Stimulation Of H2O2 Research Articles

Tumor Microenvironment-Responsive Biodegradable Nanomedicine for Self-Enhanced Synergistic Chemo-, Photothermal, and Chemodynamic Therapy.

The nanoscale multidrug codelivery system for synergistic therapy is an effective strategy for tumor treatment. However, the low drug delivery efficiency and poor therapeutic effects limit its application. Here, based on the coordination effect of Artemisinin (Art), quercetin (Qc), and Fe3+, we had constructed a safe and efficient carrier-free hyaluronic acid (HA)-modified Art-Fe-Qc nanoparticles (AFQ@HA NPs) for enhanced chemotherapy/photothermal therapy (PTT)-chemodynamic therapy (CDT) synergistic therapy, which achieved an ultrahigh drug loading efficiency and a multifunction anticancer strategy. The results showed that high drug loading was achieved based on drug coordination self-assembly, with Art and Qc contents of 38.6 and 42.7%, respectively. At the same time, based on the Qc-Fe coordination molecular network, the system had excellent photothermal conversion performance with an efficiency of 57.3% and could effectively inhibit the expression of HSP70, achieving enhanced PTT. Further, under the stimulation of excessive H2O2 and glutathione (GSH) in the tumor microenvironment, the AFQ@HA NPs were continuously degraded, while releasing Art and Fe3+/Fe2+ to achieve iron ion-enhanced CDT. The results of in vitro and in vivo experiments showed that AFQ@HA NPs could achieve chemotherapy-PTT-CDT synergistic therapy in response to tumor microenvironment by passively targeting and actively targeting tumor cells with CD44, demonstrating its excellent targeted antitumor effects.

Real time precisely tracing the fluctuations of mitochondrial SO2 in cells during ferroptosis and tissues using a mitochondrial-immobilized ratiometric fluorescent probe

Mitochondrial sulfur dioxide (SO2) plays important roles in physiological and pathological activities. Unfortunately, it is lack of a reliable tool to precisely visualize the mitochondrial SO2 and elaborate its complicated functions in various cytoactivities. Here we report a mitochondrial-immobilized fluorescent probe PM-Cl consisting of coumarin and benzyl chloride modified benzothiazole, which enables selective visualization of mitochondrial SO2via chemical immobilization. The spectral results demonstrated that probe PM-Cl could respond to SO2 with high selectivity and sensitivity. Co-localization and the fluorescence of cytolysis extraction verified the excellent mitochondrial targeting and anchoring abilities. Due to the chemical immobilization, probe PM-Cl could firmly retain into mitochondria after stimulation of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and H2O2. Significantly, a series of fluorescence images are indicative of capability for detecting the fluctuations of SO2 in mitochondria during ferroptosis. Furthermore, PM-Cl also could visualize SO2 in myocardium and muscle tissues after the stimulation of CCCP. Taken together, probe PM-Cl is a very potential molecular tool for precisely detecting mitochondrial SO2 to explore its complex functions in physiological and pathological activities.

Glycine Enhances Oxidative Stress Tolerance and Biocontrol Efficacy of Sporidiobolus pararoseus against Aspergillus niger Decay of Apples.

Apples are deeply loved by people because of their rich nutritional value, but they are susceptible to rotting. The use of antagonistic yeast is a promising method for controlling postharvest fruit diseases, but biocontrol efficacy of yeast will be weakened in environmental stress. In this study, the effects of glycine (Gly) on the oxidative stress tolerance and the biocontrol efficacy of Sporidiobolus pararoseus (S. pararoseus) against Aspergillus niger (A. niger) are discussed. Under the stimulation of H2O2, the yeast cells treated with Gly (1 mM) showed lower ROS content, less mitochondrial impairment and cellular oxidative damage, and the cell survival rate was significantly higher than Gly-untreated yeast. The yeast cells exposed to Gly significantly increased the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and the content of glutathione (GSH). Notably, Gly-treated yeast cells had better biocontrol efficacy against A. niger in postharvest apples. The lesion diameter and decay incidence were reduced by 17.67 mm and 79.63% compared to the control, respectively, when S. pararoseus was treated with 1 mM Gly. Moreover, Gly-treated yeast increased the antioxidant enzymes activities and their gene expression were up-regulated in apples. These results indicated that 1 mM Gly not only reduced the oxidative damage of yeast, but also induced resistance-related enzymes of apples under oxidative stress, which contributed to enhancing the biocontrol efficacy of S. pararoseus against A. niger in apples.

