Reactive Oxygen Species Activity Research Articles

Obese Adipocytes Have Altered Redox Homeostasis with Metabolic Consequences.

White and brown adipose tissues are organized to form a real organ, the adipose organ, in mice and humans. White adipocytes of obese animals and humans are hypertrophic. This condition is accompanied by a series of organelle alterations and stress of the endoplasmic reticulum. This stress is mainly due to reactive oxygen species activity and accumulation, lending to NLRP3 inflammasome activation. This last causes death of adipocytes by pyroptosis and the formation of large cellular debris that must be removed by macrophages. During their chronic scavenging activity, macrophages produce several secretory products that have collateral consequences, including interference with insulin receptor activity, causing insulin resistance. The latter is accompanied by an increased noradrenergic inhibitory innervation of Langerhans islets with de-differentiation of beta cells and type 2 diabetes. The whitening of brown adipocytes could explain the different critical death size of visceral adipocytes and offer an explanation for the worse clinical consequence of visceral fat accumulation. White to brown transdifferentiation has been proven in mice and humans. Considering the energy-dispersing activity of brown adipose tissue, transdifferentiation opens new therapeutic perspectives for obesity and related disorders.

Metal Nanomaterials and Hydrolytic Enzyme-Based Formulations for Improved Antifungal Activity.

Active research of metal-containing compounds and enzymes as effective antifungal agents is currently being conducted due to the growing antifungal resistance problem. Metals are attracting special attention due to the wide variety of ligands that can be used for them, including chemically synthesized and naturally obtained variants as a result of the so-called "green synthesis". The main mechanism of the antifungal action of metals is the triggering of the generation and accumulation of reactive oxygen species (ROS). Further action of ROS on various biomolecules is nonspecific. Various hydrolytic enzymes (glucanases and proteases), in turn, exhibit antifungal properties by affecting the structural elements of fungal cells (cell walls, membranes), fungal quorum sensing molecules, fungal own protective agents (mycotoxins and antibiotics), and proteins responsible for the adhesion and formation of stable, highly concentrated populations in the form of biofilms. A wide substrate range of enzymes allows the use of various mechanisms of their antifungal actions. In this review, we discuss the prospects of combining two different types of antifungal agents (metals and enzymes) against mycelial fungi and yeast cells. Special attention is paid to the possible influence of metals on the activity of the enzymes and the possible effects of proteins on the antifungal activity of metal-containing compounds.

β-Asarone Alleviates High-Glucose-Induced Oxidative Damage via Inhibition of ROS Generation and Inactivation of the NF-κB/NLRP3 Inflammasome Pathway in Human Retinal Pigment Epithelial Cells.

Diabetic retinopathy (DR) is the leading cause of vision loss and a major complication of diabetes. Hyperglycemia-induced accumulation of reactive oxygen species (ROS) is an important risk factor for DR. β-asarone, a major component of volatile oil extracted from Acori graminei Rhizoma, exerts antioxidant effects; however, its efficacy in DR remains unknown. In this study, we investigated whether β-asarone inhibits high-glucose (HG)-induced oxidative damage in human retinal pigment epithelial (RPE) ARPE-19 cells. We found that β-asarone significantly alleviated cytotoxicity, apoptosis, and DNA damage in HG-treated ARPE-19 cells via scavenging of ROS generation. β-Asarone also significantly attenuated the excessive accumulation of lactate dehydrogenase and mitochondrial ROS by increasing the manganese superoxide dismutase and glutathione activities. HG conditions markedly increased the release of interleukin (IL)-1β and IL-18 and upregulated their protein expression and activation of the nuclear factor-kappa B (NF-κB) signaling pathway, whereas β-asarone reversed these effects. Moreover, expression levels of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome multiprotein complex molecules, including thioredoxin-interacting protein, NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, and cysteinyl aspartate-specific proteinase-1, were increased in ARPE-19 cells under HG conditions. However, their expression levels remained similar to those in the control group in the presence of β-asarone. Therefore, β-asarone protects RPE cells from HG-induced injury by blocking ROS generation and NF-κB/NLRP3 inflammasome activation, indicating its potential as a therapeutic agent for DR treatment.

