Reactive Oxygen Species Research Articles

TaFAR9 and TaFAR10 synergistically regulate fertility conversion of photo-thermo-sensitive genic male sterility lines in wheat by modulating ROS homeostasis

Photo-thermo-sensitive genic male sterility (PTGMS), which exhibits varying fertility levels under different environmental conditions, is a crucial method for heterosis utilization in wheat. However, the mechanisms underlying fertility conversion remain unclear. In the study, three BS type PTGMS lines were analyzed to study fertility conversion characteristics. The results indicated that the fertility conversion occurred during meiosis and was accompanied by an increase in reactive oxygen species (ROS) under a sterile environment. TaFAR9 encoding a novel fatty acyl CoA reductase was identified using transcriptome sequencing. Expression analysis suggested that TaFAR9 was localized in the endoplasmic reticulum (ER), with high expression levels in anthers. Furthermore, the down-regulation of TaFAR9 expression displayed characteristics of male sterility, accompanied by the accumulation of ROS. Cytological analysis revealed abnormal development in the anther and pollen walls of TaFAR9-silenced lines. Additionally, TaFAR9 and TaFAR10 were confirmed to physically interact using molecular docking simulation, yeast two-hybrid, luciferase complementation, and bimolecular fluorescence complementation assays. The reduced expression of TaFAR10 also exhibited male sterility and ROS burst. Moreover, the co-silencing of TaFAR9 and TaFAR10 produced sterility phenotypes that were similar to those observed when silencing TaFAR9 or TaFAR10 individually. Transcriptome analysis suggested that the ROS burst in BSMV: TaFAR9/10 anthers can result in cellular metabolic disorders. These findings indicate that TaFAR9 and TaFAR10 may form heterodimers that synergistically regulate fertility conversion in PTGMS lines by modulating ROS metabolism. And this study offers a fresh insight into the regulatory processes involved in fertility conversion in PTGMS lines.

Injectable Multifunctional Hyaluronan based Hydrogel Suppressing the Excessive Glucose and Reactive Oxygen Species in Diabetic Wound Treatment

In diabetic wounds, the overlapping presence of excessive glucose and reactive oxygen species (ROS) forming a vicious cycle that severely impedes the wound healing process. Despite advancements in wound care, current treatments often limit in addressing these two critical factors simultaneously. To address these challenges, this study introduces a multifunctional hydrogel system capable of dual regulation of excessive glucose and ROS levels in a hyperglycemic environment, while also provide a platform with favorable properties that support wound healing. First, by modifying hyaluronic acid (HA) chains with vinyl sulfone and thiol functional groups, the resulting hydrogel exhibited tunable gelation time, elastic modulus, and degradation rates, making it adaptable for diabetic wound management. Notably, this hydrogel allows for precise glucose and ROS regulation by encapsulating glucose oxidase (GOx), horseradish peroxidase (HRP), and tannic acid (TA) within the HA hydrogel matrix. It was verified that the hydrogels could reduce the glucose levels to desired concentration by varying the encapsulated GOx content. Simultaneously, the combined ROS-scavenging effect of HRP and TA effectively addressed the excessive ROS problem. Specifically, H2O2 generated from the GOx-glucose reaction was consumed in the HRP-mediated polymerization of TA, and free radicals (OH•, DPPH) were scavenged up to 70% by TA. Due to the glucose and ROS regulation properties, this hydrogel system was able to promote the proliferation and migration of human dermal fibroblast in a hyperglycemic environment. Overall, this study offers a simple and effective approach to regulate the excessive levels of glucose and ROS in a hyperglycemic condition, which has potential in creating a multifunctional platform for diabetic wound treatment.

