Glucose oxidase and ruthenium nanorods-embedded self-healing polyvinyl alcohol/polyethylene imine hydrogel for simultaneous photothermal/photodynamic/starvation therapy and skin reconstruction.

Tumor recurrence and wound healing represent significant burdens for tumor patients after the surgical removal of melanomas. Wound dressings with wound healing and anticancer therapeutic abilities could help to solve these issues. Thus, a hybrid hydrogel made of polyvinyl alcohol (PVA) and polyethylene imine (PEI) was prepared by cross-linking imine bond and boronic acid bond. This hydrogel was loaded with ruthenium nanorods (Ru NRs) and glucose oxidase (GOx) and named as nanocomposite hydrogel (Ru/GOx@Hydrogel), exhibiting remarkable photothermal/photodynamic/starvation antitumor therapy and wound repair abilities. Ru NRs are bifunctional phototherapeutic agents that simultaneously exhibit intrinsic photothermal and photodynamic functions. Three-dimensional composite hydrogel loaded with GOx can also consume glucose in the presence of O2 during tumor starvation therapy. Near-infrared (NIR) light-triggered hyperthermia can not only promote the consumption of glucose, but also facilitate the ablation of residual cancer cells. The antitumor effect of the Ru/GOx@Hydrogel resulted in significant improvements, compared to those observed with either phototherapy or starvation therapy alone. Additionally, the postoperative wound was substantially healed after treatment with Ru/GOx@Hydrogel and NIR irradiation. Therefore, the Ru/GOx@Hydrogel can be used as a multi-stimulus-responsive nanoplatform that could facilitate on-demand controlled drug release, and be used as a promising postoperative adjuvant in combination therapy.

Electrochemical Detection of ompA Gene of C. sakazakii Based on Glucose-Oxidase-Mimicking Nanotags of Gold-Nanoparticles-Doped Copper Metal-organic Frameworks.

The present work developed an electrochemical genosensor for the detection of virulence outer membrane protein A (ompA, tDNA) gene of Cronobacter sakazakii (C. sakazakii) by exploiting the excellent glucose-oxidase-mimicking activity of copper Metal-organic frameworks (Cu-MOF) doped with gold nanoparticle (AuNPs). The signal nanotags of signal probes (sDNA) that biofunctionalized AuNPs@Cu-MOF (sDNA-AuNPs@Cu-MOF) were designed using an Au-S bond. The biosensor was prepared by immobilization capture probes (cDNA) onto an electrodeposited AuNPs-modified glassy carbon electrode (GCE). AuNPs@Cu-MOF was introduced onto the surface of the GCE via a hybridization reaction between cDNA and tDNA, as well as tDNA and sDNA. Due to the enhanced oxidase-mimicking activity of AuNPs@Cu-MOF to glucose, the biosensor gave a linear range of 1.0 × 10-15 to 1.0 × 10-9 mol L-1 to tDNA with a detection limit (LOD) of 0.42 fmol L-1 under optimized conditions using differential pulse voltammetry measurement (DPV). It can be applied in the direct detection of ompA gene segments in total DNA extracts from C. sakazakii with a broad linear range of 5.4-5.4 × 105 CFU mL-1 and a LOD of 0.35 CFU mL-1. The biosensor showed good selectivity, fabricating reproducibility and storage stability, and can be used for the detection of ompA gene segments in real samples with recovery between 87.5% and 107.3%.

Proton pump inhibitor-enhanced nanocatalytic ferroptosis induction for stimuli-responsive dual-modal molecular imaging guided cancer radiosensitization.

