Removal Of H2O2 Research Articles

Affinity of class I and class III peroxidases for H2O2 in pepper leaves of different maturity

Paper deals with activities of Class III peroxidases (POX, EC 1.11.1.7) and Class I peroxidases (ascorbate peroxidase, APX, EC 1.11.1.11) as well as the Km of these enzymes for hydrogen peroxide (H2O2) in the pepper leaves of different maturity. The obtained results suggest that the youngest pepper leaves compared to more mature ones have different strategies for H2O2 removal. There was an increase in APX activity with leaf maturity, while POX activity had the opposite trend, and its lowest activity was observed in the oldest leaves. The accumulation of reducing substrates i.e., ascorbate and total phenols was in positive correlation with corresponding enzymes following leaf maturity. The comparison of POX and APX affinity for H2O2 in pepper leaves of different maturity and their relationship between these enzymes' activities were showed.

Substance-P Restores Cellular Activity of ADSC Impaired by Oxidative Stress.

Oxidative stress induces cellular damage, which accelerates aging and promotes the development of serious illnesses. Adipose-derived stem cells (ADSCs) are novel cellular therapeutic tools and have been applied for tissue regeneration. However, ADSCs from aged and diseased individuals may be affected in vivo by the accumulation of free radicals, which can impair their therapeutic efficacy. Substance-P (SP) is a neuropeptide that is known to rescue stem cells from senescence and inflammatory attack, and this study explored the restorative effect of SP on ADSCs under oxidative stress. ADSCs were transiently exposed to H2O2, and then treated with SP. H2O2 treatment decreased ADSC cell viability, proliferation, and cytokine production and this activity was not recovered even after the removal of H2O2. However, the addition of SP increased cell viability and restored paracrine potential, leading to the accelerated repopulation of ADSCs injured by H2O2. Furthermore, SP was capable of activating Akt/GSK-3β signaling, which was found to be downregulated following H2O2 treatment. This might contribute to the restorative effect of SP on injured ADSCs. Collectively, SP can protect ADSCs from oxidant-induced cell damage, possibly by activating Akt/GSK-3β signaling in ADSCs. This study supports the possibility that SP can recover cell activity from oxidative stress-induced dysfunction.

Determination of the antioxidant, antimicrobial and anticancer properties of the honey phenolic extract of five different regions of Bingöl province

Bingol is a famous region for honey in Turkey. The amount of phenolic substance is also considered important for the anticancer, antioxidant and antimicrobial properties of honey. Anticancer activity of honey extract was determined as the most effective dose of 1mg/mL using the WST1 anti-proliferation kit in the PC-3 cell line. Total phenol content were found between 476.09 ± 1.67 and 865.22 ± 3.57mg GAE/100g honey, total flavonoid content 41.67 ± 0.25 and 1249.74 ± 0.85mg QE/100g honey, total phenolic acid content 0.74 ± 0.21 and 58.35 ± 1.56mg SA/100g honey, β-carotene 1.71 ± 0.06-3.61 ± 0.08mg/kg honey, lycopene content 0.89 ± 0.03 and 3.41 ± 0.08mg/kg honey, respectively. Percent removal of H2O2 was determined in the range of 69.79 ± 1.24 and 75.37 ± 1.72 at 10mg/mL. DPPH percentage removal for 200mg/mL was between 69.79 ± 1.24 and 75.37 ± 1.72. Phenolic compounds in honey extract were determined as gallic acid, caffeic acid, syringe acid, chlorogenic acid, p-coumaric acid, ferulic acid, catechin, quercetin, chrysin using HPLC analysis. The honey extracts were tested on Gram(+) and Gram(-) bacteria and yeast and their antimicrobial effects were determined. As a result, phenolic honey extraction, performed from five loci from the region of interest, showed anticancer, antioxidant and antimicrobial properties, and can be used as a functional food additive to replace synthetic counterparts.