Assessing the discrepant role of anions in the transformation of reactive oxygen species in H2O2 and PDS system: A comparative kinetic analysis

Clarifying reactive oxygen species (ROS) variation in the presence of co-existing anions is significant for understanding the catalytic effect of magnetite (Fe3O4)-induced advanced oxidation processes (AOPs) in natural environment, yet this remains controversial. Herein, we compare the specific impacts of NO3-, SO42-, and Cl- on ROS (•OH, SO4•-, O2•-, and 1O2) exposure concentration in H2O2 and peroxydisulfate (PDS) systems, as well as how these variations affect the catalytic efficiency by developing kinetic model. In both two systems, NO3- demonstrates no discernible effect on ROS, whereas SO42- inhibits the exposure of all ROS and thus micropollutants degradation. Through theoretical calculation, it is proposed that SO42- primarily exerts its influence through affecting the electronic structure over catalyst surface. Regarding Cl-, it affects ROS exposure mainly by reacting with ROS. It shows inhibitory effect on 1O2 in both systems, but its suppressive impact on •OH is markedly more pronounced in H2O2 system compared to PDS system, which may be related to its rapid reactivity with SO4•-. Besides, the chlorine radicals (mainly ClO•) generated through the reaction of Cl- may exert a selective influence on micropollutants degradation. This study can help to re-understand the influence behavior of co-existing anions during AOPs.

Morphological, physiological, and biochemical responses of rice (Oryza sativa L.) varieties to drought stress via regulating respiration and ROS metabolism during germination

Germination marks a pivotal and sensitive phase in the life cycle of crops, with drought stress, precipitated by water scarcity, posing a significant impediment to the germination process in rice. Despite this, the regulation mechanism of respiratory and reactive oxygen species (ROS) metabolism during rice germination under drought stress remains to be fully elucidated. This manuscript presents an integrative analysis encompassing morphological, physiological, biochemical, and molecular attributes of germinated seeds from a cultivated drought-sensitive rice variety (JN10) and a drought-resistant rice variety (NG36). Our findings revealed that drought stress adversely affected the germination of both rice varieties, with NG36 exhibiting a more rapid germination rate compared to JN10 under such stress conditions. This differential response was attributed to the heightened activity of key enzymes, elevated levels of metabolic intermediates, and upregulated expression of genes encoding enzymes involved in ROS and respiratory metabolic pathways in NG36. To further dissect the interplay between these metabolic pathways, we selected specific enzyme activities for detailed examination. Notably, a robust positive linear correlation was established among phosphofructokinase (PFK), α-ketoglutarate dehydrogenase (KGDH), citrate synthase (CS), and isocitrate dehydrogenase (ICDH) in NG36. This correlation underscores the pivotal role of glycolytic pathways, particularly the tricarboxylic acid (TCA) cycle, in conferring drought resistance to NG36 during the germination phase under drought stress. To encapsulate our findings, the results of this investigation suggest that the rice cultivar NG36 manifests a heightened degree of drought tolerance relative to JN10. This is primarily achieved through the adept modulation of its respiratory metabolic pathways and the stringent preservation of ROS homeostasis during the germination phase under conditions of water deficit. These revelations provide unprecedented insights into the intricate regulatory mechanisms that subserve rice's drought resistance, potentially paving the way for the development of novel strategies in the breeding of rice cultivars with improved drought resilience.

Bandgap-level engineered photodynamic antibacterial film with boosting ROS production for long-term fruit preservation

The growing demands for fruit preservation have inspired researchers to concentrate on developing advanced food packaging films with sustained and efficient antimicrobial properties. Herein, a visible light-powered photodynamic antimicrobial packaging system with enhanced reactive oxygen species (ROS) production capability (Bi/BiOI1-x-CS) was developed by demand-driven engineering of the bandgap structure of the photo-responsive filler (Bi/BiOI1-x) and the ingenious selection of chitosan matrix (CS) with bacteria capture and killing capabilities. This film displayed excellent photocatalytic killing performance against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) under the visible light, with the bactericidal efficiency up to 99.36 % and 99.54 %, respectively. The enhancement stemmed from the reasonable optimization of the following two aspects: (i) The iodine defects and lateral modification of pure bismuth jointly optimized the electronic band structure of BiOI and significantly boosted the ROS production level, and (ii) The capturing characteristic of CS on bacteria might shorten the diffusion distance between ROS and bacteria, thus further amplifying the bactericidal effect of ROS. As a result, the as-prepared Bi/BiOI0.201-x-CS film (0.20 shows the Bi/BiOI1-x amount in film solution) exhibited enhanced preservation ability, significantly extending the shelf life of kumquats from 18 to 27 days. Meanwhile, the introduction of Bi/BiOI1-x successfully promoted the mechanical properties, ultraviolet-barrier performance, and hydrophobicity of CS film. The enhancement of comprehensive performance underscores the potential application of Bi/BiOI1-x-CS film in the field of fruit preservation.