Although radiotherapeutic efficiency has been revealed to be positively correlated with ferroptosis, the neutral/alkaline cytoplasm pH value of tumor cells remains an intrinsic challenge for efficient Fenton/Fenton-like reaction-based ferroptosis induction. Herein, PEGylated hollow mesoporous organosilica nanotheranostics (HMON)-GOx@MnO2 nanoparticles (HGMP NPs) were designed as a ferroptosis inducer, which could specifically release Mn2+ in tumor cells to activate the Fenton-like reaction for ferroptosis induction. Proton pump inhibitors (PPIs) were synchronously administered for cytoplasm pH level regulation by inhibiting V-H+-ATPases activity, enhancing Fenton-like reaction-based ferroptosis induction. Moreover, reactive oxygen species production was facilitated via the glucose oxidase triggered cascade catalytic reaction by utilizing intracellular ß-D-glucose for H2O2 self-supply and generation of additional cytoplasm H+. The PPI enhanced ferroptosis inducing nanosystem effectively inhibited tumor growth both in vitro and in vivo for tumor-specific ferroptosis induction and radiotherapy sensitization, suggesting that PPI administration could be an efficient adjuvant to reinforce Fenton/Fenton-like reaction-based ferroptosis induction for radiosensitization. STATEMENT OF SIGNIFICANCE: The cytoplasm pH value of tumor cells is typically neutral to alkaline, which is higher than that of the Fenton/Fenton-like reaction desired acidic environments, hindering its efficiency. In this study, PEGylated hollow mesoporous organosilica nanotheranostics (HMON)-GOx@MnO2 nanoparticles were synthesized as a ferroptosis inducer, which could specifically release Mn2+ via depleting glutathione and then activate the Fenton-like reaction in the tumor microenvironment. The glucose oxidase was applied for H2O2 self-supply and addition of cytoplasm H+ to further boost the Fenton-like reaction. We found that proton pump inhibitors (PPIs) increased intracellular acidification by inhibiting the activity of V-H+-ATPases to enhance the Fenton reaction-based ferroptosis induction, suggesting PPIs administration could be a feasible strategy to reinforce ferroptosis induction for radiosensitization.

Multifunctional gold nanorods in low-temperature photothermal interactions for combined tumor starvation and RNA interference therapy.

Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metastasis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to practical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation therapy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues. Evidence shows that B7-H3, a type I transmembrane glycoprotein molecule, plays essential roles in growth, metastasis, and drug resistance. By initiating the downregulation of B7-H3 by siRNA, siRNA-GOx/GNR@HA NPs may promote the effectiveness of treatment. By targeting cluster of differentiation 44 (CD44) and depleting B7-H3 and HSPs sequentially, siRNA-GOx/GNR@HA NPs showed 12.9-fold higher lung distribution than siRNA-GOx/GNR NPs. Furthermore, 50% of A549-bearing mice in the siRNA-GOx/GNR NPs group survived over 50 days. Overall, this low-temperature phototherapeutic nanosystem provides an appropriate strategy for eliminating cancer with high treatment effectiveness and minimal systemic toxicity. STATEMENT OF SIGNIFICANCE: To realize efficient tumor ablation under mild low-temperature (42-45 â„ƒ) and RNA interference simultaneously, here we developed a multifunctional gold nanorod (GNR)-based nanosystem (siRNA-GOx/GNR@HA NPs). This nanoplatform can significantly inhibit tumor cell proliferation and induce cell apoptosis by downregulation of HSP90α, HSP70, B7-H3, p-AKT, and p-ERK and upregulation of cleaved caspase-9 at mild low-temperature due to its superior tumor homing ability and the combined effect of photothermal effect, glucose deprivation-initiated tumor starvation, and B7-H3 gene silence effect. It is believed that this multifunctional low-temperature photothermal nanosystem with efficient and specific anticancer properties, shows a potential application in clinical tumor treatment.

Queen Caging and Oxalic Acid Treatment: Combined Effect on Vitellogenin Content and Enzyme Activities in the First Post-Treatment Workers and Drones, Apis mellifera L.

Varroa destructor is a mite causing serious damage to western honey bees. Managed colonies require artificial varroa control, which may be best obtained by combining mechanical and chemical methods. This study explored the possible effects of the combination of queen caging and oxalic acid treatment on the immune system (glucose oxidase, phenoloxidase, and vitellogenin) and antioxidant enzymes (superoxide dismutase, catalase, and glutathione S transferase) of first post-treatment generation drones and workers (newly emerged, nurses, and foragers). The combination of queen caging and oxalic acid treatment caused a decrease in glucose oxidase activity only in drones. This could cause issues of cuticular sclerotization, making a drone prone to bite injuries, dehydration, and pathogens. No differences in phenoloxidase activity were recorded in both post-treatment drones and workers generation. Among worker bees, the treatment determined a lower vitellogenin content in newly emerged bees while the result was higher in nurse bees. However, the treatment did not significantly affect the antioxidant enzymes activity in either drones or workers. The results obtained in this investigation suggest that the combined anti-varroa treatments had no negative effects on oxidative stress in the first post-treatment generation bees, while effects did occur on the immune system. Further investigations on the potential effects of glucose oxidase decrease in drones and vitellogenin content variation in workers are desirable.

Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification.

Ferroptosis has been considered as a promising pathway to overcome apoptosis-induced tumor chemoresistance. However, the antitumor efficacy of ferroptosis-inducing agents is still limited because of the complexity and diversity of tumor microenvironments. Herein, we demonstrate a triple ferroptosis amplification strategy for tumor therapy by associating iron-based nanocarriers, ferroptosis molecular drugs, and H2O2-producing enzymes. Fe(III)-Shikonin (FeShik) metal-polyphenol-coordinated networks are employed to load a ferroptosis inducer of sorafenib (SRF) inside and glucose oxidase (GOx) outside, thus producing SRF@FeShik-GOx supramolecular nanomedicines (SNs). After delivering into glutathione (GSH)-overexpressed tumor cells, FeShik will disassemble and release Fe2+ to induce cell death via ferroptosis. At the same time, GOx executes its catalytic activity to produce an acid environment and plenty of H2O2 for stimulating •OH generation via the Fenton reaction. Moreover, SRF will suppress the biosynthesis of GSH by inhibiting system Xc-, further deactivating the enzymatic activity of glutathione peroxidase 4 (GPX4). Up-regulation of the oxidative stress level and down-regulation of GPX4 expression can dramatically accelerate the accumulation of lethal lipid peroxides, leading to ferroptosis amplification of tumor cells. The current strategy that utilizes ferroptosis-inducing agents as both nanocarriers and cargoes provides a pathway to enhance the efficacy of ferroptosis-based tumor therapy.

Antineoplastic Enzyme as Drug Carrier with Activatable Catalytic Activity for Efficient Combined Therapy.

The delivery of glucose oxidase (GOx) requires extra carriers, which suffers from early leakage and exposure of GOx. These issues will be of less concern if GOx itself acts as a drug carrier. However, the catalytic activity of GOx in the blood still needs to be inhibited. Herein, we found that GOx could self-assemble with hydrophobic molecules into uniform and stable nanoparticles (NPs), including sorafenib, 4'-(amino-methyl phenyl)-2,2' : 6',2''-terpyridine modified cyanin and paclitaxel. The catalytic activity of GOx in NPs was significantly inhibited due to the binding of small molecules with its hydrophobic pockets. After dissociation in the tumor acidic microenvironment, the enzyme activity of GOx could be largely recovered. This acidity-triggered "OFF-to-ON" process ensured safe intravenous administration of GOx-based NPs. In vivo experiments showed that the combined starvation therapy and ferroptosis/photothermal therapy/chemotherapy effectively inhibited 4T1 breast tumor growth.

CuS NP-based nanocomposite with photothermal and augmented-photodynamic activity for magnetic resonance imaging-guided tumor synergistic therapy.

Although many treatments have been developed for oncotherapy, the lack of effective imaging guidance in the therapeutic process is still an urgent problem to be solved. In this study, magnetic resonance contrast agent (Gd) chelated on CuS nanoparticles and glucose oxidase (GOx) were coloaded into mesoporous silica nanoparticles (MSNs) to form GOx-Gd-CuS@MSNs, in which the Gd provided magnetic resonance imaging (MRI) for therapeutic process monitor while GOx could catalyze the generation of H2O2 to enhance the photodynamic therapy (PDT). The in vitro results show that under near-infrared (NIR) laser irradiation (2 W·cm-2, 5 min), temperature rapidly increased by approximately 30 °C for the accumulation of heat. At the same time, GOx on GOx-Gd-CuS@MSNs effectively consumed glucose to produce a large amount of H2O2, which was used to augment PDT through producing highly toxic hydroxyl radicals (·OH) and singlet oxygen (1O2). The photothermal and augmented-photodynamic could induce apoptosis and death of tumor cells. More importantly, the study found that GOx-Gd-CuS@MSNs had MRI performance, which provided imaging guidance during the treatment process, and it can monitor the diffusion of water molecules in the tumor tissue during the treatment and microcirculation perfusion of capillary network. These results indicate that the nanomaterial produced significant synergistic therapeutic effects through photothermal and photodynamic forces, meanwhile showed excellent spatial resolution and deep tissue penetration in imaging.

