42nd St., Suite 204 Seattle WA 98105–6271 USA
| | - Juan S. Ordonez
- Institute of Microsystem Technology (IMTEK) Laboratory for Biomedical Microtechnology Georges‐Koehler‐Allee 102 D‐79110 Freiburg Germany
| | - Stefano Carli
- Center for Translational Neurophysiology of Speech and Communication Istituto Italiano di Tecnologia Via Fossato di Mortara 17/19 44121 Ferrara Italy
| | - Elena Zucchini
- Center for Translational Neurophysiology of Speech and Communication Istituto Italiano di Tecnologia Via Fossato di Mortara 17/19 44121 Ferrara Italy
| | - Emma Maggiolini
- Center for Translational Neurophysiology of Speech and Communication Istituto Italiano di Tecnologia Via Fossato di Mortara 17/19 44121 Ferrara Italy
| | - Calogero Gueli
- Institute of Microsystem Technology (IMTEK) Laboratory for Biomedical Microtechnology Georges‐Koehler‐Allee 102 D‐79110 Freiburg Germany
| | - Noah Goshi
- MEMS Research Laboratory Department of Mechanical Engineering College of Engineering San Diego State University 5500 Campanile Drive San Diego CA 92182‐1323 USA
- Center for Sensorimotor Neural Engineering (CSNE) Box 37, 1414 NE 42nd St., Suite 204 Seattle WA 98105–6271 USA
| | - Francesca Ciarpella
- Center for Translational Neurophysiology of Speech and Communication Istituto Italiano di Tecnologia Via Fossato di Mortara 17/19 44121 Ferrara Italy
| | - Claudia Cea
- MEMS Research Laboratory Department of Mechanical Engineering College of Engineering San Diego State University 5500 Campanile Drive San Diego CA 92182‐1323 USA
- Center for Sensorimotor Neural Engineering (CSNE) Box 37, 1414 NE 42nd St., Suite 204 Seattle WA 98105–6271 USA
| | - Luciano Fadiga
- Center for Translational Neurophysiology of Speech and Communication Istituto Italiano di Tecnologia Via Fossato di Mortara 17/19 44121 Ferrara Italy
- Section of Human Physiology University of Ferrara Via Fossato di Mortara 17/19 44121 Ferrara Italy
| | - Davide Ricci
- Center for Translational Neurophysiology of Speech and Communication Istituto Italiano di Tecnologia Via Fossato di Mortara 17/19 44121 Ferrara Italy
| | - Sam Kassegne
- MEMS Research Laboratory Department of Mechanical Engineering College of Engineering San Diego State University 5500 Campanile Drive San Diego CA 92182‐1323 USA
- Center for Sensorimotor Neural Engineering (CSNE) Box 37, 1414 NE 42nd St., Suite 204 Seattle WA 98105–6271 USA
| | - Thomas Stieglitz
- Institute of Microsystem Technology (IMTEK) Laboratory for Biomedical Microtechnology Georges‐Koehler‐Allee 102 D‐79110 Freiburg Germany
- Cluster of Excellence BrainLinks‐BrainTools Georges‐Koehler‐Allee 80 79110 Freiburg Germany
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Bauer G. Autoamplificatory singlet oxygen generation sensitizes tumor cells for intercellular apoptosis-inducing signaling. Mech Ageing Dev 2017; 172:59-77. [PMID: 29137940 DOI: 10.1016/j.mad.2017.11.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 09/01/2017] [Accepted: 11/01/2017] [Indexed: 11/16/2022]
Abstract
Tumor cells express NADPH oxidase-1 (NOX1) in their membrane and control NOX1-based intercellular reactive oxygen and nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling through membrane-associated catalase and superoxide dismutase. TREATMENT of tumor cells with high concentrations of H2O2, peroxnitrite, HOCl, or increasing the concentration of cell-derived NO causes initial generation of singlet oxygen and local inactivation of membrane-associated catalase. As a result, free peroxynitrite and H2O2 interact and generate secondary singlet oxygen. Inactivation of further catalase molecules by secondary singlet oxygen leads to auto-amplification of singlet oxygen generation and catalase inactivation. This allows reactivation of intercellular ROS/RNS-signaling and selective apoptosis induction in tumor cells. The initial singlet oxygen generation seems to be the critical point in this complex biochemical multistep mechanism. Initial singlet oxygen generation requires the interaction between distinct tumor cell-derived ROS and RNS and may also depend on either the induction of NO synthase expression or NOX1 activation through the FAS receptor. FAS receptor activation can be achieved by singlet oxygen. Autoamplificatory generation of singlet oxygen through the interaction between peroxynitrite and hydrogen peroxide inherits a rich potential for the establishment of synergistic effects that may be instrumental for novel approaches of tumor therapy with high selectivity towards malignant cells.
