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Talanta Jun 2024Although nanozyme engineering has made tremendous progress, there is a huge gap between them and natural enzymes due to the enormous challenge of precisely adjusting the...
Although nanozyme engineering has made tremendous progress, there is a huge gap between them and natural enzymes due to the enormous challenge of precisely adjusting the geometric and electronic structure of active sites. Considering that intentionally adjusting the metal-carrier interactions may bring the promising catalytic activity, in this work, a novel Mo atom nanocluster is successfully synthesized using nitrogen-doped Mxene (Mo/N-MXene) nanozymes as carriers. The constructed Mo/N-MXene displays excellent peroxidase-like catalytic activity and kinetics, outweighing its N-MXene and Mo nanoparticles (NPs)-MXene references and natural horse radish peroxidase. This work not only reports a successful example of Mo/N-MXene nanozyme as a guide for achieving peroxidase-mimic performance of nanozymes for colorimetric glutathione sensing at 0.29 μM, but also expands the application prospects of two-dimensional MXene nanosheets by reasonably introducing metal atomic clusters and nonmetal atom doping and exploring related nanozyme properties.
PubMed: 38943767
DOI: 10.1016/j.talanta.2024.126485 -
ACS Biomaterials Science & Engineering Jun 2024Metal peroxide nanomaterials as efficient hydrogen peroxide (HO) self-supplying agents have attracted the attention of researchers for antitumor treatment. However,...
Hyaluronic Acid-Modified Spherical MgO/Pd Nanocomposites Exhibit Superior Antitumor Effect through Tumor Microenvironment-Responsive Ferroptosis Induction and Photothermal Therapy.
Metal peroxide nanomaterials as efficient hydrogen peroxide (HO) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide HO is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO/Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO/Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of HO was released. Simultaneously, Pd NPs catalyze self-supplied HO to generate abundant hydroxyl radicals (OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO/Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.
PubMed: 38943566
DOI: 10.1021/acsbiomaterials.4c00555 -
Advanced Materials (Deerfield Beach,... Jun 2024The disorder of the macrophage phenotype and the hostile by-product of lactate evoked by pathogenic infection in hypoxic deep wound inevitably lead to the stagnant skin...
The disorder of the macrophage phenotype and the hostile by-product of lactate evoked by pathogenic infection in hypoxic deep wound inevitably lead to the stagnant skin regeneration. In this study, we developed HS-evolving alternately catalytic bio-heterojunction enzyme (AC-BioHJzyme) consisting of CuFeS and lactate oxidase (CuFeS@LOD). AC-BioHJzyme exhibits circular enzyme-mimetic antibacterial (EMA) activity and macrophage re-rousing capability, which can be activated by near-infrared-II (NIR-II) light. In this system, LOD exhausts lactate derived from bacterial anaerobic respiration and generated hydrogen peroxide (HO), which provides an abundant stock for the peroxidase-mimetic activity to convert the produced HO into germicidal •OH. The GPx-mimetic activity endows AC-BioHJzyme with a glutathione consumption property to block the antioxidant systems in bacterial metabolism, while the O provided by the CAT-mimetic activity can generate O under the NIR-II irradiation. Synchronously, the HS gas liberated from CuFeS@LOD under the infectious micromilieu allows the reduction of Fe(III)/Cu(II) to Fe(II)/Cu(І), resulting in sustained circular EMA activity. In vitro and in vivo assays indicate that the CuFeS@LOD AC-BioHJzyme significantly facilitates the infectious cutaneous regeneration by killing bacteria, facilitating epithelialization/collagen deposition, promoting angiogenesis and reprogramming macrophages. This study provides a countermeasure for deep infectious wound healing via circular enzyme-mimetic antibiosis and macrophage re-rousing. This article is protected by copyright. All rights reserved.
PubMed: 38943427
DOI: 10.1002/adma.202405659 -
Tree Physiology Jun 2024Stress tolerance in apple (Malus domestica) can be improved by grafting to a stress-tolerant rootstock, such as 'SH6' (Malus honanensis × M. domestica 'Ralls Genet')....
The transcription factor MhZAT10 enhances antioxidant capacity by directly activating the antioxidant genes MhMSD1, MhAPX3a, and MhCAT1 in apple rootstock SH6 (Malus honanensis × M. domestica).