A synergistic strategy of dual-crosslinking and loading intelligent nanogels for enhancing anti-coagulation, pro-endothelialization and anti-calcification properties in bioprosthetic heart valves.

Currently, glutaraldehyde (GA)-crosslinked bioprosthetic heart valves (BHVs) still do not guarantee good biocompatibility and long-term effective durability for clinical application due to their subacute thrombus, inflammation, calcification, tearing and limited durability. In this study, double-modified xanthan gum (oxidized/vinylated xanthan gum (O2CXG)) was acquired from xanthan gum for subsequent double crosslinking and modification platform construction. Sulfonic acid groups with anticoagulant properties were also introduced through the free radical polymerization of vinyl sulfonate (VS) and vinyl on O2CXG. Taking advantage of the drug-loading function of xanthan gum, the treated pericardium was further loaded with inflammation-triggered dual drug-loaded nanogel (heparin (Hep) and atorvastatin (Ator)). Mechanical properties of O2CXG-crosslinked porcine pericardium (O2CXG-PP) were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Due to the presence of sulfonic acid groups as well as the dual drug release from nanogels under the stimulation of H2O2, the hemocompatibility, anti-inflammatory, pro-endothelialization and anti-calcification properties of the crosslinked pericardium modified with nanogels loaded with Hep and Ator (O2CXG+VS+(Hep+Ator) nanogel-PP) was significantly better than that of GA-crosslinked PP (GA-PP). The collaborative strategy of double crosslinking and sequential release of anticoagulant/endothelium-promoting drugs triggered by inflammation could effectively meet the requirement of enhanced multiple performance and long-term durability of bioprosthetic heart valves and provide a valuable pattern for multi-functionalization of blood contacting materials. STATEMENT OF SIGNIFICANCE: Currently, glutaraldehyde-crosslinked bioprosthetic heart valves (BHVs) are subject to subacute thrombus, inflammation, calcification and tearing, which would not guarantee good biocompatibility and long-term effective durability. We developed a cooperative strategy of double crosslinking and surface modification in which double-modified xanthan gum plays a cornerstone. The mechanical properties of this BHV were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Inflammation-triggered combination delivery of heparin and atorvastatin has been demonstrated to enhance anticoagulation, anti-inflammatory and pro-endothelialization of BHVs by utilizing local inflammatory response. The collaborative strategy could effectively meet the requirement of enhanced multiple performance and long-term durability of BHVs and provide a valuable pattern for the multi-functionalization of blood-contacting materials.

Chemo-Triggered luminescence of sulfur nanoparticles for highly secure information storage

Most of the information storage technologies that rely solely on the luminous signals of specific materials may be cracked and forged. It is always a technical challenge that special “keys” are used to trigger luminescent material for encryption. In this paper, green fluorescent quantum dots (green SQDs) were synthesized by utilizing the corrosion and encapsulation functions of polyethyleneimine (PEI). Green SQDs transform into blue SQDs under the stimulation of H2O2. Stimulus-responsive characterization of green SQDs was used for highly secure message encryption. This work provides a promising application in the field of high-security information storage for chem-triggered luminescent materials.

L-Arginine self-delivery supramolecular nanodrug for NO gas therapy.