In Vitro Evaluation of the Antiamoebic Activity of Kaempferol against Trophozoites of Entamoeba histolytica and in the Interactions of Amoebae with Hamster Neutrophils.

Entamoeba histolytica (E. histolytica) is a parasite in humans that provokes amoebiasis. The most employed drug is metronidazole (MTZ); however, some studies have reported that this drug induces genotoxic effects. Therefore, it is necessary to explore new compounds without toxicity that can eliminate E. histolytica. Flavonoids are polyphenolic compounds that have demonstrated inhibition of growth and dysregulation of amoebic proteins. Despite the knowledge acquired to date, action mechanisms are not completely understood. The present work evaluates the effect of kaempferol against E. histolytica trophozoites and in the interactions with neutrophils from hamster, which is a susceptibility model. Our study demonstrated a significant reduction in the amoebic viability of trophozoites incubated with kaempferol at 150 μM for 90 min. The gene expression analysis showed a significant downregulation of Pr (peroxiredoxin), Rr (rubrerythrin), and TrxR (thioredoxin reductase). In interactions with amoebae and neutrophils for short times, we observed a reduction in ROS (reactive oxygen species), NO (nitric oxide), and MPO (myeloperoxidase) neutrophil activities. In conclusion, we confirmed that kaempferol is an effective drug against E. histolytica through the decrease in E. histolytica antioxidant enzyme expression and a regulator of several neutrophil mechanisms, such as MPO activity and the regulation of ROS and NO.

Extracorporeal photopheresis and the cellular mechanisms: Effects of 8-methoxypsoralen and UVA treatment on red blood cells, platelets and reactive oxygen species.

Extracorporeal photopheresis (ECP) is a widespread cellular therapy for graft-versus-host disease, autoimmune diseases and Sézary disease. One of the main effects of ECP is the apoptosis of leukocytes, but the therapeutic mechanisms are not completely known. The aim of this study was to investigate the effects on red blood cells, platelets and the induction of reactive oxygen species. We used human cells from healthy blood donors to simulate in vitro the composition in an apheresis bag. Cells were treated with 8-methoxypsoralen (8-MOP) and UVA. Red blood cell stability, platelet activity and induction of reactive oxygen species were analysed. After 8-MOP and UVA treatment, the red blood cells showed high cell integrity with low levels of eryptosis and no increase of free haemoglobin or red blood cell distribution width (RDW). Red blood cell immune-associated antigens CD59 and CD147 were hardly affected by the treatment. Platelet glycoproteins CD41, CD62P and CD63 indicated strong platelet activation after 8-MOP and UVA treatment. Reactive oxygen species were slightly but not significantly induced by the treatment. The effect of the ECP therapy is probably not exclusively mediated by leukocytes. Platelet activation is another striking effect caused by the treatment of the apheresis product with 8-MOP/UVA. However, since we could hardly identify any evidence for eryptosis or haemolysis, it is unlikely that red blood cell eryptosis is part of the therapeutic mechanism. Further research on this topic seems to be promising.

Purification and characterization of a serine protease from organic dust and elucidation of its inductive effects on lung inflammatory mediators.