Stress tolerance in apple (Malus domestica) can be improved by grafting to a stress-tolerant rootstock, such as 'SH6' (Malus honanensis × M. domestica 'Ralls Genet'). However, the mechanisms of stress tolerance in this rootstock are unclear. In Arabidopsis (Arabidopsis thaliana), the transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) is a key component of plant tolerance to multiple abiotic stresses and positively regulates antioxidant enzymes. However, how reactive oxygen species (ROS) are eliminated upon activation of ZAT10 in response to abiotic stress remains elusive. Here, we report that MhZAT10 in the rootstock SH6 directly activates the transcription of three genes encoding the antioxidant enzymes MANGANESE SUPEROXIDE DISMUTASE 1 (MhMSD1), ASCORBATE PEROXIDASE 3A (MhAPX3a), and CATALASE 1 (MhCAT1) by binding to their promoters. Heterologous expression in Arabidopsis protoplasts showed that MhMSD1, MhAPX3a, and MhCAT1 localize in multiple subcellular compartments. Overexpressing MhMSD1, MhAPX3a, or MhCAT1 in SH6 fruit calli resulted in higher superoxide dismutase, ascorbate peroxidase, and catalase enzyme activities in their respective overexpressing calli than in those overexpressing MhZAT10. Notably, the calli overexpressing MhZAT10 exhibited better growth and lower ROS levels under simulated osmotic stress. Apple SH6 plants overexpressing MhZAT10 in their roots via Agrobacterium rhizogenes-mediated transformation also showed enhanced tolerance to osmotic stress, with higher leaf photosynthetic capacity, relative water content in roots, and antioxidant enzyme activity, as well as less ROS accumulation. Overall, our study demonstrates that the transcription factor MhZAT10 synergistically regulates the transcription of multiple antioxidant-related genes and elevates ROS detoxification.
PubMed: 38943359
DOI: 10.1093/treephys/tpae077 -
Journal of Orthopaedic Surgery and... Jun 2024Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a...
Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.
BACKGROUND
Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study.
METHODS
Herein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats.
RESULTS
We discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence.
CONCLUSION
In conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.
Topics: Animals; Ferroptosis; Exosomes; NF-E2-Related Factor 2; Cellular Senescence; Rats; Signal Transduction; Phospholipid Hydroperoxide Glutathione Peroxidase; Regeneration; AMP-Activated Protein Kinases; Stem Cells; Tendons; Male; Blood Platelets; Rats, Sprague-Dawley; Rotator Cuff Injuries; Disease Models, Animal
PubMed: 38943181
DOI: 10.1186/s13018-024-04869-8 -
Scientific Reports Jun 2024Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae...
Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae are responsible for the unequal distribution of worms in natural host populations and thus investigated a susceptible versus a resistant mouse strain. In mice, the roundworm larvae develop until the lung stage and thus early anti-Ascaris immune responses against the migrating larvae in the liver and lung can be deciphered. Our data show that susceptible C57BL/6 mice respond to Ascaris larval migration significantly stronger compared to resistant CBA mice and the anti-parasite reactivity is associated with pathology. Increased eosinophil recruitment was detected in the liver and lungs, but also in the spleen and peritoneal cavity of susceptible mice on day 8 post infection compared to resistant mice. In serum, eosinophil peroxidase levels were significantly higher only in the susceptible mice, indicating functional activity of the recruited eosinophils. This effect was associated with an increased IL-5/IL-13 production by innate lymphoid cells and CD4 T cells and a pronounced type 2 macrophage polarization in the lungs of susceptible mice. Furthermore, a comparison of wildtype BALB/c and eosinophil-deficient dblGATA-1 BALB/c mice showed that eosinophils were not essential for the early control of migrating Ascaris larvae. In conclusion, in primary infection, a strong local and systemic type 2 immune response during hepato-tracheal helminth larval migration is associated with pathology rather than protection.
Topics: Animals; Ascariasis; Larva; Mice; Th2 Cells; Mice, Inbred BALB C; Lung; Ascaris; Eosinophils; Mice, Inbred C57BL; Mice, Inbred CBA; Liver; Female
PubMed: 38942904
DOI: 10.1038/s41598-024-65281-0 -
Scientific Reports Jun 2024Preterm born (PTB) infants are at risk for injuries related to oxidative stress. We investigated the association between antioxidant and neurodevelopmental gene...
Preterm born (PTB) infants are at risk for injuries related to oxidative stress. We investigated the association between antioxidant and neurodevelopmental gene polymorphisms and oxidative stress parameters in PTB male young adults and their term-born counterparts at rest and during exercise. Healthy young PTB (N = 22) and full-term (N = 15) males underwent graded exercise tests in normobaric normoxic (FO = 0.21) and hypoxic (FO = 0.13) conditions. CAT rs1001179 was associated with decrease in nitrites in the whole group and in PTB individuals (P = 0.017 and P = 0.043, respectively). GPX1 rs1050450 was associated with decrease in ferric reducing antioxidant power in the whole group and in full-term individuals (P = 0.017 and P = 0.021, respectively). HIF1A rs11549465 was associated with decrease in nitrotyrosine and increase in malondialdehyde (P = 0.022 and P = 0.018, respectively). NOTCH4 rs367398 was associated with increase in advanced oxidation protein products and nitrites (P = 0.002 and P = 0.004, respectively) in hypoxia. In normoxia, NOTCH4 rs367398 was associated with increase in malondialdehyde in the whole group (P = 0.043). BDNF rs6265 was associated with decreased nitrites/nitrates in the whole group and in PTB individuals (P = 0.009 and P = 0.043, respectively). Polymorphisms in investigated genes and PTB might influence oxidative stress response after exercise in normoxic or hypoxic conditions far beyond the neonatal period in young male adults.