NO gas therapy is a supplementary approach for tumor treatment due to the advantages of minimal invasion, little drug resistance, low side effect and amplified efficacy. l-Arginine (L-Arg), a natural NO source with good biocompatibility, can release NO under the stimulation of H2O2 in tumor microenvironment. However, the conventional l-Arg delivery systems via noncovalent loading usually lead to inevitable premature leakage of nano-cargos during blood circulation. In this work, an efficient l-Arg self-delivery supramolecular nanodrug (SDSND) for tumor treatment is demonstrated by combining Mannich reaction and π-π stacking. l-Arg links to (-)-epigallocatechin gallate (EGCG) with the assistance of formaldehyde through Mannich reaction, and then assembles into nanometer-sized particles via π-π stacking. The guanidine group of l-Arg and the phenolic hydroxyl groups of EGCG are preserved in the SDSNDs, which allows for accomplishing gas therapy by provoking tumor cell apoptosis and combining with EGCG to amplify apoptosis, respectively. In addition, the SDSNDs exhibit high biocompatibility and avoid the premature leakage of l-Arg in blood circulation, providing an alternative l-Arg delivery system for NO gas therapy. STATEMENT OF SIGNIFICANCE: NO gas therapy has attracted emerging interest in tumor treatment. However, the controlled NO release and the avoidance of premature leakage of NO donors remain challenging. In this work, L-Arginine (L-Arg) self-delivery supramolecular nanodrug for efficient tumor therapy is demonstrated through the Mannich reaction of L-Arg, (-)-epigallocatechin gallate (EGCG) and formaldehyde. Stimulated by tumor microenvironment, the guanidine groups of L-Arg allow for accomplishing NO release and thus provoking tumor cell apoptosis. The nanodrug also avoids the premature leakage of L-Arg in blood circulation. Moreover, the preserved phenolic hydroxyl groups of EGCG combine with L-Arg to amplify apoptosis. The nanodrug exhibits high biocompatibility and good therapeutic effect, providing an alternative L-Arg delivery system for NO gas therapy.

Establishment of specific age-related macular degeneration relevant gene expression panels using porcine retinal pigment epithelium for assessing fucoidan bioactivity

PurposeAge-related macular degeneration (AMD) is the leading cause of severe vision loss in industrialized nations. Important factors in pathogenesis are oxidative stress, inflammation, and, in the wet form of AMD, angiogenesis. Fucoidans, sulfated polysaccharides from brown algae, may have antioxidant, anti-inflammatory, and antiangiogenic effects. In this study, we established specific gene expression panels for inflammation, oxidative stress and angiogenesis in porcine retinal pigment epithelium (RPE), and investigated the effect of fucoidans on gene expression under different noxious agents. MethodsPrimary porcine RPE cells cultured for at least 14 days were used. Using viability assays with tetrazolium bromide and real-time polymerase chain reaction of marker genes, positive controls were established for appropriate concentrations and exposure times of selected noxious agents (lipopolysaccharide (LPS), H2O2, CoCl2). Three different AMD relevant gene panels specific for porcine RPE for inflammation, oxidative stress, and angiogenesis were established, and the influence of fucoidans (mainly Fucus vesiculosus; FV) on gene expression was investigated. ResultsThe following was shown by gene expression analyses:(1) Inflammation panel: Expression of 18 genes was affected under LPS (three days). Among them, LPS increased genes for interleukin 1 receptor 2, interleukin 8, cyclooxygenase-2 and vascular cell adhesion protein 1 expression which were diminished when FV was present.(2) Oxidative stress panel: Under stimulation of H2O2 (one day) and LPS (one day), expression of a total of 15 genes was affected. LPS induced increase in genes for superoxide dismutase-1, C-X-C motif chemokine 10, and CC chemokine ligand-5 expression was not detected when FV was present.(3) Angiogenesis panel: Under stimulation with CoCl2 (three days) expression of six genes was affected, with the increase of genes for angiopoietin 2, vascular endothelial growth factor receptor-1, and follistatin being diminished when FV was present. ConclusionThree specific gene expression panels for porcine RPE that map genes for three of the major pathological factors of AMD, inflammation, oxidative stress, and angiogenesis, were established. Further, we demonstrated that fucoidans can reduce stress related gene activation in all of these three major pathogenic pathways. This study is another indication that fucoidans can act on different pathomechanisms of AMD simultaneously, which provides further evidence for fucoidans as a possible drug for treatment and prevention of AMD.