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Affiliation(s)
- Georg Bauer
- Institute of Virology, Medical Center - University of Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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Yadav U, Anjaria KB, Nairy R, Shirsath KB, Desai UN, Chaurasia RK, Bhat NN, Sapra BK. Differential killing and radio-modifying effects of iodoacetate in mammalian normal and cancer cells. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2017; 56:227-239. [PMID: 28612110 DOI: 10.1007/s00411-017-0699-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 03/23/2017] [Indexed: 06/07/2023]
Abstract
To explore possible applications of iodoacetate (IA), a glycolytic inhibitor, in cancer treatment, we screened its cytotoxicity and radioprotective/sensitizing efficacy in three different mammalian cell lines; A549 (human lung carcinoma), MCF7 (human mammary cancer), a non-cancerous CHO (Chinese hamster ovary) cells and human lymphocytes. Experiments were carried out using IA concentrations ranging from 0.01 to 2.5 µg/ml, with or without 60Coγ-radiation. In the outcomes, IA was found to exhibit higher toxicity in the cancer cells, whereas it was non-toxic/marginally toxic to the non-cancerous cells. Considerably higher glucose uptake in both cancer cells lines was observed indicating higher rates of glycolysis. IA significantly inhibited glycolysis as reflected by GAPDH activity inhibition. Radiomodifying effects of IA were found to be concentration dependent in both cancerous and non-cancerous cells. The response in non-cancerous was found to be biphasic: at lower concentrations, it offered significant radioprotection; however, the protection decreased with increasing concentration. Moreover, at the highest tested concentration, marginal radiosensitization was also observed (as indicated by clonogenic assay). In both cancer cells, IA offered significant amount of radiosensitization which was considerably high at higher concentrations. Further experiments were carried out to estimate the Dose Modification Factor (DMF) to quantify and compare relative radiosensitization by IA in cancer and normal cell lines. The DMF was calculated for three different concentrations of IA, 0.5, 1, and 1.5 µg/ml, and corresponding values were found to be 1.26, 1.43, and 1.89 for A549 cancer cells, whereas for normal CHO cells, it was 1.13, 1.13, and 1.24. In conclusion, differential killing and radiosensitizing effects of IA suggest that it may have potential use as a anticancer agent and radiosensitizer in cancer therapy.
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Affiliation(s)
- Usha Yadav
- Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
| | - K B Anjaria
- Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
| | - Rajesha Nairy
- Department of Studies in Physics, Mangalore University, Mangalore, Karnataka, 574199, India
| | - K B Shirsath
- Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
| | - Utkarsha N Desai
- Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
| | - Rajesh K Chaurasia
- Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
| | - Nagesh N Bhat
- Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.