Bile acid-based dual-functional prodrug nanoparticles for bone regeneration through hydrogen peroxide scavenging and osteogenic differentiation of mesenchymal stem cells

A high level of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) upregulates pro-inflammatory cytokines and inhibits the osteogenic differentiation of mesenchymal stem cells (MSCs), which are key factors in bone regeneration. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has antioxidant and anti-inflammatory activities and also plays beneficial roles in bone regeneration by stimulating the osteogenic differentiation of MSCs while suppressing their adipogenic differentiation. Despite its remarkable capacity for bone regeneration, multiple injections of UDCA induce adverse side effects such as mechanical stress and contamination in bone defects. To fully exploit the beneficial roles of UDCA, a concept polymeric prodrug was developed based on the hypothesis that removal of overproduced H2O2 will potentiate the osteogenic functions of UDCA. In this work, we report bone regenerative nanoparticles (NPs) formulated from a polymeric prodrug of UDCA (PUDCA) with UDCA incorporated in its backbone through H2O2-responsive peroxalate linkages. The PUDCA NPs displayed potent antioxidant and anti-inflammatory activities in MSCs and induced osteogenic rather than adipogenic differentiation of the MSCs. In rat models of bone defect, the PUDCA NPs exhibited significantly better bone regeneration capacity and anti-inflammatory effects than equivalent amounts of UDCA. We anticipate that PUDCA NPs have tremendous translational potential as bone regenerative agents.

Quercetin treatment increases H2O2 removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy.

Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. The flavonoid quercetin is a potent ROS scavenger, with several beneficial effects for the cardiovascular system, including antihypertrophic effects. Oxidative imbalance has been implicated in cardiac hypertrophy and heart failure. In this work, we tested whether quercetin could attenuate cardiac hypertrophy by improving redox balance and mitochondrial homeostasis. To test this hypothesis, we treated a group of mice with isoproterenol (30mg/kg/day) for 4 or 8 consecutive days. Another group received quercetin (10mg/kg/day) from day 5th of isoproterenol treatment. We carried out the following assays in cardiac tissue: measurement of cardiac hypertrophy, protein sulfhydryl, catalase, Cu/Zn and Mn-superoxide dismutase (SOD) activity, detection of H2O2, and opening of the mitochondrial permeability transition pore. The animals treated with isoproterenol for the initial 4days showed increased cardiac weight/tibia length ratio, decreased protein sulfhydryl content, compromised SOD and catalase activity, and high H2O2 levels. Quercetin was able to attenuate cardiac hypertrophy, restore protein sulfhydryl, and antioxidant activity, in addition to efficiently blocking the H2O2. We also observed that isoproterenol decreases mitochondrial SOD activity, while quercetin reverses it. Strikingly, quercetin also protects mitochondria against the opening of mitochondrial permeability transition pore. Taken together, these results suggest that quercetin is capable of reversing established isoproterenol-induced cardiac hypertrophy through the restoration of cellular redox balance and protecting mitochondria.

Effect of removal of organic material on stable isotope ratios in skeletal carbonate from taxonomic groups with complex mineralogies.

