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1.
Data Processing to Probe the Cellular Hydrogen Peroxide Landscape.
Antunes, F, Brito, P
Methods in molecular biology (Clifton, N.J.). 2022;:153-160
Abstract
Hydrogen peroxide (H2O2) regulates signaling pathways by modulating the activity of redox-sensitive proteins denominated redox switches. The magnitude of the transient variations in localized H2O2 pools during signaling events and how these variations impact redox switches present in the cell remain elusive. A canonical model with two chemical reactions comprising the oxidation/reduction cycle of a redox switch is described. The model is dimensionless with respect to the redox switch concentration. Thus, the time-series data required to apply the equations deduced is the percentage of oxidation of a redox switch, avoiding the application of absolute concentrations that are often difficult to measure experimentally. Here, we describe detailed protocols for the processing of experimental data with the canonical model to probe the absolute concentrations of H2O2 found in the vicinity of redox switches and probes, as well as the kinetic parameters that describe the reduction and oxidation of redox switches. The protocols are an analytical tool that helps to depict the cellular hydrogen peroxide signaling landscape, giving new insights on H2O2 signaling mechanisms, and hold the potential to be a framework for a future redox kinetomics analytical platform.
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2.
Hydrogen peroxide-induced stress acclimation in plants.
Qureshi, MK, Gawroński, P, Munir, S, Jindal, S, Kerchev, P
Cellular and molecular life sciences : CMLS. 2022;(2):129
Abstract
Among all reactive oxygen species (ROS), hydrogen peroxide (H2O2) takes a central role in regulating plant development and responses to the environment. The diverse role of H2O2 is achieved through its compartmentalized synthesis, temporal control exerted by the antioxidant machinery, and ability to oxidize specific residues of target proteins. Here, we examine the role of H2O2 in stress acclimation beyond the well-studied transcriptional reprogramming, modulation of plant hormonal networks and long-distance signalling waves by highlighting its global impact on the transcriptional regulation and translational machinery.
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3.
Recent Advances in Hydrogen Peroxide Responsive Organoborons for Biological and Biomedical Applications.
Saxon, E, Peng, X
Chembiochem : a European journal of chemical biology. 2022;(3):e202100366
Abstract
Hydrogen peroxide is the most stable reactive oxygen species generated endogenously, participating in numerous physiological processes and abnormal pathological conditions. Mounting evidence suggests that a higher level of H2 O2 exists in various disease conditions. Thus, H2 O2 functions as an ideal target for site-specific bioimaging and therapeutic targeting. The unique reactivity of organoborons with H2 O2 provides a method for developing chemoselective molecules for biological and biomedical applications. This review highlights the design and application of boron-derived molecules for H2 O2 detection, and the utility of boron moieties toward masking reactive compounds leading to the development of metal prochelators and prodrugs for selectively delivering an active species at the target sites with elevated H2 O2 levels. Additionally, the emergence of H2 O2 -responsive theranostic agents consisting of both therapeutic and diagnostic moieties in one integrated system are discussed. The purpose of this review is to provide a better understanding of the role of boron-derived molecules toward biological and pharmacological applications.
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4.
Dual Role of Hydrogen Peroxide as an Oxidant in Pneumococcal Pneumonia.
Mraheil, MA, Toque, HA, La Pietra, L, Hamacher, J, Phanthok, T, Verin, A, Gonzales, J, Su, Y, Fulton, D, Eaton, DC, et al
Antioxidants & redox signaling. 2021;(12):962-978
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Abstract
Significance:Streptococcus pneumoniae (Spn), a facultative anaerobic Gram-positive human pathogen with increasing rates of penicillin and macrolide resistance, is a major cause of lower respiratory tract infections worldwide. Pneumococci are a primary agent of severe pneumonia in children younger than 5 years and of community-acquired pneumonia in adults. A major defense mechanism toward Spn is the generation of reactive oxygen species, including hydrogen peroxide (H2O2), during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn produces high endogenous levels of H2O2 as a strategy to promote colonization. Recent Advances: Pneumococci, which express neither catalase nor common regulators of peroxide stress resistance, have developed unique mechanisms to protect themselves from H2O2. Spn generates high levels of H2O2 as a strategy to promote colonization. Production of H2O2 moreover constitutes an important virulence phenotype and its cellular activities overlap and complement those of other virulence factors, such as pneumolysin, in modulating host immune responses and promoting organ injury. Critical Issues: This review examines the dual role of H2O2 in pneumococcal pneumonia, from the viewpoint of both the pathogen (defense mechanisms, lytic activity toward competing pathogens, and virulence) and the resulting host-response (inflammasome activation, endoplasmic reticulum stress, and damage to the alveolar-capillary barrier in the lungs). Future Directions: An understanding of the complexity of H2O2-mediated host-pathogen interactions is necessary to develop novel strategies that target these processes to enhance lung function during severe pneumonia.
