Endogenous Glutathione Research Articles

Metal organic frameworks based intelligent nanoadjuvants for boosting tumor immunotherapy through enhanced ICD and lactic acid regulation

Immunotherapy has been considered as a potent antitumor modality while its efficacy is frequently hampered by the insufficient immunogenicity and immunosuppressive tumor microenvironment (TME) with overexpressed lactic acid (LA). Herein, an intelligent nanoadjuvant MOF@LOD-siRNA@Lips-FA (MLSLF) was developed by loading lactate oxidase (LOD) and monocarboxylate transporter 4 (MCT4)-inhibiting siRNA into Fe-MOF and further coated with folate-liposomes (FA-lip) for enhanced immunotherapy. The MLSLF could response to endogenous glutathione (GSH), resulting in the depletion of GSH and production of •OH for effective chemodynamic therapy (CDT). On one hand, the death of cancer cells would arouse immunogenic cell death (ICD) to release antigens and enhance tumor immunogenicity. Meanwhile, LOD could decompose intracellular LA to H2O2, which could further promote ICD and boost anti-tumor immune response. On the other hand, the siRNA could restrict the expression of MCT4, which would hinder the intracellular LA efflux. The combination of LOD and siRNA could reduce the LA content in TME and relieve immunosuppression TME. The in vivo results revealed that MLSLF could effectually suppress the growth of primary and distant tumors in tumor-bearing mice. Therefore, the smart MLSLF could be a synergistic anti-tumor strategy for efficient immunotherapy through the combination of enhanced ICD and LA metabolism blockade.

Surface curvature-induced oriented assembly of sushi-like Janus therapeutic nanoplatform for combined chemodynamic therapy

BackgroundChemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency.ResultsHerein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO2 nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO2 nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO2 nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO2 subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced ·OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as ~ 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform.ConclusionsIn general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.

Lactobacillus plantarum AR113 attenuates liver injury in D-galactose-induced aging mice via the inhibition of oxidative stress and endoplasmic reticulum stress

Probiotics could effectively eliminate excess reactive oxygen species (ROS) generated during aging or lipid metabolism disorders, but their mechanism is unclear. The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice. The result showed that pretreatment with L. plantarun AR113 significantly relieving H2O2 induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities. In D-galactose induced aging mice, L. plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione (GSH) synthesis and activating the Nrf2/Keap1 signaling pathway in mice, and increasing the expression of regulated phase II detoxification enzymes and antioxidant enzymes. Further analysis shown that gavage of L. plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78 (GPR78) and C/EBP homologous protein (CHOP) proteins, and promote the restoration of endoplasmic reticulum (ER) homeostasis, thereby activating cell anti-apoptotic pathways. These results were also confirmed in H2O2-treated HepG2 experiments. It indicated that L. plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress. L. plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.

Redox-active polyphenol nanoparticles deprive endogenous glutathione of electrons for ROS generation and tumor chemodynamic therapy

Chemodynamic therapy (CDT) based on generating reactive oxygen species (ROS) is promising for cancer treatment. However, the intrinsic H2O2 is deficient for CDT, and glutathione (GSH) eliminates ROS to protect tumor cells from ROS cytotoxicity. Herein, we propose a strategy to switch the electron flow direction of GSH for O2 reduction and ROS generation rather than ROS clearance by using P(DA-Fc) nanoparticles, which are polymerized from ferrocenecarboxylic acid (Fc) coupled dopamine. P(DA-Fc) NPs with phenol-quinone conversion ability mimic NOX enzyme to deprive electrons from GSH to reduce O2 for H2O2 generation; the following •OH release can be triggered by Fc. Semiquinone radicals in P(DA-Fc) are significantly enhanced after GSH treatment, further demonstrated with strong single-electron reduction ability by calculation. In vitro and in vivo experiments indicate that P(DA-Fc) can consume intrinsic GSH to produce endogenous ROS; ROS generation strongly depends on GSH/pH level and eventually causes tumor cell death. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to ROS producer, explores new roles of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve the efficiency of CDT. Statement of SignificanceP(DA-Fc) nanoparticles performing tumor microenvironment response capacity and tumor reductive power utilize ability were fabricated for CDT tumor suppression. After endocytosis by tumor cells, P(DA-Fc) deprived GSH of electrons for H2O2 and •OH release, mimicking the intrinsic ROS production conducted by NADPH, further inducing tumor cell necrosis and apoptosis. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to producer, explores new functions of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve CDT efficiency.