Stable oxygen and carbon isotope ratios are one of the most accurate ways of determining environmental changes in the past, which are used to predict future environmental change. Biogenic carbonates from marine organisms are the most common source of samples for stable isotope analysis. Before they are analyzed by mass spectrometry, any organic material is traditionally removed by one of three common pretreatment methods: roasting, bleaching, or with hydrogen peroxide at various strengths and durations. This study compares δ18 O and δ13 C values in a control with no pretreatment with those from five different pretreatment methods using conventional acid digestion mass spectrometry. The objectives are to: assess the impact of the most common pretreatment methods on δ18 O and δ13 C values from (1) taxonomically underrepresented groups in previous studies, and (2) those that precipitate a wide range of biomineralogies, in the debate of whether to pretreat or not to pretreat. We analyzed the following biomineralogically complex temperate marine organisms from southern New Zealand: four species of bryozoans, four species of molluscs, two species of arthropods, and one species each of annelid, red alga, brachiopod, and echinoderm (test plates and spines treated separately). These species precipitate aragonite, High-, Intermediate-, and/or Low-Mg calcite (LMC) in their skeletons. We used linear mixed statistical models to compare the effects of the pretreatments and mineralogical composition on their δ18 O and δ13 C values. Roasting was the most effective pretreatment for the removal of organic matter and light H2 O2 the least, but the former had corresponding impacts on isotope ratios. δ18 O values were not directly affected by wt% MgCO3 , but they were significantly affected by the interaction of roasting and wt% MgCO3 . This same negative effect of roasting on species with higher wt% MgCO3 occurred in δ13 C values, but it was much more pronounced in δ18 O values. Both H2 O2 pretreatments significantly and negatively affected δ18 O values at higher wt% MgCO3 . Neither bleaching pretreatment significantly affected δ18 O values. δ13 C values were most negatively affected in skeletons with high wt% MgCO3 . There was also a strong negative roasting effect and more so at higher wt% MgCO3 . Bleaching and H2 O2 did not significantly affect δ13 C values. Based on these results, and when using skeletal carbonate of complex mineralogies, we recommend considering the abandonment of pretreatment of biogenic carbonate for stable isotope analysis due to confounded results from previous studies, difficulties with preparation, and/or the absence of significant effects of organic material on isotope ratios. If pretreatment is necessary, avoid roasting especially at higher temperatures and durations, use minimal bleaching, and in general avoid using High-Mg calcite species in O and C stable isotope studies. If bleaching is used, clearly indicate the concentration and duration of exposure.

Reactive Green 5-Decorated Polyacrylamide/Chitosan Cryogel: An Affinity Matrix for Catalase.

Acrylamide/chitosan-based cryogel was fabricated, and a triazine dye, Reactive Green 5, was attached to the cryogel by nucleophilic substitution to build a dye affinity support for adsorption of catalase enzyme. Characterization of cryogel was performed using FTIR, SEM, EDX, BET, and swelling test. Synthesized cryogel beared pores with ~ 200μm in size and the surface area of 11.8m2/g. Maximum catalase adsorption was (17.6 ± 0.29mg/g) measured at pH4.0 and 25°C. The adsorption sites on the cryogel were saturated at 0.75mg/mL enzyme concentration. Increased ionic strength caused a decrease in adsorption capacity. Desorption of catalase from cryogel was enabled using 0.5M NaSCN solution. Consecutive adsorption experiments were carried out fifteen times to evaluate the reusability of the cryogel. Thermal, storage, and operational stabilities of immobilized catalase were higher than the free one. The data produced implicate that catalase-adsorbed dye-affinity cryogel may be used for H2O2 detection or removal when necessary. Graphical Abstract.

Enzymatic preparation of pyruvate by a whole-cell biocatalyst coexpressing l-lactate oxidase and catalase

Enzymatic oxidative dehydrogenation of biomass-derived l-lactate in the presence of O2 is regarded as a green alternative for pyruvate production, but the process also results in H2O2 accumulation. To remove the effect of H2O2 on pyruvate production, various potential catalases from different species were screened for their efficiency in H2O2 degradation. Then, an in vitro cascade biocatalysis was designed using lactate oxidase from Aerococcus viridans (AvLOX) and catalase from Ureibacillus thermosphaericus (UtCAT). The in situ removal of H2O2 by UtCAT significantly improved the yield and productivity of pyruvate. To simplify the technological processes and reduce production costs, a whole cell biocatalyst without the addition of catalase for the production of pyruvate was established by coexpressing AvLOX and UtCAT in Escherichia coli. By applying suitable coexpression strategies and changing the ribosome binding site (RBS) strengths, the optimal ratio of AvLOX:UtCAT(12.6:4127.3) in E. coli-AvLOX-(rbs3)UtCAT was finally achieved. Under the optimized transformation conditions, pyruvate was produced at a titer of 59.9 g/L and a yield of 90.8% in a substrate fed-batch process, promising an alternative route for the green production of pyruvate.

Apoplastic Hydrogen Peroxide in the Growth Zone of the Maize Primary Root. Increased Levels Differentially Modulate Root Elongation Under Well-Watered and Water-Stressed Conditions.