Modulation of cutaneous vasodilation by reactive oxygen species during local and whole body heating in young and older adults.

We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVCmax) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with 1) Ringer solution (control), 2) 100 µM apocynin (NADPH oxidase inhibitor), 3) 10 µM allopurinol (xanthine oxidase inhibitor), or 4) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (protocol 1) and whole body heating (protocol 2). In protocol 1, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In protocol 2, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In protocol 1, there were significant treatment site by age interactions for the 39°C (P = 0.015) and 42°C (P = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In protocol 2, there was a significant treatment site by age interaction (P < 0.001), where %CVCmax in older adults was 11.0% [7.4, 14.6] higher for apocynin (P < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (P < 0.001), and 4.8% [1.3, 8.4] higher for tempol (P = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality.NEW & NOTEWORTHY We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating.

1α,25-hydroxyvitamin D3 alleviated rotavirus infection induced ferroptosis in IPEC-J2 cells by regulating the ATF3-SLC7A11-GPX4 axis

Rotavirus (RV) mainly infects mature intestinal epithelial cells and impairs intestinal absorption function, which leads to the death of infected cells and eventually fatal diarrhea. Ferroptosis is a novel regulatory cell death pattern, which can be caused by virus infection. 1α,25-hydroxyvitamin D3 (1,25D3) has an anti-RV infection effect and can regulate ferroptosis. However, whether RV infection can induce ferroptosis, and whether 1,25D3 can inhibit RV infection by regulating ferroptosis has not yet been studied. Present study shows that RV infection or erastin treatment induces IPEC-J2 cell death, which results in mitochondrial shrinkage, decreased mitochondrial membrane potential (MMP) and glutathione (GSH) content, increased MMP, intracellular Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA) contents. Meanwhile, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1), and deferoxamine (DFO) treatment can effectively reverse the increase of intracellular Fe2+, ROS and MDA levels induced by RV infection. Moreover, RV infection increases activating transcription factor 3 (ATF3) mRNA and protein expressions, and inhibited SLC7A11 and glutathione peroxidase 4 (GPX4) expressions, which was partially alleviated by siATF3. 1,25D3 treatment significantly eliminates RV induced ferroptosis via ATF3-SLC7A11-GPX4 axis. Therefore, our results reveals that RV infection induces ferroptosis in IPEC-J2 cell and 1,25D3 alleviates RV induced ferroptosis by regulating the ATF3-SLC7A11-GPX4 axis.

Effect of natural astaxanthin on sperm quality and mitochondrial function of breeder rooster semen cryopreservation