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Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic-Synergized Multimodal Therapy.
Zhou, Y, Fan, S, Feng, L, Huang, X, Chen, X
Advanced materials (Deerfield Beach, Fla.). 2021;(48):e2104223
Abstract
Chemodynamic therapy (CDT) uses the tumor microenvironment-assisted intratumoral Fenton reaction for generating highly toxic hydroxyl free radicals (•OH) to achieve selective tumor treatment. However, the limited intratumoral Fenton reaction efficiency restricts the therapeutic efficacy of CDT. Recent years have witnessed the impressive development of various strategies to increase the efficiency of intratumoral Fenton reaction. The introduction of these reinforcement strategies can dramatically improve the treatment efficiency of CDT and further promote the development of enhanced CDT (ECDT)-based multimodal anticancer treatments. In this review, the authors systematically introduce these reinforcement strategies, from their basic working principles, reinforcement mechanisms to their representative clinical applications. Then, ECDT-based multimodal anticancer therapy is discussed, including how to integrate these emerging Fenton reinforcement strategies for accelerating the development of multimodal anticancer therapy, as well as the synergistic mechanisms of ECDT and other treatment methods. Eventually, future direction and challenges of ECDT and ECDT-based multimodal synergistic therapies are elaborated, highlighting the key scientific problems and unsolved technical bottlenecks to facilitate clinical translation.
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Hydrogen Peroxide Does Not Significantly Reduce Cutibacterium acnes Suture Contamination in Arthroscopic Rotator Cuff Repair.
Yamakado, K
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2021;(4):1134-1140
Abstract
PURPOSE To evaluate the efficacy of application of the 3% hydrogen peroxide (HP)-soaked gauze as an addition to the standard preoperative sterile skin preparation for Cutibacterium acnes suture contamination in arthroscopic rotator cuff repairs. METHODS A prospective randomized study was undertaken to evaluate 151 consecutive patients undergoing arthroscopic rotator cuff repair. Each shoulder was prepared with 1 of the 2 randomly selected protocols: chlorhexidine alcohol (1% chlorhexidine gluconate in 70% isopropyl alcohol)(control group) and chlorhexidine alcohol with 3% HP (HP-treated group). In the HP-treated group, the 3% HP-soaked gauze was applied over the shoulder for 5 minutes before the application of the chlorhexidine-alcohol. The first cut-tails of the anchor suture after cuff fixation were submitted to aerobic and anaerobic cultures. Patients were clinically evaluated for infection 10 days, 28 days, 3 months, 6 months, and 12 months after surgery. RESULTS The rate of C acnes-positive cultures was 13.0% (10 of 77 cases) in the control group and 6.8% (5 of 74 cases) in the HP-treated group. The HP-treated group showed a trend of lower C acnes-positive culture rate, which did not reach statistical significance (relative risk, 0.52; 95% confidence interval, 0.19 and 1.45; number needed to treat, 16.1; P = .20). One case of coagulase-negative Staphylococcus (Staphylococcus intermedius) was isolated in the HP-treated group (1 of 74 cases, 1.3%). No other bacteria were isolated. No infections occurred in any of the patients treated in this study during the minimum 3-month follow-up period. One patient in the HP-treated group complained of skin irritation. CONCLUSIONS The use of a 3% HP-soaked gauze as an addition to the standard preoperative sterile skin preparation for arthroscopic rotator cuff repairs showed only a marginal effect (statistically insignificant) in reducing the C acnes suture contamination rate in the arthroscopic rotator cuff repair patients. LEVEL OF EVIDENCE I, prospective, randomized trial.
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Systems Biology Approaches to Enzyme Kinetics.
Finn, NA, Raddatz, AD, Kemp, ML
Methods in molecular biology (Clifton, N.J.). 2021;:419-440
Abstract
Intracellular drug metabolism involves transport, bioactivation, conjugation, and other biochemical steps. The dynamics of these steps are each dependent on a number of other cellular factors that can ultimately lead to unexpected behavior. In this review, we discuss the confounding processes and coupled reactions within bioactivation networks that require a systems-level perspective in order to fully understand the time-varying behavior. When converting known in vitro characteristics of drug-enzyme interactions into descriptions of cellular systems, features such as substrate availability, cell-to-cell variability, and intracellular redox state, deserve special focus. Two examples are provided. First, a model of hydrogen peroxide clearance during chemotherapy treatment serves as a basis to discuss an example of sensitivity analysis. Second, an example of doxorubicin bioactivation is used for discussing points of consideration when constructing and analyzing network models of drug metabolism.