Reactive oxygen species (ROS) can act as signaling molecules involved in the acclimation of plants to various abiotic and biotic stresses. However, it is not clear how the generalized increases in ROS and downstream signaling events that occur in response to stressful conditions are coordinated to modify plant growth and development. Previous studies of maize (Zea mays L.) primary root growth under water deficit stress showed that cell elongation is maintained in the apical region of the growth zone but progressively inhibited further from the apex, and that the rate of cell production is also decreased. It was observed that apoplastic ROS, particularly hydrogen peroxide (H2O2), increased specifically in the apical region of the growth zone under water stress, resulting at least partly from increased oxalate oxidase activity in this region. To assess the function of the increase in apoplastic H2O2 in root growth regulation, transgenic maize lines constitutively expressing a wheat oxalate oxidase were utilized in combination with kinematic growth analysis to examine effects of increased apoplastic H2O2 on the spatial pattern of cell elongation and on cell production in well-watered and water-stressed roots. Effects of H2O2 removal (via scavenger pretreatment) specifically from the apical region of the growth zone were also assessed. The results show that apoplastic H2O2 positively modulates cell production and root elongation under well-watered conditions, whereas the normal increase in apoplastic H2O2 in water-stressed roots is causally related to down-regulation of cell production and root growth inhibition. The effects on cell production were accompanied by changes in spatial profiles of cell elongation and in the length of the growth zone. However, effects on overall cell elongation, as reflected in final cell lengths, were minor. These results reveal a fundamental role of apoplastic H2O2 in regulating cell production and root elongation in both well-watered and water-stressed conditions.

Physicochemical quality parameters, antibacterial properties and cellular antioxidant activity of Polish buckwheat honey

Buckwheat honey is the darkest Polish honey and has the strongest antibacterial and antioxidant activity; however, the mechanism of this bioactivity remains unknown. To determine the factors responsible for the bioactivity of buckwheat honey, antioxidant power, radical scavenging activity, and total phenolic and flavonoid contents of 20 buckwheat honey samples from southeastern Poland were measured. The antibacterial activity of the honey was studied using 4 bacterial strains. The effect of catalase on the antibacterial action of the honey was determined. Five buckwheat honey samples with different antioxidant and antibacterial activities were selected, and their phenolic profiles were characterized in detail with UPLC-PDA-MS/MS. In vivo experiments showed that these samples protected cells of the yeast Saccharomyces cerevisiae exposed to hydrogen peroxide, which was used as a hydroxyl radical generator. The antibacterial activity was significantly correlated with antioxidant activity and phenolic compounds (p < 0.05). The removal of H2O2 by catalase partially eliminated (30–50%) the bacteriostatic activity of the honeys. The results indicated that among the 13 phenolic compounds identified in buckwheat honeys, only quercetin, rutin, chlorogenic acid and caffeic acid were correlated with its antioxidative and antibacterial activity, which was shown by using Principal Component Analysis (PCA). The protective effect of buckwheat honey resulting from its polyphenols content was confirmed (p < 0.05) against in situ-generated hydroxyl radicals using the S. cerevisiae yeast cells as a biological model.

Oxidative stress induces transcription of telomeric repeat-containing RNA (TERRA) by engaging PKA signaling and cytoskeleton dynamics