Engineered Organosilica Hybrid Micelles for Photothermal-enhanced Starvation Cancer Therapy.

Glucose oxidase (GOD)-based starvation therapy (ST), which inhibits the growth and proliferation of cancer cells by consuming glucose, has attracted intensive attention as an emerging non-invasive method for fighting cancers. However, the enzyme activity of GOD is greatly limited in vivo because of its optimal catalytic activity in the temperature range of 43-60 °C. Herein, a photothermal-enhanced starvation strategy is developed based on our engineered organosilica hybrid micelles (TiO2-x @POMs-GOD), in which the fluoride-doped TiO2-x with photothermal properties is encapsulated in the cores of organosilica cross-linked micelles and GOD is immobilized on the carboxyl groups of PAA segments. With its internalization by cancer cells, the conjugated GOD can effectively deplete glucose to achieve the ST effect, which can be remarkably enhanced by the loaded fluoride-doped TiO2-x with NIR laser irradiation, thus cooperatively contributing to the efficient treatment of TiO2-x @POMs-GOD on various cancer cells. This suggests great potential for TiO2-x @POMs-GOD in photothermal-enhanced ST in vivo.

Development of a Thin-Layer Chromatography-Enzymatic Test Combination Method for the Isolation of α-Glucosidase Inhibitors From Thymelaea hirsuta.

A rapid, easy and simple method for the isolation and purification of α-glucosidase inhibitors of the ethyl acetate extract of Thymelaea hirsuta (EaTh) by a combination of thin layer chromatography (TLC) and enzymatic test has been developed. EaTh was demonstrated previously a potent α-glucosidase inhibitory effect. In this study, we developed a simple TLC-enzymatic test (TLC/EZ) combination to isolate α-glucosidase inhibitors present in EaTh.EaTh was extracted by Soxhlet from Thymelaea hirsuta (T. hirsuta). The EaTh was separated on a silica gel column and then on a TLC plate. After TLC separation, the TLC/EZ combination method was applied. α-glucosidase inhibitors were detected directly in the TLC plate using the glucose oxidase peroxidase method (GOD-POD). A good detection of active compounds was obtained in the TLC favoring the TLC/EZ method. Active compounds were then characterized using high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. The main α-glucosidase inhibitors present in EaTh have a molecular ion [M + H]+ at m/z = 543. This proposed method is suitable for a reliable isolation and purification of α-glucosidase inhibitors present in EaTh. It could be proposed as an interesting alternative of the classical method for the isolation and purification of α-glucosidase inhibitors in plant extracts.

Mild-Temperature Photothermal Effect Enhanced by Functional Conjugated Polymer Nanoparticles through Enzyme-Mediated Starvation.

Mild-temperature photothermal therapy (PTT) is being extensively explored because it causes less injury to normal cells. However, the effect of mild-temperature PTT is decreased because of heat shock protein (HSP) overexpression. To solve this problem, we designed functional conjugated polymer nanoparticles (CPNs-G) that enhance the mild-temperature photothermal effect. Upon near-infrared (NIR) light irradiation, CPNs-G generate local heat to realize the photothermal effect. Meanwhile, the increased temperature enhances the catalytic activity of GOx, thus impeding the generation of adenosine triphosphate (ATP) and inhibiting HSP expression. Therefore, this work provides a strategy for overcoming thermoresistance through an enzyme-mediated starvation effect regulated by NIR light.

FC-BBR/IND-induced glucose oxidase nanodrugs for targeted combination therapy.