| | - B K Sapra
- Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India
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3,4 Dihydroxycinnamic acid stimulates immune system function by modifying the humoral antibody response – An in vivo study. Cell Immunol 2017; 314:10-17. [DOI: 10.1016/j.cellimm.2017.01.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 01/06/2017] [Accepted: 01/07/2017] [Indexed: 02/05/2023]
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Chen YZ, Wang ZU, Wang H, Lu J, Yu SH, Jiang HL. Singlet Oxygen-Engaged Selective Photo-Oxidation over Pt Nanocrystals/Porphyrinic MOF: The Roles of Photothermal Effect and Pt Electronic State. J Am Chem Soc 2017; 139:2035-2044. [PMID: 28103670 DOI: 10.1021/jacs.6b12074] [Citation(s) in RCA: 427] [Impact Index Per Article: 53.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The selectivity control toward aldehyde in the aromatic alcohol oxidation remains a grand challenge using molecular oxygen under mild conditions. In this work, we designed and synthesized Pt/PCN-224(M) composites by integration of Pt nanocrystals and porphyrinic metal-organic frameworks (MOFs), PCN-224(M). The composites exhibit excellent catalytic performance in the photo-oxidation of aromatic alcohols by 1 atm O2 at ambient temperature, based on a synergetic photothermal effect and singlet oxygen production. Additionally, in opposition to the function of the Schottky junction, injection of hot electrons from plasmonic Pt into PCN-224(M) would lower the electron density of the Pt surface, which thus is tailorable for the optimized catalytic performance via the competition between the Schottky junction and the plasmonic effect by altering the light intensity. To the best of our knowledge, this is not only an unprecedented report on singlet oxygen-engaged selective oxidation of aromatic alcohols to aldehydes but also the first report on photothermal effect of MOFs.
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Affiliation(s)
- Yu-Zhen Chen
- Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Suzhou Nano Science and Technology, School of Chemistry and Materials Science, University of Science and Technology of China , Hefei, Anhui 230026, People's Republic of China
| | - Zhiyong U Wang
- Department of Chemistry and Physics, Troy University , Troy, Alabama 36082, United States
| | - Hengwei Wang
- Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Suzhou Nano Science and Technology, School of Chemistry and Materials Science, University of Science and Technology of China , Hefei, Anhui 230026, People's Republic of China
| | - Junling Lu
- Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Suzhou Nano Science and Technology, School of Chemistry and Materials Science, University of Science and Technology of China , Hefei, Anhui 230026, People's Republic of China
| | - Shu-Hong Yu
- Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Suzhou Nano Science and Technology, School of Chemistry and Materials Science, University of Science and Technology of China , Hefei, Anhui 230026, People's Republic of China
| | - Hai-Long Jiang
- Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Suzhou Nano Science and Technology, School of Chemistry and Materials Science, University of Science and Technology of China , Hefei, Anhui 230026, People's Republic of China
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Microwave-assisted one pot synthesis, characterization, biological evaluation and molecular docking studies of steroidal thiazoles. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2017; 166:104-115. [DOI: 10.1016/j.jphotobiol.2016.11.010] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2016] [Accepted: 11/11/2016] [Indexed: 11/20/2022]
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Farhan M, Oves M, Chibber S, Hadi SM, Ahmad A. Mobilization of Nuclear Copper by Green Tea Polyphenol Epicatechin-3-Gallate and Subsequent Prooxidant Breakage of Cellular DNA: Implications for Cancer Chemotherapy. Int J Mol Sci 2016; 18:ijms18010034. [PMID: 28035959 PMCID: PMC5297669 DOI: 10.3390/ijms18010034] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 12/20/2016] [Accepted: 12/22/2016] [Indexed: 11/21/2022] Open
Abstract
Epidemiological as well as experimental evidence exists in support of chemopreventive and anticancer properties of green tea and its constituents. The gallocatechin, epicatechin-3-gallate is a major polyphenol present in green tea, shown responsible for these effects. Plant-derived polyphenolic compounds are established natural antioxidants which are capable of catalyzing oxidative DNA degradation of cellular DNA, alone as well as in the presence of transition metal ions, such as copper. Here we present evidence to support that, similar to various other polyphenoic compounds, epicatechin-3-gallate also causes oxidative degradation of cellular DNA. Single cell alkaline gel electrophoresis (Comet assay) was used to assess DNA breakage in lymphocytes that were exposed to various concentrations of epicatechin-3-gallate. Inhibition of DNA breakage in the presence of scavengers of reactive oxygen species (ROS) suggested involvement of ROS generation. Addition of neocuproine (a cell membrane permeable Cu(I) chelator) inhibited DNA degradation, dose-dependently, in intact lymphocytes. In contrast, bathocuproine, which does not permeate cell membrane, was observed to be ineffective. We further show that epicatechin-3-gallate degrades DNA in cell nuclei, which can also be inhibited by neocuproine, suggesting mobilization of nuclear copper in this reaction as well. Our results are indicative of ROS generation, possibly through mobilization of endogenous copper ions, and support our long-standing hypothesis of a prooxidant activity of plant-derived polyphenols as a mechanism for their documented anticancer properties.