Cryopreservation causes higher reactive oxygen species (ROS) concentrations, leading to oxidative stress and lipid peroxidation damaging sperm, and using antioxidants can improve semen quality after freeze-thaw. Natural astaxanthin (ASTA) can be inserted into cell membranes and its antioxidant properties are stronger than other antioxidants. We aimed to investigate the effects of ASTA supplementation in the Beltsville Poultry Semen Extender (BPSE) on post-thaw rooster semen quality and to explore the potential mechanism of rooster semen quality change. The qualifying semen ejaculates collected from 30 adult male Jinghong No. 1 laying hen breeder roosters (65 wk old) were pooled, divided into four aliquots, and diluted with BPSE having different levels of ASTA (0, 0.5, 1, or 2 μg/mL). Treated semen was cryopreserved and kept in liquid nitrogen. The entire experiment was replicated three times independently. Sperm viability, motility, curvilinear velocity, amplitude of lateral head displacement, straightness, plasma membrane integrity, and acrosome integrity were observed to be highest (P < 0.05) with 1 μg/mL ASTA at freeze-thawing. Higher (P < 0.05) antioxidant enzyme (CAT-like, SOD) activities and free radical (·OH, O2.-) scavenging ability, less ROS and malondialdehyde (MDA) concentrations were recorded with the addition of appropriate concentrations of ASTA compared to control. In addition, the levels of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), and lactate dehydrogenase (LDH) in the 1 μg/mL ASTA group improved compared to the control group, and decreased the amount of AIF protein level but increased the Bcl-2 protein level (P < 0:05). Collectively, these results demonstrate that adding ASTA in the BPSE promoted rooster freeze-thaw sperm quality, which may be related to reducing ROS levels, protecting the antioxidant defense system, preventing lipid peroxidation, improving mitochondrial structural and functional integrity, and inhibiting sperm apoptosis.

Dual-metal synergy unlocking ROS-free catalysis for rapid aerobic oxidation of 5-hydroxymethylfurfural at room temperature

Clean catalytic oxidation has a broad prospect in the modern chemical engineering and energy chemistry fields. However, unexpected over-oxidation and disruptive degradation are frequently induced by excessive reactive oxygen species (ROS). Herein, we reported a new ROS-free approach to effectively drive O2 to be activated into highly reactive surface peroxo species through enzyme-mimicking mechanism. Benefiting from the dual-metal synergy effect between Cu and Co active sites, ROS (H2O2 and OH•) is generated in situ while further scavenged completely into surface peroxo species, which gives rise to very high selectivity and extremely high carbon balance. For example, the CuCo/N-C catalyst affords >99.8% conversion and 94.5% selectivity to 2,5-furanedicarboxylic acid at 25 °C for 6 h in the aerobic oxidation of biomass platform 5-hydroxymethylfurfural. Moreover, it achieved exceptional performance in the oxidation of a variety of hydroxyl compounds to organic acids with high yields (89.9%–99.5%) at a mild temperature (25–40 °C). This exploration introduces an innovative clue for emulating enzyme catalysts, thereby enriching our comprehension and advancement of biologically inspired catalytic oxidations.

The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.

NADPH oxidase, as a major source of intracellular reactive oxygen species (ROS), assumes an important role in the immune response and oxidative stress response of the body. NADPH oxidase 2 (NOX2) is the first and most representative member of the NADPH oxidase family, and its effects on the development of tumor cells are gaining more and more attention. Our previous study suggested that NCF4 polymorphism in p40phox, a key subunit of NOX2, affected the outcome of diffuse large B-cell lymphoma patients treated with rituximab. It hypothesized that NOX2-mediated ROS could enhance the cytotoxic effects of some anti-tumor drugs in favor of patients with tumors. Several reviews have summarized the role of NOX2 and its congeners-mediated ROS in anti-tumor therapy, but few studies focused on the relationship between the expression of NOX2 and anti-tumor drug resistance. In this article, we systematically introduced the NOX family, represented by NOX2, and a classification of the latest inhibitors and agonists of NOX2. It will help researchers to have a more rational and objective understanding of the dual role of NOX2 in tumor drug resistance and is expected to provide new ideas for oncology treatment and overcoming drug resistance in cancer.