Kaempferol promotes melanogenesis and reduces oxidative stress in PIG1 normal human skin melanocytes

Vitiligo is an autoimmune disease characterized by depigmentation. Kaempferol is a flavonoid compound with broad anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effect of kaempferol on melanogenesis in PIG1 normal human skin melanocytes and its response to oxidative stress. The effect of kaempferol on melanin synthesis in PIG1 normal human skin melanocytes was explored by measuring tyrosinase activity, melanin content, mRNA and protein expression of key enzymes and expression of related pathway proteins. The effects of kaempferol pretreatment on cell viability, apoptosis, ROS level and HO-1 protein level under H2 O2 stimulation were explored. When treated with kaempferol, the tyrosinase activity and melanin content of PIG1 cells increased, the mRNA and protein expressions of TYR, TRP1, TRP2 and MITF increased, and the phosphorylation level of ERK1/2 increased. Upon the stimulation of H2 O2 , kaempferol reduced the production of ROS, decreased apoptosis and increased the protein expression of HO-1 in PIG1 cells. In addition, kaempferol inhibited oxidative stress-induced melanin reduction and promoted melanin synthesis in PIG1 cells and protected against H2 O2 -induced oxidative stress damage.

Selenium-decorated biocompatible honeycomb films with redox-switchable surface for controlling cell adhesion/detachment

Hypothesis.Selenium (Se)-containing compound is sensitive to redox stimulation, showing hydrophobic-hydrophilic reversible transition. Introduction of such compound into honeycomb film could confer on it redox-switchable surface wettability, which is expected to control cell adhesion/detachment behavior.Experiments.Didodecyl selenide was designed and mixed with polystyrene to prepare honeycomb films using “breath figure” method. The film microstructures were characterized by scanning electron microscope and atomic force microscopy, and the arrangement of Se atoms in honeycomb film was determined by X-ray photoelectron spectroscopy and energy dispersive spectrometry. The variation of film wettability upon the alternating stimulation of H2O2 and Vc was examined. Then the cell adhesion, proliferation, and controlled detachment on honeycomb films were conducted.Findings.The introduction of didodecyl selenide helps to form ordered honeycomb film, and Se atoms were found to located on the bottom, pore walls, and top surface of the film. The presence of didodecyl selenide not only greatly improves film biocompatibility by enhancing cell thioredoxin reductase activity, but also imparts the film with H2O2–/vitamin C-regulated tunable wettability that controls cell adhesion and detachment. H2O2 treatment produces a hydrophilic surface for cell adhesion and proliferation, whereas the addition of vitamin C generates hydrophobic surfaces and allows cells to detach while remaining alive with high activity.

Synthesis and Evaluation of Reactive Oxygen Species Sensitive Prodrugs of a NAMPT Inhibitor FK866

NAMPT is an attractive target in cancer therapy and numerous NAMPT inhibitors have been developed. However, the clinical activities of NAMPT inhibitors have displayed disappointing results in clinical trials for their dose-limiting toxicities. In this study, reactive oxygen species (ROS)-responsive prodrugs of a NAMPT inhibitor FK866 were designed and synthesized. A short synthesis method was developed to shield the activity of FK866 through a quaternary ammonium connection. Two prodrugs, with boronic acid as a responsive group to ROS, were prepared and one of the prodrugs 122-066 also contained a fluorescence carrier. Both of the prodrugs released the active compound by the treatment of H2O2,, and the biological evaluation showed that they exhibited a higher potency in cells with high levels of ROS. Moreover, prodrug 122-066 had the ability to release FK866 and simultaneously induce the fluorescence activation under the stimulation of H2O2. This method has the potential to improve the therapeutic window of NAMPT inhibitors.