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Affiliation(s)
- Mohd Farhan
- Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202001, India.
| | - Mohammad Oves
- Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
| | - Sandesh Chibber
- Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202001, India.
| | - Sheikh Mumtaz Hadi
- Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202001, India.
| | - Aamir Ahmad
- Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604-1405, USA.
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Cha YS, Lee KH, Lee JW, Choi EH, Kim HI, Kim OH, Cha KC, Kim H, Hwang SO. The use of delta neutrophil index and myeloperoxidase index as diagnostic predictors of strangulated mechanical bowel obstruction in the emergency department. Medicine (Baltimore) 2016; 95:e5481. [PMID: 27902604 PMCID: PMC5134774 DOI: 10.1097/md.0000000000005481] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Early detection of bowel strangulation is difficult in patients with mechanical bowel obstruction (MBO). There have been no previous reports of predicting strangulation in MBO cases using the delta neutrophil index (DNI), which is a measure of the proportion of circulating immature granulocytes, or the myeloperoxidase index (MPXI), which is a measure of serum myeloperoxidase level. Therefore, we evaluated differences in initial DNI and MPXI upon presentation at the emergency department (ED) according to strangulation presence in MBO patients.This is a retrospective observational study of consecutive patients older than 18 years who were diagnosed with MBO over a 31-month period. MBO was ultimately confirmed by computed tomography (CT) findings by a radiology specialist. Patients were categorized by a strangulation group (SG) and nonstrangulation group (NSG). The SG was defined by surgical and pathologic findings after the surgical operation. Initial serum counts of white blood cells and neutrophils, C-reactive protein levels, and DNI and MPXI scores were investigated in the ED.Fifteen of 160 patients were allocated to the SG (9.4%), and among the inflammatory markers, median initial DNI value was the only one that was significantly higher in the SG (0% vs 3.2%, P = 0.003). Although the areas under the receiver operation characteristic (ROC) curves for initial DNI and CT for differentiating strangulated from nonstrangulated bowel obstruction were 0.713 (95% confidence interval [CI]: 0.636-0.782) and 0.883 (95% CI: 0.823-0.928), respectively; there was no significant difference between DNI and CT (P = 0.147). The area under the curve (AUC) for predicting strangulated bowel disease from a combination of initial DNI score and CT findings (0.983, 95% CI: 0.948-0.997) was higher than the AUC for CT alone, although the difference was not significant (P = 0.052).In conclusion, initial DNI, which was performed in the ED, was found to be significantly higher in the SG than in the NSG. Initial DNI might be a useful additional parameter for improving the prediction accuracy of CT.