Degradation of 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV328) in soil by FeS activated persulfate: Kinetics, mechanism, and theoretical calculations

2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV328) is a commonly used benzotriazole ultraviolet stabilizers (BUVs) with bioaccumulative properties. Since it’s stubbornly degraded in the environment, it poses significant environmental risks in soil. However, the removal of UV328 from soil is challenging, and existing treatment methods have low efficiency. This study focuses on UV328 in soil and proposes an efficient method for its removal using persulfate (PS) activated by iron sulfide (FeS). The research demonstrates that with FeS and PS dosages of 20 and 100 mM respectively, and a soil-to-water ratio of 5:1, 12 h-removal efficiency of UV328 with an initial concentration of 12 mg/kg reaches 93.0%. Furthermore, employing electron paramagnetic resonance spectroscopy and quenching experiments, key reactive oxygen species (ROSs) are identified. SO4•-, •OH, 1O2 and •O2- contribute 31.76%, 28.77%, 26.52% and 12.95%, respectively. Four main reaction pathways of amination, hydroxylation, sulfate substitution, and bond cleavage, are identified with 14 transformation products characterized. Calculated energy profiles based on density functional theory (DFT) identify the most susceptible reaction sites for different ROSs. Five different types of agricultural soils were selected to explore the impact of soil characteristics on UV328 removal. The degradation performance of natural mackinawite demonstrates the effectiveness and accessibility of raw materials. Toxicity assessments of transformation products confirm the environmental friendliness of this system. This study proposes an efficient degradation method for UV328-contaminated soil, providing scientific insights and theoretical guidance for addressing environmental removal of BUVs from soil.

Shikonin protects skin cells against oxidative stress and cellular dysfunction induced by fine particulate matter.

Shikonin, an herbal naphthoquinone, demonstrates a broad spectrum of pharmacological properties. Owing to increasingly adverse environmental conditions, human skin is vulnerable to harmful influences from dust particles. This study explored the antioxidant capabilities of shikonin and its ability to protect human keratinocytes from oxidative stress induced by fine particulate matter (PM2.5). We found that shikonin at a concentration of 3 µM was nontoxic to human keratinocytes and effectively scavenged reactive oxygen species (ROS) while increasing the production of reduced glutathione (GSH). Furthermore, shikonin enhanced GSH level by upregulating glutamate-cysteine ligase catalytic subunit and glutathione synthetase mediated by nuclear factor-erythroid 2-related factor. Shikonin reduced ROS levels induced by PM2.5, leading to recovering PM2.5-impaired cellular biomolecules and cell viability. Shikonin restored the GSH level in PM2.5-exposed keratinocytes via enhancing the expression of GSH-synthesizing enzymes. Notably, buthionine sulphoximine, an inhibitor of GSH synthesis, diminished effect of shikonin against PM2.5-induced cell damage, confirming the role of GSH in shikonin-induced cytoprotection. Collectively, these findings indicated that shikonin could provide substantial cytoprotection against the adverse effects of PM2.5 through direct ROS scavenging and modulation of cellular antioxidant system.

ROS-Induced Gingival Fibroblast Senescence: Implications in Exacerbating Inflammatory Responses in Periodontal Disease.

Periodontal disease is the pathological outcome of the overwhelming inflammation in periodontal tissue. Cellular senescence has been associated with chronic inflammation in several diseases. However, the role of cellular senescence in the pathogenesis of periodontal disease remained unclear. This study aimed to investigate the role and the mechanism of cellular senescence in periodontal disease. Using single-cell RNA sequencing, we first found the upregulated level of cellular senescence in fibroblasts and endothelial cells from inflamed gingival tissue. Subsequently, human gingival fibroblasts isolated from healthy and inflamed gingival tissues were labeled as H-GFs and I-GFs, respectively. Compared to H-GFs, I-GFs exhibited a distinct cellular senescence phenotype, including an increased proportion of senescence-associated β-galactosidase (SA-β-gal) positive cells, enlarged cell morphology, and significant upregulation of p16INK4A expression. We further observed increased cellular reactive oxygen species (ROS) activity, mitochondrial ROS, and DNA damage of I-GFs. These phenotypes could be reversed by ROS scavenger NAC, which suggested the cause of cellular senescence in I-GFs. The migration and proliferation assay showed the decreased activity of I-GFs while the gene expression of senescence-associated secretory phenotype (SASP) factors such as IL-1β, IL-6, TGF-β, and IL-8 was all significantly increased. Finally, we found that supernatants of I-GF culture induced more neutrophil extracellular trap (NET) formation and drove macrophage polarization toward the CD86-positive M1 pro-inflammatory phenotype. Altogether, our findings implicate that, in the inflamed gingiva, human gingival fibroblasts acquire a senescent phenotype due to oxidative stress-induced DNA and mitochondrial damage, which in turn activate neutrophils and macrophages through the secretion of SASP factors.