Redox Regulation in Age-Related Cataracts: Roles for Glutathione, Vitamin C, and the NRF2 Signaling Pathway.

Age is the biggest risk factor for cataracts, and aberrant oxidative modifications are correlated with age-related cataracts, suggesting that proper redox regulation is important for lens clarity. The lens has very high levels of antioxidants, including ascorbate and glutathione that aid in keeping the lens clear, at least in young animals and humans. We summarize current functional and genetic data supporting the hypothesis that impaired regulation of oxidative stress leads to redox dysregulation and cataract. We will focus on the essential endogenous antioxidant glutathione and the exogenous antioxidant vitamin C/ascorbate. Additionally, gene expression in response to oxidative stress is regulated in part by the transcription factor NRF2 (nuclear factor erythroid 2-related factor 2 [NFE2L2]), thus we will summarize our data regarding cataracts in Nrf2-/- mice. In this work, we discuss the function and integration of these capacities with the objective of maintaining lens clarity.

Chemodynamic therapy agent optimized mesoporous TiO2 nanoparticles for Glutathione-Enhanced and Hypoxia-Tolerant synergistic Chemo-Sonodynamic therapy

Sonodynamic therapy (SDT) can generate reactive oxygen species to kill cancer cells by activating sonosensitizers under ultrasound (US) irradiation. Nevertheless, its application is greatly limited by low quantum yield of sonosensitizers, high levels of endogenous glutathione (GSH) and tumor hypoxia. Herein, a GSH-activated sonosensitizers with synergistic therapy effect (chemodynamic therapy (CDT) and SDT) are developed by depositing Fe(III)-artemisinin infinite coordination polymers (Fe(III)-ART CPs) in pores of mesoporous TiO2 nanoparticles (NPs). The formed Fe(III)-ART-TiO2 NPs have high sono-induced electron-hole separation efficiency because the deposited Fe(III)-ART CPs can provide isolated intermediate bands to capture sono-induced electrons in TiO2 NPs. Meanwhile, Fe3+ in Fe(III)-ART-TiO2 NPs are reduced to Fe2+ by GSH with oxygen-deficient sites generated to further capture sono-induced electrons in TiO2 NPs. Based on this, the reaction efficiency between water molecules and sono-induced holes is high enough to generate numerous hydroxyl radicals (•OH) without oxygen participated for overcoming tumor hypoxia. Additionally, through consuming GSH, the generated Fe2+ can catalyze ART to produce C-centered free radicals for CDT. Owing to these characteristics, Fe(III)-ART-TiO2 NPs show significant tumor suppression ability and good biocompatibility in vivo. The strategy of using CDT agent to modify sonosensitizers offers new options to improve SDT effect without introducing harmful substances.

The role of glutathione in periplasmic redox homeostasis and oxidative protein folding in Escherichia coli

The thiol redox balance in the periplasm of E. coli depends on the DsbA/B pair for oxidative power and the DsbC/D system as its complement for isomerization of non-native disulfides. While the standard redox potentials of those systems are known, the in vivo “steady state” redox potential imposed onto protein thiol disulfide pairs in the periplasm remains unknown. Here, we used genetically encoded redox probes (roGFP2 and roGFP-iL), targeted to the periplasm, to directly probe the thiol redox homeostasis in this compartment. These probes contain two cysteine residues that are virtually completely reduced in the cytoplasm, but once exported into the periplasm, can form a disulfide bond, a process that can be monitored by fluorescence spectroscopy. Even in the absence of DsbA, roGFP2, exported to the periplasm, was almost fully oxidized, suggesting the presence of an alternative system for the introduction of disulfide bonds into exported proteins. However, the absence of DsbA shifted the steady state periplasmic thiol-redox potential from −228 mV to a more reducing −243 mV and the capacity to re-oxidize periplasmic roGFP2 after a reductive pulse was significantly decreased. Re-oxidation in a DsbA strain could be fully restored by exogenous oxidized glutathione (GSSG), while reduced GSH accelerated re-oxidation of roGFP2 in the WT. In line, a strain devoid of endogenous glutathione showed a more reducing periplasm, and was significantly worse in oxidatively folding PhoA, a native periplasmic protein and substrate of the oxidative folding machinery. PhoA oxidative folding could be enhanced by the addition of exogenous GSSG in the WT and fully restored in a ΔdsbA mutant. Taken together this suggests the presence of an auxiliary, glutathione-dependent thiol-oxidation system in the bacterial periplasm.