Organic dust inhalation is associated with the development of respiratory diseases. Serine protease activities in organic dusts were previously reported to contribute to the induction of lung inflammatory mediators however, the identities of the proteases and the mechanisms by which they induce inflammatory mediators are unknown. The goal of this study was to purify and characterize serine protease(s) from organic dust and elucidate mechanisms by which they induce lung inflammatory mediators. A serine protease was purified from poultry organic dust by benzamidine-agarose affinity chromatography. Mass spectrometry and amino-terminal sequence analysis identified the purified protease as chicken trypsin II-P29. Purified protease induced proinflammatory cytokine levels in Beas2B and NHBE epithelial and THP-1 macrophage cells. Treatment with the purified protease increased cellular and mitochondrial reactive oxygen species (ROS) generation. Induction of inflammatory mediators and ROS were suppressed by serine protease inhibitors and antioxidants. Purified protease activated protein kinase C (PKC), mitogen-activated protein kinase (MAPK)1/3 and MAPK14 signaling, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (Stat-3), and chemical inhibitors targeting these pathways suppressed induction of inflammatory mediators. Calcium mobilization studies showed that the purified protease activated protease-activated receptors (PAR) F2R, F2RL1, F2RL2, F2RL3, and F2R and F2RL1 knockdown suppressed the induction of inflammatory mediators. Intranasal instillation of purified protease increased lung chemokine (C-X-C motif) ligand (CXCL)1, interleukin (IL)-6, and tumor necrosis factor (TNF) levels in mice. Our studies have shown that chicken trypsin is a proinflammatory constituent of poultry organic dust, and induces lung inflammatory mediators via increased ROS and PAR activation in a cell signaling pathway involving PKC, MAPK1/3 and MAPK14, and NF-κB and Stat-3.NEW & NOTEWORTHY Inhalation of dust in industrial agricultural operations is linked to the development of lung diseases. Our studies have isolated for the first time a trypsin protease from poultry farm dust and have shown that it stimulates lung inflammation. The protease stimulates the production of oxidants and cell signaling pathways to increase inflammatory mediator production. Targeting trypsin protease in poultry farm environment may be a useful strategy to counter the harmful effects of dust.

Natural compound chaetocin induced DNA damage and apoptosis through reactive oxygen species-dependent pathways in A549 lung cancer cells and in vitro evaluations.

There is an urgent need for potential pharmaceutics for lung cancer treatment due to the increased number of lung cancer deaths and the resistance of cancer cells to present therapeutics. The present work aims to discover the anticancer potential of the natural compound chaetocin as a therapeutic for lung cancer treatment. Results showed the significance of chaetocin-induced cell growth inhibition by the expression of G2 /M phase arrest and reactive oxygen species (ROS) dependent apoptosis in A549 lung cancer cells. Results concluded that chaetocin could produce ROS and nuclear damage against A549 lung cancer cells. Interestingly, chaetocin exhibits a significant level of CD47 that down-regulates the expression of CD47 at mRNA levels. PBMC biocompatibility study revealed that chaetocin is non-toxic to normal cells. Overall, experimental results suggested that chaetocin induces A549 cell apoptosis, by causing ROS and nuclear damage activation pathways. In the future, chaetocin might be an effective bio-safe anticancer agent for lung cancer treatments.

Engineering Antioxidant Surfaces for Titanium-Based Metallic Biomaterials.

Prolonged inflammation induced by orthopedic metallic implants can critically affect the success rates, which can even lead to aseptic loosening and consequent implant failure. In the case of adverse clinical conditions involving osteoporosis, orthopedic trauma and implant corrosion-wear in peri-implant region, the reactive oxygen species (ROS) activity is enhanced which leads to increased oxidative stress. Metallic implant materials (such as titanium and its alloys) can induce increased amount of ROS, thereby critically influencing the healing process. This will consequently affect the bone remodeling process and increase healing time. The current review explores the ROS generation aspects associated with Ti-based metallic biomaterials and the various surface modification strategies developed specifically to improve antioxidant aspects of Ti surfaces. The initial part of this review explores the ROS generation associated with Ti implant materials and the associated ROS metabolism resulting in the formation of superoxide anion, hydroxyl radical and hydrogen peroxide radicals. This is followed by a comprehensive overview of various organic and inorganic coatings/materials for effective antioxidant surfaces and outlook in this research direction. Overall, this review highlights the critical need to consider the aspects of ROS generation as well as oxidative stress while designing an implant material and its effective surface engineering.