Long non-coding RNAs transcribed from telomeres, known as TERRA (telomeric repeat-containing RNA), are associated with telomere and genome stability. TERRA abundance responds to different cell stresses; however, no studies have focused on oxidative stress, condition that damages biomolecules and is involved in aging and disease. Since telomeres are prone to oxidative damage leading to their dysfunction, our objective was to characterize TERRAs and the mechanisms that control their expression. TERRA increased in cells exposed to H2O2 and reverted by antioxidant treatment. TERRAs are also induced in brown adipose tissue of mice exposed to cold, which raises mitochondrial ROS. In cells exposed to H2O2, ChIP showed that chromatin landscape was modified favoring telomere transcription. TERRAs interacted with HP1α/γ, proteins that were found recruited to subtelomeres. Since HP1γ interacts with the transcriptional machinery, TERRAs may stimulate their own expression by recruiting HP1γ to subtelomeres. TERRA induction reverted within 2 h after removal of H2O2 from culture medium, suggesting they have protective functions. This was supported by rapid TERRA induction following a second H2O2 challenge. PKA inhibitors H89 and PKI blocked TERRA increase by H2O2 or IBMX+Forskolin treatment, suggesting PKA signaling regulates TERRA induction. Treatment of cells with drugs that disturb cytoskeleton integrity or growing cells on surfaces of different stiffness known to generate differential cytoskeleton tension also modified TERRA levels and sensitized cells to lower H2O2 concentrations. In summary, we show that TERRAs are induced in response to oxidative stress and are regulated by PKA as well as by changes in cytoskeleton dynamics.

Strengthened antioxidant capacity improves photosynthesis by regulating stomatal aperture and ribulose-1,5-bisphosphate carboxylase/oxygenase activity

ABA is important for plant growth and development; however, it also inhibits photosynthesis by regulating the stomatal aperture and ribulose-1,5-bisphosphate carboxylase/oxygenase activity. Noteworthy, this negative effect can be alleviated by antioxidants including ascorbic acid (AsA) and catalase (CAT), but the underlying mechanism remains unclear. Two rice cultivars, Zhefu802 (recurrent parent) and its near-isogenic line, fgl were selected and planted in a greenhouse with 30/24 °C (day/night) under natural sunlight conditions. Compared to fgl, Zhefu802 had significantly lower net photosynthetic rate (PN) and stomatal conductance (Cond) as well as significantly higher ABA and H2O2 contents. However, AsA and CAT increased PN, Cond, and stomatal aperture, which decreased H2O2 and malondialdehyde (MDA) levels. In this process, AsA and CAT significantly increased the ribulose-1,5-bisphosphate carboxylase activity, while they strongly decreased the ribulose-1,5-bisphosphate oxygenase activity, and finally caused an obvious decrease in the ratio of photorespiration (Pr) to PN. Additionally, AsA and CAT significantly increased the expression levels of RbcS and RbcL genes of leaves, while H2O2 significantly decreased them, especially the RbcS gene. In summary, the removal of H2O2 by AsA and CAT can improve the leaf photosynthesis by alleviating the inhibition on the stomatal conductance and ribulose-1,5-bisphosphate carboxylase capacity caused by ABA.

Diurnal variability, photochemical production and loss processes of hydrogen peroxide in the boundary layer over Europe

Abstract. Hydrogen peroxide (H2O2) plays a significant role in the oxidizing capacity of the atmosphere. It is an efficient oxidant in the liquid phase and serves as a temporary reservoir for the hydroxyl radical (OH), the most important oxidizing agent in the gas phase. Due to its high solubility, removal of H2O2 due to wet and dry deposition is efficient, being a sink of HOx (OH+HO2) radicals. In the continental boundary layer, the H2O2 budget is controlled by photochemistry, transport and deposition processes. Here we use in situ observations of H2O2 and account for chemical source and removal mechanisms to study the interplay between these processes. The data were obtained during five ground-based field campaigns across Europe from 2008 to 2014 and bring together observations in a boreal forest, two mountainous sites in Germany, and coastal sites in Spain and Cyprus. Most campaigns took place in the summer, while the measurements in the south-west of Spain took place in early winter. Diel variations in H2O2 are strongly site-dependent and indicate a significant altitude dependence. While boundary-layer mixing ratios of H2O2 at low-level sites show classical diel cycles with the lowest values in the early morning and maxima around local noon, diel profiles are reversed on mountainous sites due to transport from the nocturnal residual layer and the free troposphere. The concentration of hydrogen peroxide is largely governed by its main precursor, the hydroperoxy radical (HO2), and shows significant anti-correlation with nitrogen oxides (NOx) that remove HO2. A budget calculation indicates that in all campaigns, the noontime photochemical production rate through the self-reaction of HO2 radicals was much larger than photochemical loss due to reaction with OH and photolysis, and that dry deposition is the dominant loss mechanism. Estimated dry deposition velocities varied between approximately 1 and 6 cm s−1, with relatively high values observed during the day in forested regions, indicating enhanced uptake of H2O2 by vegetation. In order to reproduce the change in H2O2 mixing ratios between sunrise and midday, a variable contribution from transport (10 %–100 %) is required to balance net photochemical production and deposition loss. Transport is most likely related to entrainment from the residual layer above the nocturnal boundary layer during the growth of the boundary layer in the morning.