Topics: Humans; Oxidative Stress; Male; Hypoxia; Antioxidants; Polymorphism, Single Nucleotide; Young Adult; Infant, Newborn; Glutathione Peroxidase GPX1; Hypoxia-Inducible Factor 1, alpha Subunit; Catalase; Adult; Glutathione Peroxidase; Infant, Premature; Nitrites; Malondialdehyde; Tyrosine; Premature Birth
PubMed: 38942829
DOI: 10.1038/s41598-024-65647-4 -
Methods in Enzymology 2024Vanadium-dependent haloperoxidases (VHPOs) are a unique family of enzymes that utilize vanadate, an aqueous halide ion, and hydrogen peroxide to produce an electrophilic...
Vanadium-dependent haloperoxidases (VHPOs) are a unique family of enzymes that utilize vanadate, an aqueous halide ion, and hydrogen peroxide to produce an electrophilic halogen species that can be incorporated into electron rich organic substrates. This halogen species can react with terpene substrates and trigger halonium-induced cyclization in a manner reminiscent of class II terpene synthases. While not all VHPOs act in this capacity, several notable examples from algal and actinobacterial species have been characterized to catalyze regio- and enantioselective reactions on terpene and meroterpenoid substrates, resulting in complex halogenated cyclic terpenes through the action of single enzyme. In this article, we describe the expression, purification, and chemical assays of NapH4, a difficult to express characterized VHPO that catalyzes the chloronium-induced cyclization of its meroterpenoid substrate.
Topics: Alkyl and Aryl Transferases; Terpenes; Cyclization; Vanadium; Substrate Specificity; Peroxidases; Enzyme Assays
PubMed: 38942514
DOI: 10.1016/bs.mie.2024.03.024 -
Plant Science : An International... Jun 2024Receptor-like kinase (ERECTA, ER) is essential for mediating growth, development, and stress response signaling pathway in plants. In this study, we investigated the...
Receptor-like kinase (ERECTA, ER) is essential for mediating growth, development, and stress response signaling pathway in plants. In this study, we investigated the effect of VvER on anthocyanin synthesis as a regulatory factor in transgenic grape callus in response to chilling stress. Results showed that overexpression of VvER reduced the expression of transcription factors VvMYBA1, VvMYB5b, VvMYC2, and VvWDR1, as well as the structural genes VvCHS, VvCHI, VvDFR, VvLDOX, and VvUFGT, and inhibited the anthocyanins synthesis of grape callus at 25℃. VvER reduced proline content and antioxidant enzymes activities of superoxide dismutase (SOD) and peroxidase (POD), and inhibited the expression of anthocyanin synthesis genes to reduce the cold resistance of grape callus. In transgenic Arabidopsis, overexpression of VvER promoted the elongation of Arabidopsis rosettes and sprigs. Under strong light treatment, VvER inhibited the accumulation of anthocyanins in Arabidopsis; Transient expression in strawberry fruit showed that VvER inhibited the synthesis of anthocyanin in strawberry fruit by inhibiting the expression of FaCHI, FaCHS, FaDFR and FaUFGT under low temperature treatment at 10°C, but not under the normal temperature of 25℃. Using Yeast two-hybrid, we found that VvER interacted with transcription factor proteins including VvMYBA1, VvMYB5b and VvWDR1. Furthermore, VvER led to the repression of VvUFGT promoter activity and decreased the anthocyanin biosynthesis genes expression by downregulation MBW complex activity. Totally, VvER could inhibit anthocyanin biosynthesis and involve in the grape plant susceptible to cold stress for grape cultivation in northern China.
PubMed: 38942388
DOI: 10.1016/j.plantsci.2024.112172 -
Archives of Biochemistry and Biophysics Jun 2024Arsenic, an environmental pollutant and poisonous metalloid, has adverse effects on different body organs, including the kidneys. Betaine is a natural nutrient that has...
Arsenic, an environmental pollutant and poisonous metalloid, has adverse effects on different body organs, including the kidneys. Betaine is a natural nutrient that has many beneficial health effects. This research was conducted to examine the impact of betaine on nephrotoxicity caused by inorganic arsenic (NaAsO) in mice. Mice were separated into following groups: control, NaAsO (50 ppm), NaAsO (50 ppm) + betaine (500 mg/kg), and betaine (500 mg/kg). Mice were received NaAsO via drinking water for 8 consecutive weeks and betaine was given to the animals via gavage once daily in the 7th and 8th weeks of the study. Upon completion of the study, the mice were euthanized and samples of serum and kidney were obtained for further evaluations. Administration of NaAsO increased the levels of blood urea nitrogen and creatinine in the serum. It enhanced the amounts of renal malondialdehyde and decreased the total thiol levels, as well as the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). Furthermore, it enhanced the levels of renal inflammatory indicators (tumor necrosis factor-alpha and nitric oxide). Western blot results exhibited an increase in the protein expression of nuclear factor kappa B (NF-κB), and phosphorylated NF-κB in NaAsO-treated mice. Histopathological results also confirmed kidney damage caused by NaAsO. However, treatment with betaine improved NaAsO-related kidney injuries in mice. The results of this work indicated that betaine can attenuate kidney damage caused by NaAsO by inhibiting oxidative stress and inflammation.
PubMed: 38942108
DOI: 10.1016/j.abb.2024.110076