Engineering 2D Multienzyme-Mimicking Pyroptosis Inducers for Ultrasound-Augmented Catalytic Tumor Nanotherapy.

Overcoming apoptosis resistance is necessary to ensure an effective cancer treatment; however, it is currently very difficult to achieve. A desirable alternative for cancer treatment is the targeted activation of pyroptosis, a unique type of programmed cell death. However, the pyroptosis inducers that are efficient for cancer therapy are limited. This work reports the engineering of 2D NiCoOx nanosheets as inducers of the production of harmful reactive oxygen species (ROS), which promote intense cell pyroptosis, and that can be applied to ultrasound (US)-augmented catalytic tumor nanotherapy. The main therapeutic task is carried out by the 2D NiCoOx nanosheets, which have four multienzyme-mimicking activities: peroxidase- (POD), oxidase- (OXD), glutathione peroxidase- (GPx), and catalase- (CAT) mimicking activities. These activities induce the reversal of the hypoxic microenvironment, endogenous glutathione depletion, and a continuous ROS output. The ROS-induced pyroptosis process is carried out via the ROS-NLRP3-GSDMD pathway, and the exogenous US activation boosts the multienzyme-mimicking activities and favors the incremental ROS generation, thus inducing mitochondrial dysfunction. The anti-cancer experimental results support the dominance of NiCoOx nanosheet-induced pyroptosis. This work expands on the biomedical applications of engineering 2D materials for US-augmented catalytic breast cancer nanotherapy and deepens the understanding of the multienzyme activities of nanomaterials.

Functional Group Properties and Position Drive Differences in Xenobiotic Plant Uptake Rates, but Metabolism Shares a Similar Pathway.

Plant uptake of xenobiotic compounds is crucial for phytoremediation (including green stormwater infrastructure) and exposure potential during crop irrigation with recycled water. Experimentally determining the plant uptake for every relevant chemical is impractical; therefore, illuminating the role of specific functional groups on the uptake of trace organic contaminants is needed to enhance predictive power. We used benzimidazole derivatives to probe the impact of functional group electrostatic properties and position on plant uptake and metabolism using the hydroponic model plant Arabidopsis thaliana. The greatest plant uptake rates occurred with an electron-withdrawing functional group at the 2 position; however, uptake was still observed with an electron-donating group. An electron-donating group at the 1 position significantly slowed uptake for both benzimidazole- and benzotriazole-based molecules used in this study, indicating possible steric effects. For unsubstituted benzimidazole and benzotriazole structures, the additional heterocyclic nitrogen in benzotriazole increased plant uptake rates compared to benzimidazole. Analysis of quantitative structure-activity relationship parameters for the studied compounds implicates energy-related molecular descriptors as uptake drivers. Despite significantly varied uptake rates, compounds with different functional groups yielded shared metabolites, including an impact on endogenous glutathione production. Although the topic is complex and influenced by multiple factors in the field, this study provides insights into the impact of functional groups on plant uptake, with implications for environmental fate and consumer exposure.

Dual Active Centers Linked by a Reversible Electron Station as a Multifunctional Nanozyme to Induce Synergetically Enhanced Cascade Catalysis for Tumor-Specific Therapy.

Nanozymes have shown great promise in reactive oxygen species (ROS)-mediated tumor therapy with mitigated side effects but are normally limited by the complex tumor microenvironment (TME). Herein, to overcome the adverse effects of TME, such as tumor hypoxia and high endogenous glutathione (GSH), an aptamer-functionalized Pd@MoO3-x nano-hydrangea (A-Pd@MoO3-x NH) is constructed for high-efficiency cancer therapy. Utilizing the irregular shape characteristics of nano Pd, the A-Pd@MoO3-x NH nanozyme simultaneously exposes catalase-like Pd(111) and oxidase-like Pd(100) surface facets as dual active centers. This can catalyze cascade enzymatic reactions to overcome the negative effects of tumor hypoxia caused by the accumulation of cytotoxic superoxide (O2•-) radicals in TME without any external stimuli. In addition, the nanozyme can effectively degrade the overexpressed glutathione (GSH) through the redox reaction to avoid nontherapeutic consumption of O2•- radicals. More significantly, as a reversible electron station, MoO3-x can extract electrons from H2O2 decomposing on Pd(111) or GSH degradation and transfer them back to Pd(100) through oxygen bridges or few Mo-Pd bonds. This can synergistically enhance enzyme-like activities of dual active centers and the GSH-degrading ability to enrich O2•- radicals. In this way, the A-Pd@MoO3-x NH nanozyme can selectively and remarkably kill tumor cells while keeping the normal cell line unharmed.