Hyperoxidation of mitochondrial peroxiredoxin limits H2O2‐induced cell death in yeast

Hydrogen peroxide (H2O2) plays important roles in cellular signaling, yet nonetheless is toxic at higher concentrations. Surprisingly, the mechanism(s) of cellular H2O2 toxicity remain poorly understood. Here, we reveal an important role for mitochondrial 1‐Cys peroxiredoxin from budding yeast, Prx1, in regulating H2O2‐induced cell death. We show that Prx1 efficiently transfers oxidative equivalents from H2O2 to the mitochondrial glutathione pool. Deletion of PRX1 abrogates glutathione oxidation and leads to a cytosolic adaptive response involving upregulation of the catalase, Ctt1. Both of these effects contribute to improved cell viability following an acute H2O2 challenge. By replacing PRX1 with natural and engineered peroxiredoxin variants, we could predictably induce widely differing matrix glutathione responses to H2O2. Therefore, we demonstrated a key role for matrix glutathione oxidation in driving H2O2‐induced cell death. Finally, we reveal that hyperoxidation of Prx1 serves as a switch‐off mechanism to limit oxidation of matrix glutathione at high H2O2 concentrations. This enables yeast cells to strike a fine balance between H2O2 removal and limitation of matrix glutathione oxidation.

Decomposition of complexed Pb(II) and subsequent adsorption of Pb(II) with yolk-shell Fe3O4@ hydrous zirconium oxide sphere

Purification of water containing heavy metals that are complexed by organic chelating agents remains a challenging task. In this study, a yolk-shell Fe3O4@hydrous zirconium oxide (Zr(OH)x) sphere sphere (YHZOs) nanomaterial was evaluated for its ability to remove ethylene diamine tetraacetic acid complexed Pb2+ (Pb-EDTA) from aqueous solution. Specifically, it is hypothesized that upon addition of H2O2, the Fe3O4 core of YHZOs served as a Fenton-type catalyst that results in oxidation of the Pb-complexed EDTA, and the Zr(OH)x shell acted as an adsorbent, removing the released Pb2+ from solution. From an aqueous solution containing 0.1 mM Pb-EDTA at pH 5, 0.5 g/L YHZOs, and 20 mM H2O2, TOC reduction and Pb removal were determined to be 65.3% and 89.8%, respectively. HPLC-MS, IC and continuous flow analyzer results identified major intermediates of EDTA decay to be ethylenediaminetriacetate, (ED3A), ethylenediamine-N,N’-diacetate (ED2A), nitrilotriacetate (NTA), iminodiacetate (IDA), ethylenediamine (EDA), acetic acid, formic acid, oxalic acid, ammonia, and nitrate, with the first 5 species having some affinity to remain complexed to Pb2+. The adsorption of Pb2+ onto the Zr(OH)x shells was confirmed by scanning transmission electron microscopy (STEM) with mapping and X-ray photoelectron spectra (XPS). Moreover, the Pb2+-adsorbed YHZOs could be easily recovered due to their magnetic properties, with the Pb2+ rinsed from them at low pH. Indeed, reused for five cycles showed only minor capacity loss. These findings suggest that the removal of chelated Pb2+ from water, and presumably other heavy metals, by yolk-shell Fe3O4@Zr(OH)x may prove to be a useful technology for some contaminated waters.

Organosilica-Based Hollow Mesoporous Bilirubin Nanoparticles for Antioxidation-Activated Self-Protection and Tumor-Specific Deoxygenation-Driven Synergistic Therapy.