Amorphous/crystalline Cu1.5Mn1.5O4 with rich oxygen vacancies for efficiently photothermocatalytic mineralization of toluene

Searching a photothermal catalyst for significantly boosting photothermocatalytic mineralization of volatile organic compounds (VOCs) still remains a challenge. Herein, an amorphous/crystalline Cu1.5Mn1.5O4 catalyst with rich oxygen vacancies was firstly fabricated for photothermal mineralization of toluene. Compared to crystalline Cu1.5Mn1.5O4 samples, amorphous/crystalline Cu1.5Mn1.5O4 catalyst exhibited a more superior photothermal catalytic activity (92.3% toluene conversion and 82.9% CO2 yield) and stability. The collective experimental studies confirmed that oxygen vacancies could contribute to photothermal conversion capacity and low temperature reducibility of amorphous/crystalline Cu1.5Mn1.5O4, enhanced the activation of reactive oxygen species and the deep oxidation of toluene under full-spectrum light. In the meantime, visible light played an auxiliary role in toluene oxidation. Moreover, the possible photothermal reaction mechanism of toluene was investigated by in situ infrared spectroscopy technique. This study can provide new ideas for application of amorphous/crystalline bimetallic oxides in photothermal mineralization of VOCs.

Reduction of high glucose-induced oxidative injury in human retinal pigment epithelial cells by sarsasapogenin through inhibition of ROS generation and inactivation of NF-κB/NLRP3 inflammasome pathway.

Hyperglycemia-induced accumulation of reactive oxygen species (ROS) is a major risk factor for diabetic retinopathy (DR). Sarsasapogenin is a natural steroidal saponin that is known to have excellent antidiabetic effects and improve diabetic complications, but its potential efficacy and mechanism for DR are unknown. The current study was designed to explore whether sarsasapogenin inhibits hyperglycemia-induced oxidative stress in human retinal pigment epithelial (RPE) ARPE-19 cells and to elucidate the molecular mechanisms. To mimic hyperglycemic conditions, ARPE-19 cells were cultured in medium containing high glucose (HG). The suppressive effects of sarsasapogenin on HG-induced cell viability reduction, apoptosis and ROS production were investigated. In addition, the relevance of the nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway was explored to investigate the mechanism of antioxidant and anti-inflammatory activity of sarsasapogenin. Sarsasapogenin significantly alleviated cytotoxicity and apoptosis in HG-treated ARPE-19 cells through inhibition of intracellular ROS generation. Sarsasapogenin also effectively attenuated HG-induced excess accumulation of mitochondrial superoxide, reduction of glutathione content, and inactivation of manganese superoxide dismutase and glutathione peroxidase. The HG condition markedly increased the expression and maturation of interleukin (IL)-1β and IL-18 through the activation of the NF-kB signaling pathway, whereas sarsasapogenin reversed these effects. Moreover, although the expression of NLRP3 inflammasome multiprotein complex molecules was increased in ARPE-19 cells cultured under HG conditions, their levels remained similar to the control group in the presence of sarsasapogenin. Sarsasapogenin could protect RPE cells from HG-induced injury by inhibiting ROS generation and NF-κB/NLRP3 inflammasome pathway, suggesting its potential as a therapeutic agent to improve the symptoms of DR.

Mitofusin2 Ameliorated Endoplasmic Reticulum Stress and Mitochondrial Reactive Oxygen Species Through Maintaining Mitochondria-Associated Endoplasmic Reticulum Membrane Integrity in Cisplatin-Induced Acute Kidney Injury.