Stimuli-responsive doxorubicin-loading Zr-MOF film for time-ordered tumor therapy and bone regeneration

The recurrence of bone tumors in the early stage and poor osseointegration in the late stage are the main challenges in the clinical treatment of osteosarcoma. Thus, developing a bone implant with time-ordered anti-tumor and osteogenic abilities may be a promising strategy for osteosarcoma therapy. Here, we constructed a NIR and H2O2 dual-responsive Zr-MOF film composed of Zr ions and ferrocene on the titanium and then loaded the anti-tumor drug doxorubicin (DOX) by electrostatic interaction. Under the stimulation of H2O2 in the tumor microenvironment, the Fe2+ in this Zr-MOF film transformed to Fe3+, which could reduce the negative charge of the Zr-MOF to release DOX. Besides, this drug-loading Zr-MOF film possessed good photothermal conversion capability, which enabled the rapid synthetic anti-tumor effect of chemotherapy and photothermal therapy in the initial stage by using NIR irradiation. In vitro results confirmed that the drug-loading Zr-MOF film exhibited good anti-tumor performance against two kinds of human osteosarcoma cells (Saos-2 and 143B cells), which could be further enhanced by using NIR irradiation, and it also showed good anti-tumor properties in vivo. On the other hand, this Zr-MOF film became super hydrophilic after tumor treatment and then promoted the adhesion and the expression of osteogenic genes (ALP, Col-I, TGF-β, and Runx2) of bone cells. This study provides new sight into the design of bone implants with time-ordered tumor therapy and bone regeneration abilities in practical clinical applications.

Neuroprotective Effect of Abelmoschus manihot Flower Extracts against the H2O2-Induced Cytotoxicity, Oxidative Stress and Inflammation in PC12 Cells.

The progression of neurodegenerative diseases is associated with oxidative stress and inflammatory responses. Abelmoschus manihot L. flower (AMf) has been shown to possess excellent antioxidant and anti-inflammatory activities. This study investigated the protective effect of ethanolic extract (AME), water extract (AMW) and supercritical extract (AMS) of AMf on PC12 neuronal cells under hydrogen peroxide (H2O2) stimulation. This study also explored the molecular mechanism underlying the protective effect of AME, which was the best among the three extracts. The experimental results showed that even at a concentration of 500 μg/mL, neither AME nor AMW showed toxic effects on PC12 cells, while AMS caused about 10% cell death. AME has the most protective effect on apoptosis of PC12 cells stimulated with 0.5 mM H2O2. This is evident by the finding when PC12 cells were treated with 500 μg/mL AME; the viability was restored from 58.7% to 80.6% in the Treatment mode (p < 0.001) and from 59.1% to 98.1% in the Prevention mode (p < 0.001). Under the stimulation of H2O2, AME significantly up-regulated the expression of antioxidant enzymes, such as catalase, glutathione peroxidase and superoxide dismutase; promoted the production of the intracellular antioxidant; reduced glutathione; and reduced ROS generation in PC12 cells. When the acute inflammation was induced under the H2O2 stimulation, AME significantly down-regulated the pro-inflammatory cytokines and mediators (e.g., TNF-α, IL-1β, IL-6, COX-2 and iNOS). AME pretreatment could also greatly promote the production of nucleotide excision repair (NER)-related proteins, which were down-regulated by H2O2. This finding indicates that AME could repair DNA damage caused by oxidative stress. Results from this study demonstrate that AME has the potential to delay the onset and progression of oxidative stress-induced neurodegenerative diseases.