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Affiliation(s)
- Yong Sung Cha
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju
| | - Kang Hyun Lee
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju
| | - Jong Wook Lee
- Department of Laboratory Medicine, Jincheon Sungmo Hospital, Jincheon
| | - Eun Hee Choi
- Biostatistician, Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - Hyung Il Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju
| | - Oh Hyun Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju
| | - Kyoung Chul Cha
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju
| | - Hyun Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju
| | - Sung Oh Hwang
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju
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Girn HRS, Ahilathirunayagam S, Mavor AID, Homer-Vanniasinkam S. Reperfusion Syndrome: Cellular Mechanisms of Microvascular Dysfunction and Potential Therapeutic Strategies. Vasc Endovascular Surg 2016; 41:277-93. [PMID: 17704330 DOI: 10.1177/1538574407304510] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Reperfusion injury is the paradoxical and complex phenomenon of exacerbation of cellular dysfunction and increase in cell death after the restoration of blood flow to previously ischemic tissues. It involves biochemical and cellular changes causing oxidant production and complement activation, which culminates in an inflammatory response, mediated by neutrophil and platelet cell interactions with the endothelium and among the cells themselves. The mounted inflammatory response has both local and systemic manifestations. Despite improvements in imaging, interventional techniques, and pharmacological agents, morbidity from reperfusion remains high. Extensive research has furthered the understanding of the various pathophysiological mechanisms involved and the development of potential therapeutic strategies. Preconditioning has emerged as a powerful method of ameliorating ischemia reperfusion injury to the myocardium and in transplant surgery. More recently, postconditioning has been shown to provide a therapeutic counter to vasoocclusive emergencies. More research and well-designed trials are needed to bridge the gap between experimental evidence and clinical implementation.
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Kettle AJ, Winterbourn CC. Myeloperoxidase: a key regulator of neutrophil oxidant production. Redox Rep 2016; 3:3-15. [PMID: 27414766 DOI: 10.1080/13510002.1997.11747085] [Citation(s) in RCA: 484] [Impact Index Per Article: 53.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Kim OH, Cha YS, Hwang SO, Jang JY, Choi EH, Kim HI, Cha K, Kim H, Lee KH. The Use of Delta Neutrophil Index and Myeloperoxidase Index for Predicting Acute Complicated Appendicitis in Children. PLoS One 2016; 11:e0148799. [PMID: 26859663 PMCID: PMC4747520 DOI: 10.1371/journal.pone.0148799] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 01/22/2016] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND In children with acute appendicitis, 30% to 75% present with a complication, such as perforation, and the early diagnosis of complications is known to improve outcomes. Serum delta neutrophil index (DNI) and myeloperoxidase index (MPXI) are new inflammatory markers, and thus, in the present study, the authors evaluated the predictive values of these two markers for the presence of a complication in children with acute appendicitis. METHODS This retrospective observational study was conducted on 105 consecutive children (<12 years old) with acute appendicitis treated over a 31-month period. DNI, MPXI, C-reactive protein (CRP), and white blood cells (WBCs) were measured in an emergency department and investigated with respect to their abilities to predict the presence of acute complicated appendicitis. RESULTS Twenty-nine of the 105 patients (median age, 9 years) were allocated to the complicated group (27.6%) and 76 to the non-complicated group (72.4%). Median serum DNI and CRP were significantly higher in the complicated group [0% vs. 2.2%, p<0.001 and 0.65 mg/dL vs. 8.0 mg/dL, p<0.001], but median MPXI was not (p = 0.316). Area under curve (AUC) for the ability of serum DNI and CRP to predict the presence of acute complicated appendicitis were 0.738 and 0.840, respectively. Multiple logistic regression analyses showed initial CRP [odds ratio 1.301, 95% confidence interval (1.092-1.549), p = 0.003] significantly predicted the presence of a complication. The optimal cutoff for serum CRP was 4.0 mg/dL (sensitivity 69%, specificity 83%, AUC 0.840). CONCLUSIONS Although serum DNI values were significantly higher in children with acute complicated appendicitis, no evidence was obtained to support the notion that serum DNI or serum MPXI aid the differentiation of acute complicated and non-complicated appendicitis in the ED setting.