Metallo‐supramolecular nanofibers based on type‐I photosensitizer for synergistic antibacterial therapy

AbstractPhotodynamic therapy (PDT) has shown great merits in treating microbial infections due to its absence of bacterial resistance. However, the pronounced hypoxic microenvironment in the bacterial infections limits the therapeutic efficiency of traditional type‐II PDT, which is highly dependent on oxygen. Here type‐I photosensitizer BTZn‐Py (n = 8, 20) coordinates with chemical antibacterial agent Ag+ to fabricate metallo‐supramolecular nanofibers. Under light irradiation, the formed nanofibers could not only generate type‐II reactive oxygen species (ROS), 1O2, but also produce type‐I ROS O2•− which addressed the hypoxic issues within infected tissues. Moreover, the acid‐ and photo‐active Ag+ release from the nanofibers endowed the metallo‐supramolecular nanofibers with controlled release characteristic, which showed good biocompatibility to normal tissues. Owing to controlled Ag+ release and photoinduced type‐I ROS, the in vitro and in vivo experiments confirmed the significantly synergistic antibacterial performance of the metallo‐supramolecular fibers against both Gram‐positive and Gram‐negative bacteria.

Therapeutic potential of diosgenin against methotrexate-induced testicular damage in the rat.

This study evaluated diosgenin effects on methotrexate-induced testicular injury in the rats. A single dose of methotrexate (MTX) (20mg/kg, i.p) was administered, followed by two weeks of diosgenin treatment via gavage starting one day before methotrexate injection. Testicular damage was evaluated through histological examination of seminiferous tubules, as well as analysis of serum testosterone level, oxidative stress and inflammation biomarkers, and antioxidant levels. The results of this study showed that in the MTX-exposed group, oxidative stress indices of malondialdehyde (MDA), reactive oxygen species (ROS), nitrite and indices of inflammation consisting of tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) have a significant increase compared to the control group. Additionally, reductions were observed in antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). In addition, testosterone level decreased and signs of testicular damage were observed in the MTX group. Conversely, in the group treated with diosgenin alongside MTX at a dosage of 50mg/kg, there was a significant decrease in oxidative stress markers (MDA, ROS, nitrite) and inflammatory markers (TNFα and IL-6). Moreover, there was a significant increase in the levels of antioxidant enzymes (SOD, CAT, and GSH). Diosgenin appears to have the potential to protect testicular tissue from damage caused by the toxic effects of MTX through the reduction of oxidative stress and inflammation.

Beyond glucose: The crucial role of redox signaling in β-cell metabolic adaptation

ObjectiveRedox signaling mediated by reversible oxidative cysteine thiol modifications is crucial for driving cellular adaptation to dynamic environmental changes, maintaining homeostasis, and ensuring proper function. This is particularly critical in pancreatic β-cells, which are highly metabolically active and play a specialized role in whole organism glucose homeostasis. Glucose stimulation in β-cells triggers signals leading to insulin secretion, including changes in ATP/ADP ratio and intracellular calcium levels. Additionally, lipid metabolism and reactive oxygen species (ROS) signaling are essential for β-cell function and health. MethodsWe employed IodoTMT isobaric labeling combined with tandem mass spectrometry to elucidate redox signaling pathways in pancreatic β-cells. ResultsGlucose stimulation significantly increases ROS levels in β-cells, leading to targeted reversible oxidation of proteins involved in key metabolic pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum (ER), and insulin secretion. Furthermore, the glucose-induced increase in reversible cysteine oxidation correlates with the presence of other post-translational modifications, including acetylation and phosphorylation. ConclusionsProper functioning of pancreatic β-cell metabolism relies on fine-tuned regulation, achieved through a sophisticated system of diverse post-translational modifications that modulate protein functions. Our findings demonstrate that glucose induces the production of ROS in pancreatic β-cells, leading to targeted reversible oxidative modifications of proteins. Furthermore, protein activity is modulated by acetylation and phosphorylation, highlighting the complexity of the regulatory mechanisms in β-cell function.