Poly (Thioether-Polyesters) Micelles Encapsulation Induces ROS-Triggered Targeted Release of Tangeretin

Tangeretin (Tan) possesses great anti-oxidation and anti-inflammation bioactivities; however, it is accompanied by poor water solubility, which leads to inefficient cellular internalization. To address this issue, a reactive oxygen species (ROS)-triggered poly (thioether-polyesters) micelle (PDHP, PEG-DTT) was designed and prepared via self-assembly, which consisted of poly (thioether-polyesters) as the hydrophilic shell, and the drug Tan as the hydrophobic inner core. The micelles (Tan@ PDHP), with a 63.15% loading efficiency of Tan, showed negligible cytotoxicity, high stability in phosphate-buffered saline buffer (pH = 7.4), and continuous release of Tan with the stimulation of H2O2. In addition, this Tan loading micelle was more efficient in responding to the formation of ROS in the lipopolysaccharide-stimulated RAW264.7 cells compared to that of the free Tan. In short, the strategy of encapsulating the low solubility Tan in ROS-triggered poly (thioether-polyesters) micelles provides an effective assay of enhancing Tan's antioxidative activity.

Calycosin Alleviates Oxidative Injury in Spinal Astrocytes by Regulating the GP130/JAK/STAT Pathway

Spinal injury is a complicated disease and is reported to be associated with damages on spinal astrocytes induced by oxidative injury. Astragali Radi, a famous traditional Chinese medicine, is reported to have promising efficacy in protecting injuries in the central nervous system. This study aims to investigate the effect of calycosin, an isoflavone phytoestrogens isolated from Astragali Radi, on oxidative injury in spinal astrocytes induced by H2O2 and the underlying mechanism. Primary rat spinal astrocytes were pretreated with 5, 10, and 20 μM calycosin and subjected to H2O2 treatment for 24 h to establish an oxidative injury model. Cell viability was detected using the CCK-8 assay to screen the optimized concentration of calycosin. Flow cytometry was used to evaluate the apoptotic rate and cell cycle. The expression level of Brdu was visualized using the immunofluorescence assay. Western blotting was used to measure the expression levels of p-JAK2, p-STAT3, p-AKT, GP130, and IL-6 in spinal astrocytes. We found that proliferation was inhibited and that apoptosis was induced by the stimulation of H2O2. The expression levels of p-JAK2, p-STAT3, p-AKT, GP130, and IL-6 were significantly elevated in H2O2-treated astrocytes. After the treatment of calycosin, proliferation was facilitated, and apoptosis was suppressed. These phenomena were accompanied by the downregulation of p-JAK2, p-STAT3, p-AKT, GP130, and IL-6, which were abolished by the co-administration of PI3K (ly294002) or STAT3 (stattic) inhibitor. Overall, calycosin alleviated oxidative injury in spinal astrocytes by mediating the GP130/JAK/STAT pathway.

Inducible expression of heat shock protein 20 protects airway epithelial cells against oxidative injury involving the Nrf2-NQO-1 pathway

BackgroundHeat shock protein (HSP) 20 is a molecular chaperone that exerts multiple protective functions in various kinds of tissues. However, the expression of HSP20 and its specific functions in airway epithelial cells (AECs) remain elusive.ResultsIn current study, we first confirmed the inducible expression of HSP20 in mouse AECs and in a human bronchial epithelial cell line BEAS-2B cells, under different oxidant stressors. Then by establishing a HSP20-abundant mouse model with repeated low-level-ozone exposures and stimulating this model with a single high-level ozone exposure, we found that the HSP20 abundance along with its enhanced phosphorylation potentially contributed to the alleviation of oxidative injuries, evidenced by the decreases in the bodyweight reduction, the BAL neutrophil accumulation, the AECs shedding, and the BAL concentrations of albumin and E-cadherin. The biological function of HSP20 and its molecular mechanisms were further investigated in BEAS-2B cells that were transfected with HSP20-, unphosphorylatable HSP20(Ala) or empty vector plasmids prior to the stimulation of H2O2, of which its oxidant capacity has been proved to be similar with those of ozone in an air–liquid culture system. We found that the H2O2-induced intracellular ROS level and the early cell apoptosis were attenuated in the HSP20- but not HSP20(Ala)- transfected cells. The intracellular expression of NQO-1 (mRNA and protein) and the intranuclear content of Nrf2 were significantly increased in the HSP20- transfected cells but not in the HSP20(Ala)- and empty vector-transfected cells after the stimulation of H2O2.ConclusionsThe inducible expression of HSP20 in AECs by oxidative stress exerts protective roles against oxidative damages, which may involve the activation of the Nrf2-NQO-1 pathway.