A major concern about glucose oxidase (GOx)-mediated cancer starvation therapy is its ability to induce serious oxidative damage to normal tissues through the massive production of H2O2 byproducts in the oxygen-involved glucose decomposition reaction, which may be addressed by using a H2O2 scavenger, known as an antioxidation agent. Surprisingly, H2O2 removal accelerates the aerobic glycometabolism of tumors by activating the H2O2-dependent "redox signaling" pathway of cancer cells. Simultaneous oxygen depletion further aggravates tumor hypoxia to increase the toxicity of a bioreductive prodrug, such as tirapazamine (TPZ), thereby improving the effectiveness of cancer starvation therapy and bioreductive chemotherapy. Herein, a "nitrogen-protected silica template" method is proposed to design a nanoantioxidant called an organosilica-based hollow mesoporous bilirubin nanoparticle (HMBRN), which can act as an excellent nanocarrier to codeliver GOx and TPZ. In addition to efficient removal of H2O2 for self-protection of normal tissues via antioxidation, GOx/TPZ-coloaded HMBRN can also rapidly deplete intratumoral glucose/oxygen to promote a synergistic starvation-enhanced bioreductive chemotherapeutic effect for the substantial suppression of solid tumor growth. Distinct from the simple combination of two treatments, this study introduces antioxidation-activated self-protection nanotechnology for the significant improvement of tumor-specific deoxygenation-driven synergistic treatment efficacy without additional external energy input, thus realizing the renaissance of precise endogenous cancer therapy with negligible side effects.

Co-delivery of therapeutic protein and catalase-mimic nanoparticle using a biocompatible nanocarrier for enhanced therapeutic effect

Therapeutic proteins are indispensable in the treatment of various human diseases. Despite the many benefits of therapeutic proteins, they also exhibit diverse side effects. Therefore, reducing unwanted side effects of therapeutic proteins as well as enhancing their therapeutic efficacy are very important in developing therapeutic proteins. Urate oxidase (UOX) is a therapeutic enzyme that catalyzes the conversion of uric acid (UA) into a soluble metabolite, and it is used clinically for the treatment of hyperuricemia. Since UA degradation by UOX generates H2O2 (a cytotoxic side product), UOX was co-delivered with catalase-mimic nanoparticles (AuNPs) using biocompatible pluronic-based nanocarriers (NCs) to effectively reduce H2O2-associated toxicity in cultured cells and to enhance UA degradation efficiency in vivo. Simple temperature-dependent size changes of NCs allowed co-encapsulation of both UOX and AuNPs at a high loading efficiency without compromising critical properties, resulting in efficient modulation of a mixing ratio of UOX and AuNPs encapsulated in NCs. Co-localizing UOX and AuNPs in the NCs led to enhanced UA degradation and H2O2 removal in vitro, leading to a great reduction in H2O2-associated cytotoxicity compared with UOX alone or a free mixture of UOX and AuNPs. Furthermore, we demonstrated that co-delivery of UOX and AuNPs using NCs significantly improves in vivo UA degradation compared to simple co-injection of free UOX and AuNPs. More broadly, we showed that biocompatible pluronic-based nanocarriers can be used to deliver a target therapeutic protein along with its toxicity-eliminating agent in order to reduce side effects and enhance efficacy.

Degradation of diclofenac by heterogeneous electro-Fenton process using magnetic single-walled carbon nanotubes as a catalyst