Melatonin protects bovine oocyte from βHB-induced oxidative stress through the Nrf2 pathway

Accumulation of ketone bodies in the blood or tissues can trigger ketosis, exerting detrimental effects on bovine oocytes maturation. Exposure to its primary component, β-hydroxybutyric acid (βHB), disrupts mitochondrial function, culminating in the excessive buildup of reactive oxygen species (ROS) and subsequent initiation of apoptosis in oocytes. These ultimately result in poor oocyte quality. Melatonin, recognized for its endogenous antioxidant properties, is capable of mitigating ROS levels and enhancing the expression of antioxidant enzymes. In this study, we explored the protective effects of melatonin on the damages induced by βHB. Melatonin was added at a concentration of 10-9 M to the culture medium on bovine oocytes. Parameters including first polar body extrusion rate, mitochondrial membrane potential, ROS, cell apoptosis were assessed. Results showed that melatonin could restore bovine oocyte maturation rate, enhance mitochondrial function, reduce cell apoptosis rate, and mitigate oxidative stress levels. Notably, Nrf2 signaling pathway inhibitor ML385 significantly attenuated the protective effects of melatonin on oxidative stress induced by βHB exposure. In summary, our study demonstrates that melatonin can protect oocytes from oxidative stress induced by βHB exposure, with indications that this protective mechanism may be mediated through the Nrf2 pathway.

“Nano knife” for efficient piezocatalytic inactivation of amoeba spores and their intracellular bacteria: Synergetic effect between physical damage and chemical oxidation

Microbial interactions between infectious agents severely interfere with the disinfection process, and current disinfection methods are unable to effectively inactivate intracellular pathogens, posing a new threat to drinking water safety. In this study, we first reported the high efficiency of piezocatalysis in inactivating amoebae and their intracellular bacteria. Results showed that the inactivation rates of the MoS2/rGO piezocatalytic system for amoebic spores and their intracellular bacteria were 4.18 and 5.02-log, respectively, within 180min. Based on scavenger studies and ESR tests, the efficient inactivation of pathogens can be attributed to the generation of reactive oxygen species (ROS), and different pathogens exhibit varying tolerances to distinct ROS. Moreover, TEM analysis revealed that the sharp edge of MoS2/rGO was conducive to the physical cutting of amoeba's cell wall and membrane, promoting the attack of ROS and ensuring a more thorough deactivation. Additionally, the intracellular ROS produced by amoebae is not only conducive to the inactivation of amoebae but also the main reason for the inactivation of bacteria in spores. This study provides a new solution for the inactivation of amoeba spores and their intracellular bacteria and emphasizes the high efficiency of the synergistic effect of physical damage and chemical oxidation.

Liquidambaric acid inhibits cholangiocarcinoma progression by disrupting the STAMBPL1/NRF2 positive feedback loop