Polymer-Encapsulated Cobalt/Gold Bimetallic Nanoclusters as Stimuli-Responsive Chemiluminescent Nanoprobes for Reactive Oxygen Species.

A stimuli-responsive chemiluminescent nanocomposite was developed based on bimetallic nanoclusters encapsulated in a reactive oxygen species (ROS)-responsive polymer for a highly sensitive determination of ROS (i.e., H2O2) in biological samples. Cobalt/gold bimetallic nanoclusters (GSH@Co-AuNCs) were synthesized using glutathione (GSH) as a reducing-cum-protecting reagent. The GSH-coated nanoclusters were covalently bound to N-(4-aminobutyl)-N-ethylisoluminol (ABEI) to form the GSH@Co-AuNCs-ABEI, which was further encapsulated in polymeric ROS-sensitive boronic ester modified dextran (Oxi-Dex) nanospheres through hydrophobic interactions. The stimulation of H2O2, as a model ROS, led to a sustainable structural cleavage of the Co-AuNCs-ABEI@Oxi-Dex nanocomposites and release of internal GSH@Co-AuNCs-ABEI, accompanied by intense chemiluminescence (CL). On this basis, an enzyme-free and reagent-free CL sensor was developed for a highly sensitive and selective determination of H2O2 with a detection limit of 35.8 pM in biological samples. It is of great application potential for the determination of ROS related to various diseases.

Ratiometric Fluorescent Nanohybrid for Noninvasive and Visual Monitoring of Sweat Glucose.

Noninvasive and visual monitoring of glucose is highly desirable for diabetes diagnostics and long-term home-based health management. Owing to the correlation of the glucose level between blood and sweat, on-body sweat glucose detection provides potential for noninvasive healthcare but is highly challenging. Herein, we for the first time demonstrate a wearable skin pad based on the ratiometric fluorescent nanohybrid, which can realize noninvasive and visual monitoring of sweat glucose. Luminescent porous silicon (PSi) particles, which have a porous structure and oxidation-responsive photoluminescence decay, are chosen to load (adsorb or entrap) carbon quantum dots (CQDs) for the construction of the dual fluorescence nanohybrid. Bimetallic (Au and Ag) nanoparticles (BiM) are also co-decorated on the PSi particle to improve detection sensitivity by enhancing PSi's initial fluorescence and oxidation kinetics. Owing to the efficient fluorescence resonance energy transfer effect, BiM-CQDs@PSi initially exhibits PSi's red fluorescence with complete quenching of CQDs's blue fluorescence. The oxidation of PSi triggered by hydrogen peroxide (H2O2) weakens the FRET effect and decays PSi's fluorescence, causing ratiometric fluorescence to change from red (PSi) to blue (CQDs). A wearable skin pad is easily fabricated by co-immobilization of BiM-CQDs@PSi and glucose oxidase (GOX) in a transparent and biocompatible chitosan film supported by an adhesive polyurethane membrane. When the skin pad is attached on the body, the same ratiometric fluorescence transition (red → blue) is observed upon the stimulation of H2O2 generated in GOX-catalyzed oxidation of sweat glucose. Based on the strong correlation between the ratio of the fluorescence change and sweat glucose level, clinical tests toward diabetics and healthy volunteers can clearly indicate hyperglycemia.