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Affiliation(s)
- Oh Hyun Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - Yong Sung Cha
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
- * E-mail:
| | - Sung Oh Hwang
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - Ji Young Jang
- Department of Surgery, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - Eun Hee Choi
- Biostatistician, Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - Hyung Il Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - KyoungChul Cha
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - Hyun Kim
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
| | - Kang Hyun Lee
- Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea
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McGrath JJ. Accelerated pre-weaning growth rates in dairy calves: do antioxidants have a place? ANIMAL PRODUCTION SCIENCE 2016. [DOI: 10.1071/an15310] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Accelerated growth of dairy calves in the pre-weaning phase has been shown to increase productivity of dairy cows during their lifetime. The increased weight gain during the pre-weaning phase is not the driving factor behind the changes in life-time productivity as the weight gained is inconsequential in terms of pre-lactation and weight gain. Furthermore, there are no differences in weight of heifers at the start of first lactation. The increased weight gain during the pre-weaning period must, therefore, initiate cellular changes within the animal. Research has focussed on increasing total nutritional supply or an increase in protein supply for promotion of such changes. The benefits of antioxidants in animal nutrition have been known for a long period of time. However, they have gained prominence with enforced reduction in use of antibiotics in many animal production systems. The role of antioxidants in nutrition of both the calf and the dam before parturition is critical for preventing disease and optimising growth weight of the pre-weaned calf. However, studies are yet to demonstrate a role, outside of preventive health, for the use of antioxidants in the pre-weaning period for increasing total life-time production of the dairy cow.
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Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study. Int J Mol Sci 2015; 16:26754-69. [PMID: 26569217 PMCID: PMC4661851 DOI: 10.3390/ijms161125992] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 10/29/2015] [Accepted: 10/30/2015] [Indexed: 11/16/2022] Open
Abstract
Epidemiological studies have linked dietary consumption of plant polyphenols with lower incidence of various cancers. In particular, flavonoids (present in onion, tomato and other plant sources) induce apoptosis and cytotoxicity in cancer cells. These can therefore be used as lead compounds for the synthesis of novel anticancer drugs with greater bioavailability. In the present study, we examined the chemical basis of cytotoxicity of flavonoids by studying the structure–activity relationship of myricetin (MN), fisetin (FN), quercetin (QN), kaempferol (KL) and galangin (GN). Using single cell alkaline gel electrophoresis (comet assay), we established the relative efficiency of cellular DNA breakage as MN > FN > QN > KL > GN. Also, we determined that the cellular DNA breakage was the result of mobilization of chromatin-bound copper ions and the generation of reactive oxygen species. The relative DNA binding affinity order was further confirmed using molecular docking and thermodynamic studies through the interaction of flavonoids with calf thymus DNA. Our results suggest that novel anti-cancer molecules should have ortho-dihydroxy groups in B-ring and hydroxyl groups at positions 3 and 5 in the A-ring system. Additional hydroxyl groups at other positions further enhance the cellular cytotoxicity of the flavonoids.
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Malkin AD, Sheehan RP, Mathew S, Federspiel WJ, Redl H, Clermont G. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis. PLoS Comput Biol 2015; 11:e1004314. [PMID: 26468651 PMCID: PMC4607502 DOI: 10.1371/journal.pcbi.1004314] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 05/01/2015] [Indexed: 11/18/2022] Open
Abstract
Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8), a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3–6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40–80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5–24 hours, which may reduce survival to 13%. In severe sepsis, an extracorporeal treatment which modulates CXCR-1/2 levels has therapeutic potential, but also potential for harm. Further development of the computational model will help guide optimal device development and determine which patient populations should be targeted by treatment. Sepsis occurs when a patient develops a whole body immune response due to infection. In this condition, white blood cells called neutrophils circulate in an active state, seeking and eliminating invading bacteria. However, when neutrophils are activated, healthy tissue is inadvertently targeted, leading to organ damage and potentially death. Even though sepsis kills millions worldwide, there are still no specific treatments approved in the United States. This may be due to the complexity and diversity of the body’s immune response, which can be managed well using computational modeling. We have developed a computational model to predict how different levels of neutrophil activation impact survival in an overactive inflammatory conditions. The model was utilized to assess the effectiveness of a simulated experimental sepsis treatment which modulates neutrophil populations and activity. This evaluation determined that treatment timing plays a critical role in therapeutic effectiveness. When utilized properly the treatment drastically improves survival, but there is also risk of causing patient harm when introduced at the wrong time. We intend for this computational model to support and guide further development of sepsis treatments and help translate these preliminary results from bench to bedside.