Degradation of diclofenac (DCF) from aqueous solution was investigated by the heterogeneous electro-Fenton (EF) process using magnetic single-walled carbon nanotubes (MSWCNTs) as a new catalyst. The effect of parameters including initial pH, current density, initial catalyst concentration, the initial concentration of DCF and air flow rate on the efficiency of DCF removal and electrochemical production of H2O2 were studied. A removal efficiency of 97.8% for DCF and 71.12% for COD was obtained at an initial pH of 5, current density of 20 mA/cm2, MSWCNTs concentration of 80 mg/L, DCF concentration of 10 mg/L, air flow rate of 1 mL/min and reaction time of 120 min. Regarding the removal of DCF and COD, and production of H2O2, the heterogeneous EF process with MSWCNTs catalyst showed higher activity and efficiency than other electro-catalytic degradation systems. The stability tests of MSWCNTs after 5 time application confirmed its performance potential for long-term degradation of DCF in aqueous solutions. Intermediate products such as 2,3-dichlorobenzene and 2,4-dichlorophenol were identified by gas chromatography-mass spectrometry (GC–MS). Based on the identification of reactive species and the intermediate products, a possible mechanism of removal and degradation pathways for DCF was suggested.

IL-1 beta-mediated macrophage-hepatocyte crosstalk upregulates hepcidin under physiological low oxygen levels

In mammals, the iron masterswitch hepcidin efficiently controls iron recycling by the macrophage-liver axis but the exact interplay between macrophages and hepatocytes remains poorly understood. We here study hepcidin response during macrophage differentiation as well as the macrophage-hepatocyte crosstalk and its subsequent effects on hepatocyte hepcidin using an in vitro co-culture model that mimics the physiological liver microenvironment. We show that macrophage differentiation strongly induces hepcidin by 60-fold both in THP1 macrophages and primary isolated monocyte-derived macrophages. Removal of H2O2 by catalase or inhibition of NOX2 efficiently blocked hepcidin induction. After differentiation, macrophage hepcidin accounted for 10% of total hepatocyte hepcidin and did not respond to low oxygen levels. In contrast, co-culture of differentiated macrophages with Huh7 cells significantly induced hepatocyte hepcidin, which was further potentiated under low oxygen levels. Hepatocyte hepcidin was also upregulated when Huh7 cells were solely exposed to macrophage-conditioned hypoxic medium. A cytokine screen identified macrophage secreted IL-1β as major inducer of hepcidin in hepatocytes. In confirmation, treatment of Huh7 cells with the IL-1 receptor antagonist (anakinra) completely blunted macrophage-mediated hepcidin transcription in hepatocytes. Finally, detailed analysis of potentially involved signaling pathways points toward STAT3 and CEBPδ-mediated hepcidin induction independent of IL-6. In conclusion, our study demonstrates a strong NOX2-mediated hepcidin induction during macrophage differentiation. These differentiated macrophages are able to efficiently induce hepatocyte hepcidin mainly through secretion of IL-1β. Our data highlight a hitherto unrecognized role of macrophage-hepatocyte crosstalk for a joint and oxygen-dependent hepcidin production through STAT3 and CEBPδ.

Visual distance readout to display the level of energy generation in paper-based biofuel cells: application to enzymatic sensing of glucose.

Biofuel cells (BFCs) based on anodic oxidation and cathodic oxygen reduction represent an attractive alternative to self-powered devices. A glucose/oxygen BFC is described for monitoring glucose. It is making use of a piece of paper carrying a glucose oxidase (GOx) based bioanode, and a bilirubin oxidase (BilOx) based biocathode. The performance of the BFC is affected by the generation of H2O2, a byproduct of enzymatic glucose oxidation. Therefore, the removal of H2O2 is a crucial step in terms of BFC performance and stability. In addition, direct, unambiguous visual read-out is an ideal way to provide quantitative information. The colorimetric readout system described here is based on the consumption of undesired H2O2 and to convert the extent of energy generation into recognizable variations in color. As the H2O2 travels along the hydrophilic channel by capillary action, the formation of red gold nanoparticles from AuCl4- leads to the appearance of a red bar that provides distance-based information that can be read visually. The multiply readable information (maximum power density of BFC or visible distance) provides further choices for quantification. It also enhances reliability. The self-powered system based on the BFC exhibits excellent performance. Glucose can bedetermined by this method in the 1 to 50mM concentration range. Graphical abstract Schematic presentation of a paper-supported biofuel cell equipped with a visual distance readout to display the level of energy generation in biofuel cells, andits application in sensing of glucose.