A hydrogen peroxide responsive prodrug of Keap1-Nrf2 inhibitor for improving oral absorption and selective activation in inflammatory conditions

Transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), control the redox and metabolic homeostasis and oxidative stress. Inhibitors of Keap1-Nrf2 interaction are promising in oxidative stress related inflammatory diseases but now hit hurdles. By utilizing thiazolidinone moiety to shield the key carboxyl pharmacophore in Keap1-Nrf2 inhibitor, a hydrogen peroxide (H2O2)-responsive prodrug pro2 was developed. The prodrug modification improved the physicochemical properties and cell membrane permeability of the parent drug. Pro2 was stable and stayed inactive under various physiological conditions, while became active by stimulation of H2O2 or inflammation derived reactive oxygen species. Moreover, pro2 exhibited proper pharmacokinetic profile suitable for oral administration and enhanced anti-inflammatory efficiency in vivo. Thus, this novel prodrug approach may not only provide an important advance in the therapy of chronic inflammatory diseases with high level of H2O2, but also offer a fresh solution to improve the drug-like and selectivity issues of Keap1-Nrf2 inhibitors.

MicroRNA-103 Protects Coronary Artery Endothelial Cells against H2O2-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways.

Endothelial cell damage caused by oxidative stress is widely considered to be a triggering event in atherosclerosis (AS). However, the specific effect elicited by autophagy in endothelial cells undergoing oxidative stress remains controversial, especially during end-stage autophagy. The inhibition of end-stage autophagy has been reported to increase cell pyroptosis and contribute to endothelial damage. Several studies have shown that microRNA-103 is involved in end-stage autophagy; however, its specific mechanism of action is not yet characterized. In this study, we addressed the regulatory role of miR-103 in autophagy during oxidative stress of endothelial cells. Hydrogen peroxide (H2O2) treatment was used as an in vitro model of oxidative stress. MTS and ROS levels were measured to evaluate cell activity. qRT-PCR was used to detect the expression of miR-103. Autophagy was examined using western blot, immunofluorescence staining, and electron microscopy, while western blot analysis detected pyroptosis-related proteins. Results show that miR-103 expression decreased under oxidative stress. Further, miR-103 repressed transcription of Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3). The oxidative stress caused by H2O2 caused cell damage from 2 hours (P < 0.05) and increased the level of intracellular reactive oxygen species (P < 0.05); at the same time, the damage could be further aggravated by the stimulation of bafA1 (P < 0.05). Under the stimulation of H2O2, the expression of miR-103 decreased (P < 0.05). However, high expression of miR-103 could reduce the accumulation of LC3II and P62 (P < 0.05) by inhibiting the downstream target gene Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3), thus reducing the occurrence of cell pyroptosis (P < 0.05). This process could be blocked by end-stage autophagy inhibitor bafA1 (P < 0.05), which further indicated that miR-103 affected cell injury by autophagy. On the contrary, the low expression of miR-103 promoted the accumulation of autophagy protein and increased the occurrence of pyroptosis (P < 0.05). In conclusion, inhibition of miR-103 restrained end-stage of autophagy by regulating BNIP3, thus changing the occurrence of cell pyroptosis.

Antioxidant Activity Evaluation of Dietary Flavonoid Hyperoside Using Saccharomyces Cerevisiae as a Model.

Oxidative stress leads to various diseases, including diabetes, cardiovascular diseases, neurodegenerative diseases, and even cancer. The dietary flavonol glycoside, hyperoside (quercetin-3-O-galactoside), exerts health benefits by preventing oxidative damage. To further understand its antioxidative defence mechanisms, we systemically investigated the regulation of hyperoside on oxidative damage induced by hydrogen peroxide, carbon tetrachloride, and cadmium in Saccharomyces cerevisiae. Hyperoside significantly increased cell viability, decreased lipid peroxidation, and lowered intracellular reactive oxygen species (ROS) levels in the wild-type strain (WT) and mutants gtt1∆ and gtt2∆. However, the strain with ctt1∆ showed variable cell viability and intracellular ROS-scavenging ability in response to the hyperoside treatment upon the stimulation of H2O2 and CCl4. In addition, hyperoside did not confer viability tolerance or intercellular ROS in CdSO4-induced stress to strains of sod1∆ and gsh1∆. The results suggest that the antioxidative reactions of hyperoside in S. cerevisiae depend on the intercellular ROS detoxification system.