Neuroprotective Efficacy of Fisetin Against VPA-Induced Autistic Neurobehavioral Alterations by Targeting Dysregulated Redox Homeostasis.

Autism is a neurodevelopmental condition, and it'sassociated pathophysiology, viz., oxidative stress and altered cellular homeostasis, has been extensively intertwined with behavioral impairments. Therefore, targeting oxidative stress and redox cellular homeostasis could be beneficial in relieving autistic-like symptoms. For this purpose, we examined a library of nutraceutical compounds that led us to a bioflavonoid fisetin. Autism-like neurobehavior was induced by subjecting the pregnant rodents to valproic acid at the time of neural tube closure (GD12.5). In this novel study, fisetin was evaluated for its neuroprotective potential at gestational (GD13 until delivery) and post-weaning developmental windows (PND 23-32) in VPA-induced rodent model of autism. Developmental VPA exposure increased intracellular ROS production, oxidative stress, altered AChE and ATPases in brain regions, and induced autistic-like behavioral impairments (social, repetitive, stereotyped, and sensorimotor). The present findings suggested that gestational and post-weaning fisetin treatment significantly improved the behavioral impairments by attenuating elevated oxidative stress, ROS, lipid peroxidation, and re-establishing redox homeostasis. Also, it effectively reinstated the reduced levels of endogenous antioxidants, glutathione, AChE, and ATPases by its antioxidant potential. Therefore, fisetin with its properties could be used as a potential therapeutic agent in overcoming the symptoms associated with autism.

Anti-oxidative and anti-inflammatory effects of different lutein isomers in Caco-2 cell model

The purpose of this work was to investigate the differences in the anti-oxidative stress and anti-inflammatory effects between all-E (trans)-lutein and its 9Z (cis)- and 13Z-isomers using the human intestinal Caco-2 cell model. I–TiO2 catalyst was used to isomerize all-E-lutein to obtain 9Z-lutein and 13Z-lutein. In anti-oxidative stress studies, all three lutein isoforms could significantly reduce H2O2-induced interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) secretion (p < 0.05) by 50% or more at 4 μM. At lower concentration (2 μM), 9Z-lutein and 13Z-lutein showed higher protection against oxidative stress than all-E-lutein by significantly reducing IL-8 secretion by 48% and 40% (p < 0.05), respectively. In addition, three lutein isomers, especially 9Z-lutein could up-regulate the activity of antioxidant enzymes including catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and the content of endogenous antioxidant glutathione (GSH) at 2 μM. In the anti-inflammatory assay, 9Z-lutein and all-E-lutein exhibited higher anti-inflammatory effects than 13Z-lutein in reducing the secretion and expression of IL-8 in TNF-α induced inflammatory Caco-2 cells. Compared with the positive control, 9Z-lutein and all-E-lutein could reduce the expression of the IL-8 gene by 49% and 52%, respectively at 4 μM. This study provided a theoretical basis for the potential health benefits of Z-luteins.

A rapid GC-FID method for determination of endogenous glutathione in wheat flour

An improved gas chromatographic method using flame ionization detection (GC-FID) for quantification of free glutathione (GSH), free glutathione disulphide (GSSG), total free glutathione (TFG) and protein bound glutathione (PSSG) in wheat flour has been developed. The process involves extraction of GSH and GSSG, wherein the extraction efficiencies of five different solvent systems, including acetonitrile, methanol, trichloroacetic acid (TCA), meta-phosphoric acid (MPA) and perchloric acid (PCA) were tested. A comparison between 1,4-dithiothreitol (DTT) and tris(2-carboxyethyl)phosphine (TCEP) was made in order to evaluate their efficacy to reduce GSSG to GSH. Results showed that TCEP reduced GSSG to GSH, and released GSH from PSSG, whereas DTT did not reduce GSSG to GSH at a sufficient level at the tested experimental conditions. The method showed a linear response for the concentration in the range of 6.25–50 nmol/mL. The limit of detection and the limit of quantification values were 2.03 and 6.08 nmol/mL, respectively. The level of GSH in 40 different wheat flours was in the range of 19.3–137 nmol GSH/g, while GSSG and PSSG levels ranged from 4.32 to 200 and 5.15–61.4 nmol GSH equivalents/g flour. Pearson's correlation coefficients showed minor positive correlations for baking volume, protein and wet gluten to GSH.