BackgroundAbnormal antioxidant capacity in cancer cells is intimately linked to tumor aggressiveness. Modulating oxidative stress status and inhibiting ferroptosis represents a novel anticancer therapeutic strategy. STAM Binding Protein Like 1 (STAMBPL1), a deubiquitinase, is implicated in various malignancies, yet its function in inhibiting ferroptosis and therapeutic potential for cholangiocarcinoma (CCA) remains unexplored. Purpose: This study elucidates STAMBPL1's function in ferroptosis and evaluates liquidambaric acid (LDA) as its inhibitor for therapeutic applications. MethodsUsing bioinformatics, WB, IHC, the expression and prognostic value of STAMBPL1 in CCA tissue was detected. The carcinogenic capacity of STAMBPL1 and LDA were assessed through CCK-8, EdU, cloning, transwell, scratch, apoptosis, and cell cycle assays. Flow cytometry and fluorescence microscopy, as well as transmission electron microscopy (TEM), examines the effects of STAMBPL1 and LDA on intracellular reactive oxygen species (ROS) and changes in mitochondrial membrane potential. The tumorigenic ability of STAMBPL1 and LDA in vivo was evaluated through subcutaneous tumor model and lung metastasis model. The underlying mechanism of STAMBPL1 was explored using immunoprecipitation coupled with Mass spectrometry (IP/MS), Co-immunoprecipitation (Co-IP), GST pull-down, DNA pull-down, and Dual-luciferase reporter assays. Molecular docking simulations, SPR, DARTS and CETSA predict the putative binding site of LDA on STAMBPL1 protein. Rescue experiments further confirmed the above conclusions. ResultsThis study unveils the upregulation and oncogenic role of STAMBPL1 in CCA. Functionally, STAMBPL1 notably enhances CCA cell proliferation and metastasis while impeding ferroptosis. STAMBPL1 stabilizes NRF2, a pivotal regulator of antioxidant enzymes, through K63 deubiquitination. Elevated NRF2, stabilized by STAMBPL1 overexpression, triggers GPX4 activation and reactive oxygen species (ROS) elimination. Particularly, sites 251-436 of STAMBPL1 interact with sites 228-605 of NRF2, facilitating DUB activity and eliminating ubiquitin molecules attached to NRF2, thus protecting it from proteasome-mediated degradation. Moreover, NRF2, acting as a transcription factor, binds to the promoter region of STAMBPL1 and activates its transcription, thus forming STAMBPL1/NRF2 positive feedback loop and regulating redox homeostasis. Molecular docking and in vitro/in vivo experiments identified that LDA binds to and inhibits STAMBPL1, thereby disrupting the STAMBPL1/NRF2 positive feedback loop, consequently suppressing CCA progression. ConclusionThis study firstly reveals that STAMBPL1 promotes cholangiocarcinoma progression by upregulating NRF2, indicating that targeting the STAMBPL1/NRF2 axis is a novel therapeutic strategy. Additionally, our findings firstly suggest that LDA can bind to STAMBPL1, inhibiting NRF2 deubiquitination and offering significant therapeutic potential.

ALDH2 attenuates radiation-induced lung injury by inhibiting ROS and epithelial-mesenchymal transition mediated by the TGF-β1/Smad pathway

Radiation-induced lung injury is a significant complication of thoracic malignant tumor radiotherapy, yet effective treatments remain scarce. Aldehyde dehydrogenase 2 (ALDH2) possesses antioxidant and anti-inflammatory properties, but its specific role in radiation-induced lung injury is not well understood. This study aimed to investigate the impact of ALDH2 on radiation-induced lung injury and elucidate the underlying mechanisms. Through analysis of radiation-induced lung injury datasets, intervention with ALDH2 agonists and inhibitors in an in vivo radiation-induced lung injury model, and establishment of an in vitro radiation-induced lung injury model using A549 stable cells with varying ALDH2 expressions, we discovered that ALDH2 expression is reduced in radiation-induced lung injury. Enrichment analysis suggested that ALDH2 may mitigate radiation-induced lung injury by modulating oxidative stress and inflammation levels. Additionally, single-cell data analysis reveals that ALDH2 is primarily localized in myeloid macrophages within the lungs, with its expression also being reduced in lung cancer patients. Subsequent examination of mouse pathological sections, reactive oxygen species (ROS), and inflammatory factor levels confirmed that ALDH2 can lessen radiation-induced lung injury by suppressing ROS and inflammatory factors. Both in vivo and in vitro Western blot analysis further validated that ALDH2 can attenuate epithelial-mesenchymal transition and inhibit the TGF-β1/Smad pathway. Therefore, ALDH2 shows promise in reducing radiation-induced lung injury by inhibiting ROS and TGF-mediated epithelial-mesenchymal transition, making it a potential target for the treatment of radiation-induced lung injury.