Aims: This study investigated the regulatory effect of Mitofusin2 (Mfn2) on mitochondria-associated endoplasmic reticulum membrane (MAM) integrity and cellular injury in cisplatin-induced acute kidney injury (CP-AKI). Results: CP-AKI mice exhibited decreased expression of Mfn2, increased expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), abnormal mitochondrial morphology, and reduced MAMs integrity, accompanied by the activation of mitochondrial reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress (inositol-requiring enzyme 1 [IRE1] and PERK pathways). In in vitro studies, CP-induced mitochondrial ROS, ER-stress activation, and increased apoptosis were accompanied by the downregulation of Mfn2 and MAMs integrity reduction in Boston University mouse proximal tubular cells (BUMPT) and human proximal tubular epithelial cells (HK-2). Pretreatment of BUMPT cells with the Mfn2 plasmid partially restored the integrity of MAMs, negatively controlled IRE1 and PERK pathways, and inhibited cell apoptosis. In contrast, ER-stress and MAMs integrity violations were increased after Mfn2 small-interfering RNA (siRNA) treatment in HK-2 cells under CP treatment. Coimmunoprecipitation analysis demonstrated that Mfn2 interacted with PERK and IRE1. Furthermore, the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acadesine (AICAR), had a similar effect to Mfn2 plasmid in the regulation of ER stress and MAMs. Conversely, the ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), had no effect on the expression of Mfn2 and MAMs integrity. Innovation and Conclusion: This is the first study to explore the association between MAMs, ER stress, and Mfn2 in CP-AKI. Downregulation of Mfn2 expression abolished the MAMs integrity, and induced ER stress, mitochondrial ROS, and tubular cell apoptosis. This suggests that the Mfn2-MAMs pathway is a potential therapeutic target in CP-AKI. Antioxid. Redox Signal. 40, 16-39. The Ethical Registration number of animal experiment in this study was CSU-2022-01-0095.

Cellular and Non-cellular Antioxidant Properties of Vitamin E-Loaded Metallic-Quercetin/Polycaprolactone Nanoparticles for the Treatment of Melanogenesis.

Inhibition of melanogenesis by quercetin and vitamin E is extensively reported in the literature, independently, with limitations in antioxidant potential owing to less permeation, solubility, decreased bioavailability, and reduced stability. Thus, the aim of the present study was to synthesize a novel complex of metal ions (copper and zinc) with quercetin to enhance antioxidant properties which were confirmed by docking studies. Polycaprolactone-based nanoparticles of the synthesized complex (PCL-NPs, Q-PCL-NPs, Zn-Q-PCL-NPs, Cu-Q-PCL-NPs) were made later loaded with vitamin E which made the study more interesting in enhancing antioxidant profile. Nanoparticles were characterized for zeta size, charge, and polydispersity index, while physiochemical analysis of nanoparticles was strengthened by FTIR. Cu-Q-PCL-NPs-E showed maximum in vitro release of vitamin E, i.e., 80 ± 0.54%. Non-cellular antioxidant effect by 2,2-diphenyl-1-picrylhydrazyl was observed at 93 ± 0.23% in Cu-Q-PCL-NPs-E which was twofold as compared to Zn-Q-PCL-NPs-E. Michigan Cancer Foundation-7 (MCF-7) cancer cell lines were used to investigate the anticancer and cellular antioxidant profile of loaded and unloaded nanoparticles. Results revealed reactive oxygen species activity of 90 ± 0.32% with the addition of 89 ± 0.64% of its anticancer behavior shown by Cu-Q-PCL-NPs-E after 6 and 24h. Similarly, 80 ± 0.53% inhibition of melanocyte cells and 95 ± 0.54% increase of keratinocyte cells were also shown by Cu-Q-PCL-NPs-E that confirmed the tyrosinase enzyme inhibitory effect. Conclusively, the use of zinc and copper complex in unloaded and vitamin E-loaded nanoparticles can provide enhanced antioxidant properties with inhibition of melanin, which can be used for treating diseases of melanogenesis.

Evaluation of the Effect of Plectranthus amboinicus L. Leaf Extracts on the Bacterial Antioxidant System and Cell Membrane Integrity of Pseudomonas aeruginosa PA01 and Staphylococcus aureus NCTC8325.