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Heterogeneous Fenton catalysts: A review of recent advances.
Thomas, N, Dionysiou, DD, Pillai, SC
Journal of hazardous materials. 2021;(Pt B):124082
Abstract
Heterogeneous Fenton catalysts are emerging as excellent materials for applications related to water purification. In this review, recent trends in the synthesis and application of heterogeneous Fenton catalysts for the abatement of organic pollutants and disinfection of microorganisms are discussed. It is noted that as the complexity of cell wall increases, the resistance level towards various disinfectants increases and it requires either harsh conditions or longer exposure time for the complete disinfection. In case of viruses, enveloped viruses (e.g. SARS-CoV-2) are found to be more susceptible to disinfectants than the non-enveloped viruses. The introduction of plasmonic materials with the Fenton catalysts broadens the visible light absorption efficiency of the hybrid material, and incorporation of semiconductor material improves the rate of regeneration of Fe(II) from Fe(III). A special emphasis is given to the use of Fenton catalysts for antibacterial applications. Composite materials of magnetite and ferrites remain a champion in this area because of their easy separation and reuse, owing to their magnetic properties. Iron minerals supported on clay materials, perovskites, carbon materials, zeolites and metal-organic frameworks (MOFs) dramatically increase the catalytic degradation rate of contaminants by providing high surface area, good mechanical stability, and improved electron transfer. Moreover, insights to the zero-valent iron and its capacity to remove a wide range of organic pollutants, heavy metals and bacterial contamination are also discussed. Real world applications and the role of natural organic matter are summarised. Parameter optimisation (e.g. light source, dosage of catalyst, concentration of H2O2 etc.), sustainable models for the reusability or recyclability of the catalyst and the theoretical understanding and mechanistic aspects of the photo-Fenton process are also explained. Additionally, this review summarises the opportunities and future directions of research in the heterogeneous Fenton catalysis.
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Structural characterization of a polysaccharide from Radix Hedysari and its protective effects against H2O2-induced injury in human gastric epithelium cells.
Xue, Z, Zhao, L, Wang, D, Chen, X, Liu, D, Liu, X, Feng, S
International journal of biological macromolecules. 2021;:503-515
Abstract
The gastroprotective effects of polysaccharides had become a hot topic in the field of functional polysaccharides research. Three polysaccharides, namely HPS-80-1, HPS-80-2, and HPS-80-3 were purified by DEAE-52 column chromatography. The thermodynamic characteristics, scanning electron microscopy, and Congo red experimental results of the above polysaccharides were greatly distinctive. Then a mature GES-1 oxidative stress cell model induced by H2O2 was established to screen out subsequent research subjects. It turned out that HPS-80-1 had a desirable protective effect, which was confirmed by analyses of cell cycle & apoptosis, and oxidative stress-related factors in the cell culture media, and so on. Furthermore, Structural features demonstrated that the backbone of HPS-80-1 appeared to mainly consist of →4)-α-D-Glcp-(1→, →4,6)-β-L-Glcp-(1→, and →6)-α-D-Galp-(1→, with branches at O-1, O-4, and O-6 position consisting of →2,4)-β-D-Rhap-(1→, →1)-α-D-Galp-(4→, and →3,4)-α-D-Manp-(1→. It was speculated that the excellent gastric mucosal protective activity of HPS-80-1 may be due to the high amount of glucose in the backbone. In addition, it was also related to the anti-inflammatory activity and antioxidant bases such as (1 → 4)-Glcp and (1 → 6)-Galp in the structure of HPS-80-1. These findings provide a scientific basis for further utilization of polysaccharides from Radix Hedysari.
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10.
Interplay between hydrogen sulfide and other signaling molecules in the regulation of guard cell signaling and abiotic/biotic stress response.
Liu, H, Xue, S
Plant communications. 2021;(3):100179
Abstract
Stomatal aperture controls the balance between transpirational water loss and photosynthetic carbon dioxide (CO2) uptake. Stomata are surrounded by pairs of guard cells that sense and transduce environmental or stress signals to induce diverse endogenous responses for adaptation to environmental changes. In a recent decade, hydrogen sulfide (H2S) has been recognized as a signaling molecule that regulates stomatal movement. In this review, we summarize recent progress in research on the regulatory role of H2S in stomatal movement, including the dynamic regulation of phytohormones, ion homeostasis, and cell structural components. We focus especially on the cross talk among H2S, nitric oxide (NO), and hydrogen peroxide (H2O2) in guard cells, as well as on H2S-mediated post-translational protein modification (cysteine thiol persulfidation). Finally, we summarize the mechanisms by which H2S interacts with other signaling molecules in plants under abiotic or biotic stress. Based on evidence and clues from existing research, we propose some issues that need to be addressed in the future.