Targeted therapy from cells to mitochondria can improve the bioavailability and therapeutic effects of drugs. Combination therapy by combining two or more therapeutic methods comes to be seen a hopeful strategy to overcome the emergence of resistance. Ferrocene (FC) derivatives of the sandwich structure can not only directly inhibit the proliferation of cancer cells but also catalyze the Fenton reaction to enhance chemodynamic therapy. Berberine (BBR) is a Chinese herbal extract with mitochondria-targeted anticancer activity. In our work, glucose oxidase (GOD) was induced to self-assemble by ferrocene-berberine conjugate (FC-BBR) and indomethacin (IND), which was then encapsulated by hyaluronic acid (HA) and formed nanodrugs (FC-BBR/IND@GOD@HA NPs). Molecular simulation results showed that the drugs could be bound to multiple sites of GOD and induce its self-assembly. The prepared nanoassembly could inhibit the proliferation and induce the apoptosis of HepG2 cells, which might be the result of targeted chemodynamic therapy and starvation therapy. Moreover, the FC-BBR/IND@GOD@HA NPs could also promote the production of reactive oxygen species and the loss of mitochondrial membrane potential and block the cells in S phase. More importantly, it could inhibit the movement and migration of cancer cells, which gave it the potential to prevent tumor metastasis.

Effect of glucose oxidase treatment on the aroma qualities and release of cooked off-odor components from heat-treated Hami melon juice.

Melon juice produces strong cooked off-odors during heat processing, leading to serious deterioration of aroma quality. In this work, the aroma quality of melon juice, the changes in GOD reaction products, and the interactions of reaction products and cooked off-odor components were analyzed by sensory evaluation, gas chromatography-mass spectrometry/olfactory, ultraperformance liquid chromatography-triple quadrupole mass spectrometry, and isothermal titration calorimetry to study the effect mechanism of glucose oxidase (GOD) on the release of cooked off-odor components from heat-treated melon juice. The results showed that GOD treatment improved the aroma quality mainly by controlling off-odor attributes and maintaining characteristic odor attributes. This was because the reaction products (hydrogen peroxide and gluconic acid) of GOD treatment inhibited the release of cooked off-odor components from heat-treated melon juice through oxidation and hydrophobic effects. Furthermore, these products reduced the loss of characteristic odor compounds by restraining Maillard, degradation, and oxidation reactions during heat processing.

Preliminary study on alleviation of heat-induced intestinal inflammation through compensatory effects of glucose oxidase.

1. The influence of glucose oxidase (GOD) supplementation on growth, gut inflammation and its compensatory effects in broilers was investigated before and after heat stress.2. Before heat stress, one-day-old broilers were divided into two groups: the control (CON) and GOD (100 g/t complete feed) groups. On d 21, the CON group was equally divided into CON1 and CON2 groups, and heat stress (35°C) was applied to the CON2 and GOD groups for 8 h/day to the end of the study, d 27 of age. The chickens were either killed before heat stress and 2 d after heat stress for the determination of cytokines in the liver and ileum, serum antioxidant enzymes and ileal microbiota. Growth performance was determined before and 7 d after heat stress.3. The GOD decreased Clostridiales and Enterobacteriaceae families of bacteria and increased ileal nuclear factor-κB, interleukin-1ß, and interferon-γ (P < 0.05) before heat stress. The broilers exhibited compensatory effects, including increases in ileal sirtuin-1, heat shock protein 70 expression, liver nuclear factor erythroid 2-related factor 2 content, serum total antioxidant capacity and glutathione peroxidase level (P < 0.05). At 2 d after heat stress, inflammatory factors were increased in both the CON2 and GOD groups, but the levels were lower in the GOD than CON2 (P < 0.05). On d 7 after heat stress, GOS alleviated heat stress induced growth retardation (P < 0.05).4. These data suggested that GOD supplementation in broiler diets before heat stress stimulated intestinal oxidative stress and produced a compensatory response, which prevented a rapid increase in intestinal inflammatory factors and helped to maintain growth performance under heat stress.

Sensitive silica-alumina modified capacitive non-Faradaic glucose sensor for gestational diabetes.