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Affiliation(s)
- Alexander D. Malkin
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- * E-mail:
| | - Robert P. Sheehan
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Shibin Mathew
- Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - William J. Federspiel
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Heinz Redl
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in AUVA center, Vienna, Austria
| | - Gilles Clermont
- CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
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Coady A, Xu M, Phung Q, Cheung TK, Bakalarski C, Alexander MK, Lehar SM, Kim J, Park S, Tan MW, Nishiyama M. The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst. PLoS One 2015; 10:e0138350. [PMID: 26379037 PMCID: PMC4574778 DOI: 10.1371/journal.pone.0138350] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 07/31/2015] [Indexed: 01/04/2023] Open
Abstract
Manganese plays a central role in cellular detoxification of reactive oxygen species (ROS). Therefore, manganese acquisition is considered to be important for bacterial pathogenesis by counteracting the oxidative burst of phagocytic cells during host infection. However, detailed analysis of the interplay between bacterial manganese acquisition and phagocytic cells and its impact on bacterial pathogenesis has remained elusive for Staphylococcus aureus, a major human pathogen. Here, we show that a mntC mutant, which lacks the functional manganese transporter MntABC, was more sensitive to killing by human neutrophils but not murine macrophages, unless the mntC mutant was pre-exposed to oxidative stress. Notably, the mntC mutant formed strikingly small colonies when recovered from both type of phagocytic cells. We show that this phenotype is a direct consequence of the inability of the mntC mutant to reinitiate growth after exposure to phagocytic oxidative burst. Transcript and quantitative proteomics analyses revealed that the manganese-dependent ribonucleotide reductase complex NrdEF, which is essential for DNA synthesis and repair, was highly induced in the mntC mutant under oxidative stress conditions including after phagocytosis. Since NrdEF proteins are essential for S. aureus viability we hypothesize that cells lacking MntABC might attempt to compensate for the impaired function of NrdEF by increasing their expression. Our data suggest that besides ROS detoxification, functional manganese acquisition is likely crucial for S. aureus pathogenesis by repairing oxidative damages, thereby ensuring efficient bacterial growth after phagocytic oxidative burst, which is an attribute critical for disseminating and establishing infection in the host.
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Affiliation(s)
- Alison Coady
- Department of Infectious Diseases, Genentech Inc., South San Francisco, California, United States of America
| | - Min Xu
- Department of Translational Immunology, Genentech Inc., South San Francisco, California, United States of America
| | - Qui Phung
- Department of Protein Chemistry, Genentech Inc., South San Francisco, California, United States of America
| | - Tommy K. Cheung
- Department of Protein Chemistry, Genentech Inc., South San Francisco, California, United States of America
| | - Corey Bakalarski
- Department of Protein Chemistry, Genentech Inc., South San Francisco, California, United States of America
- Department of Bioinformatics, Genentech Inc., South San Francisco, California, United States of America
| | - Mary Kate Alexander
- Department of Infectious Diseases, Genentech Inc., South San Francisco, California, United States of America
| | - Sophie M. Lehar
- Department of Infectious Diseases, Genentech Inc., South San Francisco, California, United States of America
| | - Janice Kim
- Department of Translational Immunology, Genentech Inc., South San Francisco, California, United States of America
| | - Summer Park
- Department of Translational Immunology, Genentech Inc., South San Francisco, California, United States of America
| | - Man-Wah Tan
- Department of Infectious Diseases, Genentech Inc., South San Francisco, California, United States of America
| | - Mireille Nishiyama
- Department of Infectious Diseases, Genentech Inc., South San Francisco, California, United States of America
- * E-mail:
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Bauer G. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells. Redox Biol 2015; 6:353-371. [PMID: 26342455 PMCID: PMC4564397 DOI: 10.1016/j.redox.2015.07.017] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Revised: 07/21/2015] [Accepted: 07/29/2015] [Indexed: 12/21/2022] Open
Abstract
Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of NO metabolism and direct catalase inhibitors. The latter aspect is explicitely studied for the interaction between catalase inhibiting acetylsalicylic acid and an NO donor. It is also shown that hybrid molecules like NO-aspirin utilize this synergistic potential. Our data open novel approaches for rational tumor therapy based on specific ROS signaling and its control in tumor cells.