CHAC1 inactivation is effective to preserve muscle glutathione but is insufficient to protect against muscle wasting in cachexia.

Muscle wasting is one of the main characteristics of cachexia associated with cancer and other chronic diseases and is often exacerbated by antineoplastic agents. Increased oxidative stress is associated with muscle wasting, along with depletion of glutathione, the most abundant endogenous antioxidant. Therefore, boosting endogenous glutathione has been proposed as a therapeutic strategy to prevent muscle wasting. Here, we tested this hypothesis by inactivating CHAC1, an intracellular glutathione degradation enzyme. We found CHAC1 expression is increased under multiple muscle wasting conditions in animal models, including fasting, cancer cachexia, and chemotherapy. The elevation of muscle Chac1 expression is associated with reduced glutathione level. CHAC1 inhibition via CRSPR/Cas9 mediated knock-in of an enzyme inactivating mutation demonstrates a novel strategy to preserve muscle glutathione levels under wasting conditions but fails to prevent muscle wasting in mice. These results suggest that preserving intracellular glutathione level alone may not be sufficient to prevent cancer or chemotherapy induced muscle wasting.

Nanoparticles for combined photo- and chemodynamic therapy ofcancer cells involving endogenous glutathione depletion.

Background: Reactive oxygen species (ROS) are powerful weapons for various anticancer therapies. However, high glutathione (GSH) levels in cancer cells can significantly reduce the efficacy of such therapies. Methods: In this study, pH-responsive fluorescein-encapsulated zeolitic imidazolate framework-8 nanoparticleswere synthesized for ROS-mediated combination therapy. Results: Upon blue light activation, fluorescein displayed a high singlet oxygen photogeneration ability for photodynamic therapy. Concurrently, accumulated Zn2+ from degraded zeolitic imidazolate framework-8 stimulated simultaneous ROS generation and GSH depletion, thereby successfully inducing chemodynamic therapy. This triggered a cascade of photo-physical and chemical processes culminating in the localized generation of ROS, ultimately breaking the intracellular redox equilibrium. Conclusion: This nanoformulation canpotentially be used for light-activated ROS-mediated therapy for the management of superficial tumors.

Endogenous salicylic acid mediates melatonin-induced chilling-and oxidative-stress tolerance in harvested kiwifruit

Phytohormone melatonin (MT) has shown promise in alleviating chilling injury (CI) in kiwifruit; however, the performance and mechanism remain largely unknown. In this study, the effect of pretreatment of MT at concentration of 0.05 mM on CI in ‘Xuxiang’ kiwifruit during storage at 1 °C for 90 d was investigated, as well as the implication of endogenous salicylic acid (SA) in MT-induced chilling-and oxidative-stress tolerance. MT pretreatment protected kiwifruit against CI, as figured out by lower CI index, firmness loss and soluble solids accumulation and better pulp appearance than those in control fruit. MT pretreatment stimulated endogenous SA generation by activating the gene expression of phenylalanine ammonia lyase (PAL) and activity of PAL and benzoic acid-2-hydroxylase, therefore up-regulated SA-responsive pathogenesis-related gene 1 expression, and provoked kiwifruit defense response to chilling stress. Moreover, reactive oxygen species in MT-pretreated fruit were neutralized by evaluating endogenous MT, ascorbic acid and glutathione contents and superoxide dismutase, catalase and ascorbate peroxidase activity, thus reducing membrane damage. However, such positive regulations of MT on kiwifruit were counteracted to varying extent by pretreatment of the combination of paclobutrazol PAC, a SA biosynthesis inhibitor, with MT. These findings indicated a mediating role of endogenous SA in chilling-and oxidative-stress tolerance in kiwifruit induced by MT pretreatment that could be operative by evoking defense response to chilling stress and enhancing antioxidative protection.