A highly sensitive silica-alumina (Si-Al)-modified capacitive non-Faradaic glucose biosensor was introduced to monitor gestational diabetes. Glucose oxidase (GOx) was attached to the Si-Al electrode surface as the probe through amine-modification followed by glutaraldehyde premixed GOx as aldehyde-amine chemistry. This Si-Al (∼50 nm) modified electrode surface has increased the current flow upon binding of GOx with glucose. Capacitance values were increased by increasing the glucose concentrations. A mean capacitance value was plotted and the detection limit was found as 0.03 mg/mL with the regression coefficient value, R² = 0.9782 [y = 0.8391x + 1.338] on the linear range between 0.03 and 1 mg/mL. Further, a biofouling experiment with fructose and galactose did not increase the capacitance, indicating the specific glucose detection. This Si-Al-modified capacitance sensor detects a lower level of glucose presence and helps in monitoring gestational diabetes.

Dietary supplementation of Aspergillus niger-expressed glucose oxidase ameliorates weaning stress and improves growth performance in weaning pigs.

Weaning is one of the most stressful events in the pig's life, which disrupts physiological balance and leads to oxidative stress. It is reported that glucose oxidase supplementation could alleviate oxidative stress in animals by increasing the concentration of antioxidant enzymes in vivo. The purpose of this study was to evaluate the effects of dietary supplementation of Aspergillus niger-expressed glucose oxidase (AN-GOX) on growth performance, nutrient digestibility, faecal microbiota, faecal gas emission and serum antioxidant enzyme parameters in weaning pigs. A total of 120 21-day-old weaning pigs [(Yorkshire ×Landrace) × Duroc] with an initial body weight of 6.54 ± 0.55 kg were used in a 21-day experiment (phase 1, days 1-7; phase 2, days 8-21) with a completely randomized block design. Pigs were randomly divided into 4 treatment groups with 6 replicate pens per treatment and 5 pigs per pen (2 barrows and 3 gilts). Dietary treatments were corn-soybean meal-based basal diet supplemented with 0, 0.01, 0.03 or 0.05% AN-GOX (1000 unit/g). The results of this study showed that average daily gain during days 1-7 and 1-21 and the concentrations of serum glutathione peroxidase and glutathione increased linearly at graduated doses of AN-GOX increased in the diet. However, dietary supplementation of AN-GOX had no effects on the apparent nutrient digestibility, faecal microbiota and faecal gas emission. In conclusion, supplementing AN-GOX to the diet of weaning pigs ameliorated weaning stress, which manifested as the increase in serum antioxidant enzyme levels, thus improving growth performance. The suitable dosage of AN-GOX used in the diet of weaning pigs was 0.05%.

A Luminol-Based Self-Illuminating Nanocage as a Reactive Oxygen Species Amplifier to Enhance Deep Tumor Penetration and Synergistic Therapy.

The dense extracellular matrix (ECM) in tumor tissues resists drug diffusion into tumors and leads to a poor prognosis. To address this problem, glucose oxidase (GOx)-modified ferritin loaded with luminol-curcumin was fabricated. Once delivered to the tumor, this luminol-based self-illuminating nanocage could actively convert glucose to reactive oxygen species (ROS) to achieve starvation therapy. Then, excessive ROS were transmitted to luminol, thereby emitting 425 nm blue-violet light. Momentarily, light was further absorbed by curcumin and ROS production was amplified. Abundant ROS helps break down the ECM network to penetrate deep into tumors. In addition, ROS produced after cell internalization can induce apoptosis of tumor cells by decreasing the mitochondrial membrane potential and can promote ferroptosis by consuming reduced glutathione. Effective penetration and multiple pathways inducing tumor cell death contributed to the efficient antitumor effect (tumor inhibition rate of GOx-modified ferritin loaded with luminol-curcumin: 71.73%). This study developed a glucose-driven self-illuminating nanocage for active tumor penetration via ROS-mediated destruction of the ECM and provided the synergetic mechanism of apoptosis and ferroptosis.

Dietary glucose oxidase and/or catalase supplementation alleviates intestinal oxidative stress induced by diquat in weaned piglets.