Membrane-associated catalase protects tumor cells against ROS/RNS signaling. NO can be oxidated by catalase, but can also reversibly inhibit the enzyme. ONOO− is decomposed by catalase but also drives its inactivation through singlet oxygen. Modulation of the NO level triggers singlet oxygen generation and catalase inactivation. This signaling network allows to establish synergistic antitumor effects.
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Affiliation(s)
- Georg Bauer
- Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center Freiburg, Hermann-Herder Strasse 11, D-79104 Freiburg, Germany.
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Riethmüller M, Burger N, Bauer G. Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling. Redox Biol 2015. [PMID: 26225731 PMCID: PMC4532730 DOI: 10.1016/j.redox.2015.07.006] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2(.)) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling.
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Affiliation(s)
- Michaela Riethmüller
- Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg, Germany
| | - Nils Burger
- Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg, Germany
| | - Georg Bauer
- Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg, Germany.
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50
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Sheng H, Nakamura K, Kanno T, Sasaki K, Niwano Y. Bactericidal Effect of Photolysis of H2O2 in Combination with Sonolysis of Water via Hydroxyl Radical Generation. PLoS One 2015; 10:e0132445. [PMID: 26148024 PMCID: PMC4493093 DOI: 10.1371/journal.pone.0132445] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 06/15/2015] [Indexed: 11/21/2022] Open
Abstract
The bactericidal effect of hydroxyl radical (·OH) generated by combination of photolysis of hydrogen peroxide (H2O2) and sonolysis of water was examined under the condition in which the yield of ·OH increased additively when H2O2 aqueous solution was concomitantly irradiated with laser and ultrasound. The suspension of Staphylococcus aureus mixed with the different concentrations of H2O2 was irradiated simultaneously with a laser light (wavelength: 405 nm, irradiance: 46 and 91 mW/cm2) and ultrasound (power: 30 w, frequency: 1.65 MHz) at 20 ± 1°C of the water bulk temperature for 2 min. The combination of laser and ultrasound irradiation significantly reduced the viable bacterial count in comparison with the laser irradiation of H2O2 alone. By contrast, the ultrasound irradiation alone exerted almost no bactericidal effect. These results suggested that the combination effect of photolysis of H2O2 and sonolysis of water on bactericidal activity was synergistic. A multi-way analysis of variance also revealed that the interaction of H2O2 concentration, laser power and ultrasound irradiation significantly affected the bactericidal activity. Since the result of oxidative DNA damage evaluation demonstrated that the combination of laser and ultrasound irradiation significantly induced oxidative damage of bacterial DNA in comparison with the laser irradiation of H2O2 alone, it was suggested that the combination effect of photolysis of H2O2 and sonolysis of water on bactericidal activity would be exerted via oxidative damage of cellular components such as DNA.
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Affiliation(s)
- Hong Sheng
- Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
- * E-mail:
| | - Keisuke Nakamura
- Laboratory for Redox Regulation, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
| | - Taro Kanno
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
| | - Keiichi Sasaki
- Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
| | - Yoshimi Niwano
- Laboratory for Redox Regulation, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
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