Spatiotemporally confined assembly of radiosensitizers for synergistic radio-chemodynamic therapy on deep tumor of rabbit

The controllable assembly of nanoparticles significantly improves their biological effects in vivo. However, it is difficult to realize the assembly regulation of nanomaterials under complex physiological conditions. Herein, endogenous glutathione (GSH)-triggered vesicles with spatiotemporally confined aggregation of gold nanogapped nanoparticles (AuNNPs) within vesicles were developed. These vesicles had excellent photoacoustic (PA) imaging capability in the near-infrared second window (NIR-II) for precise localization of deep tumors, measuring tumor volume, and making deep tumors more sensitive to radiotherapy and chemodynamic therapy (CDT). The vesicles were prepared via self-assembly of MnO2-coated AuNNPs that were functionalized by phosphate-polystyrene and bovine serum albumin (AuNNP@MnO2 Ve@BSA). The MnO2 shell was etched when AuNNP@MnO2 Ve@BSA vesicle was exposed to GSH, the gap between intra-vesicular AuNNP@MnO2 NPs was reduced. This significantly enhanced the plasmonic coupling effect between AuNNP@MnO2 NPs, giving it excellent NIR-II PA imaging capability, and thus can be used to delineate the boundary and volume of deep-seated tumors. Meanwhile, the Mn2+-mediated CDT released after the etching of the MnO2 shell interacted with GSH-responsive AuNNP@MnO2 Ve@BSA and significantly inhibited tumor growth due to enhanced radiosensitization effect. This unique strategy provides new perspectives and methods for designing and applying biomedical nanomaterials.

Construction of an Endogenously Activated Signal Amplification Assay for In Situ Imaging of MicroRNA and Guided Precise Photodynamic Therapy for Cancer Cells.

The construction of a sensitive strategy for in situ visualizing and dynamic tracing intracellular microRNA is of great importance. Via the toehold-mediated strand displacement process, the catalytic hairpin assembly (CHA) could offer several hundreds-fold signal amplifications. However, the CHA may produce certain background interferences since microRNA may exist in normal cells. In this work, we constructed an endogenously and sequentially activated signal amplification strategy to provide the amplified dual-color fluorescence imaging of microRNA in living cancer cells, which was comprised of two successive reaction processes: the activation of the preprotective catalytic probe by the endogenous glutathione (GSH) and the subsequent catalytic hairpin assembly on the surface of the upconversion nanoprobe triggered by the specific microRNA. Since the concentration of GSH in cancer cells was much higher than that in normal cells and the extracellular environment, the activation of the designed nanoprobe could be controlled at the desirable site. With the merits of the endogenous initiation and selective activation, the designed nanoprobe could achieve the bioimaging of microRNA in living cancer cells with high precision and reliability. Furthermore, via the introduction of a photosensitizer molecule into the DNA strand, the designed nanoplatform could achieve the precise photodynamic therapy (PDT) for cancer cells and malignant tumors under the irradiation of the NIR laser. This work provided a new avenue to achieve the accurate imaging of intracellular microRNA and guided precise PDT, which would offer powerful hints to the early diagnosis and therapy of malignant tumors.

Glutathione for Food and Health Applications with Emphasis on Extraction, Identification, and Quantification Methods: A Review.

Glutathione is a naturally occurring compound that plays a crucial role in the cellular response to oxidative stress through its ability to quench free radicals, thus mitigating the risk of potential damage, including cell death. While glutathione is endogenously present in different plants and animal cells, their concentration varies considerably. The alteration in glutathione homeostasis can be used as a potential marker for human diseases. In the case of the depletion of endogenous glutathione, exogenous sources can be used to replenish the pool. To this end, both natural and synthetic glutathione can be used. However, the health benefit of glutathione from natural sources derived from fruits and vegetables is still debated. There is increasingly growing evidence of the potential health benefits of glutathione in different diseases; however, the determination and in situ quantification of endogenously produced glutathione remains a major challenge. For this reason, it has been difficult to understand the bioprocessing of exogenously delivered glutathione in vivo. The development of an in situ technique will also aid in the routine monitoring of glutathione as a biomarker for different oxidative stress-mediated diseases. Furthermore, an understanding of the in vivo bioprocessing of exogenously delivered glutathione will also aid the food industry both towards improving the longevity and profile of food products and the development of glutathione delivery products for long-term societal health benefits. In this review, we surveyed the natural plant-derived sources of glutathione, the identification and quantification of extracted glutathione from these sources, and the role of glutathione in the food industry and its effect on human health.

Role of selenium in type 2 diabetes, insulin resistance and insulin secretion.

Selenium is a trace mineral essential for life that acts physiologically through selenoproteins. Among other actions, the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood, selenoprotein P, seem to play an important role in type 2 diabetes mellitus and insulin resistance by weakening the insulin signaling cascade through different mechanisms. Recent findings also suggest that selenoproteins also affect insulin biosynthesis and insulin secretion. This review discussed the role of selenium in type 2 diabetes and the complex interplay between selenoproteins and insulin pathways.