This study investigated the effects of dietary exogenous glucose oxidase (GOD) and/or catalase (CAT) on the intestinal antioxidant capacity and barrier function in piglets under oxidative stress. Sixty pigs assigned randomly to five treatment groups-CON: basal diet; DIQ: basal diet; GOD: basal diet + 40-U GOD/kg diet; CAT: basal diet + 50-U CAT/kg diet; and GC: basal diet + 40-U GOD/kg diet + 50-U CAT/kg diet-were analyzed. On Day 14, the CON group was injected with saline, and the others were treated with diquat. The results showed that in diquat-treated piglets, supplementation of dietary GOD and CAT elevated the superoxide dismutase and CAT activities and attenuated the malondialdehyde level in plasma and intestinal mucosa, enhanced the duodenal villus height and villus height/crypt depth ratio, upregulated ZO-1 mRNA level, and attenuated the apoptosis of the epithelial cells and caspase-3 mRNA level in the intestine. Additionally, the supplementation upregulated mRNA expression of the intestinal NF-E2-related factor 2-regulated genes in diquat-treated piglets. However, GOD combined with CAT could not alleviate oxidative damage better than supplementation of CAT or GOD alone under oxidative stress. Overall, the study provides a potential alternative that could relieve the weaning stress in piglets and help formulate antibiotic-free diets.

Effects of Dietary Glucose Oxidase Supplementation on the Performance, Apparent Ileal Amino Acids Digestibility, and Ileal Microbiota of Broiler Chickens.

This study aimed to investigate the effects of glucose oxidase (GOD) supplementation on growth performance, apparent ileal digestibility (AID) of nutrients, intestinal morphology, and short-chain fatty acids (SCFAs) and microbiota in the ileum of broilers. Six hundred 1-day-old male broilers were randomly allotted to four groups of 10 replicates each with 15 birds per replicate cage. The four treatments included the basal diet without antibiotics (Control) and the basal diet supplemented with 250, 500, or 1000 U GOD/kg diet (E250, E500 or E1000). The samples of different intestinal segments, ileal mucosa, and ileal digesta were collected on d 42. Dietary GOD supplementation did not affect daily bodyweight gain (DBWG) and the ratio of feed consumption and bodyweight gain (FCR) during d 1-21 (p > 0.05); however, the E250 treatment increased DBWG (p = 0.03) during d 22-42 as compared to control. Dietary GOD supplementation increased the AIDs of arginine, isoleucine, lysine, methionine, threonine, cysteine, serine, and tyrosine (p < 0.05), while no significant difference was observed among the GOD added groups. The E250 treatment increased the villus height of the jejunum and ileum. The concentrations of secreted immunoglobulin A (sIgA) in ileal mucosa and the contents of acetic acid and butyric acid in ileal digesta were higher in the E250 group than in the control (p < 0.05), whereas no significant differences among E500, E1000, and control groups. The E250 treatment increased the richness of ileal microbiota, but E500 and E100 treatment did not significantly affect it. Dietary E250 treatment increased the relative abundance of Firmicutes phylum and Lactobacillus genus, while it decreased the relative abundance of genus Escherichina-Shigella (p < 0.05). Phylum Fusobacteria only colonized in the ileal digesta of E500 treated broilers and E500 and E1000 did not affect the relative abundance of Firmicutes phylum and Lactobacillus and Escherichina-Shigella genera as compared to control. These results suggested that dietary supplementation of 250 U GOD/kg diet improves the growth performance of broilers during d 22-42, which might be associated with the alteration of the intestinal morphology, SCFAs composition, and ileal microbiota composition.

Cyclic reactions-mediated self-supply of H2O2 and O2 for cooperative chemodynamic/starvation cancer therapy.

Hydroxyl radical (·OH)-mediated chemodynamic therapy (CDT) and glucose oxidase (GOx)-based starvation therapy (ST) are two emerging antitumor strategies, limited by acid/H2O2 deficiency and tumor hypoxia, respectively. Herein, we developed a liposomal nanoplatform co-delivering Fe(OH)3-doped CaO2 nanocomposites and GOx molecules for synergistic CDT/ST with a complementary effect. Based on Fenton reactions initiated by iron ions, CaO2-supplied H2O2 could not only generate ·OH for H2O2-sufficient CDT, but also produce O2 to promote the catalytic efficiency of GOx under hypoxia. In return, the enhanced ST generated gluconic acid and H2O2, further amplifying CDT. Through in vitro and in vivo experiments, we demonstrated that such a mutually reinforced modality based on the cyclic Fenton/starvation reactions provided a novel and potent anticancer mechanism for the effective treatment of hypoxic cancers.