Plectranthus amboinicus (Indian borage) has been extensively studied for its medicinal properties, which can be exploited to develop new antimicrobial therapeutics. The current study investigated the effect of Plectranthus amboinicus leaf extracts on the catalase activity, reactive oxygen species, lipid peroxidation, cytoplasmic membrane permeability, and efflux pump activity in S. aureus NCTC8325 and P. aeruginosa PA01. As the enzyme catalase protects bacteria against oxidative stress, disruption of its activity creates an imbalance in reactive oxygen species (ROS) levels, which subsequently oxidizes lipid chains, leading to lipid peroxidation. In addition, bacterial cell membranes are a potential target for new antibacterial agents, as efflux pump systems play a crucial role in antimicrobial resistance. Upon exposure of the microorganisms to Indian borage leaf extracts, the observed catalase activity decreased by 60% and 20% in P. aeruginosa and S. aureus, respectively. The generation of ROS can cause oxidation reactions to occur within the polyunsaturated fatty acids of the lipid membranes and induce lipid peroxidation. To investigate these phenomena, the increase in ROS activity in P. aeruginosa and S. aureus was studied using H2DCFDA, which is oxidized to 2',7'-dichlorofluorescein (DCF) by ROS. Furthermore, the concentration of lipid peroxidation product (malondialdehyde) was assessed using the Thiobarbituric acid assay and was shown to increase by 42.4% and 42.5% in P. aeruginosa and S. aureus, respectively. The effect of the extracts on the cell membrane permeability was monitored using diSC3-5 dye and it was observed that the cell membrane permeability of P. aeruginosa increased by 58% and of S. aureus by 83%. The effect on efflux pump activity was investigated using Rhodamine-6-uptake assay, which displayed a decrease in efflux activity of 25.5% in P. aeruginosa and 24.2% in S. aureus after treatment with the extracts. This combination of different methods to study various bacterial virulence factors provides a more robust, mechanistic understanding of the effect of P. amboinicus extracts on P. aeruginosa and S. aureus. This study thus represents the first report of the assessment of the effect of Indian borage leaf extracts on bacterial antioxidant systems and bacterial cell membranes, and can facilitate the future development of bacterial resistance modifying agents derived from P. amboinicus.

Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells

Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However, we know little about the effects nor mechanisms of FPM on APC. Here, using human APC A549 cells, we found that FPM resulted in blockade of autophagic flux, redox imbalance and oxidative stress, mitochondrial fragmentation, increased mitophagy and impaired mitochondrial respiration. Further we showed that activation of JNK signaling (c-Jun N-terminal kinase) and excessive ROS (reactive oxygen species) release contribute to these adverse effects, with the former being upstream of the latter. More importantly, we found that scavenging ROS or inhibiting JNK activation could restore those effects as well as ameliorate FPM-induced inhibition of cell proliferation, and epithelial-mesenchymal transformation (EMT) in A549 cells. Taken together, our findings indicate that FPM leads to toxicity in alveolar type II cells via JNK activation, and JNK-targeting or antioxidant strategies might be beneficial for prevention or treatment of FPM-related pulmonary diseases.

Dual Functional Titanium Hydride Particles for Anti‐Ultraviolet and Anti‐Oxidant Applications

AbstractTiO2 is a typical anti‐ultraviolet agent in sunscreen cream, but it suffers from a lack of anti‐oxidant activity for scavenging reactive oxygen species. Other traditional sunscreen ingredients, such as C60 and ferulic acid, have moderate antioxidant and UV protection capabilities, and the products do not provide further UV protection. Herein, titanium hydride (TiH1.97) particles with dual functions of anti‐oxidant and anti‐ultraviolet are presented as an active material to remove the highly oxidizing and harmful hydroxide free radicals from the skin surface. Owing to the active hydrogen in TiH2, it shows great potential to eliminate hydroxyl radicals, and the rate is roughly proportional to the exposed surface area (50% /20 min). Together with the biocompatibility of the in situ formed TiO2, which has a strong ability to absorb ultraviolet light during OH radical scavenging. At the same time, adding titanium hydride to sunscreen also enhances sun protection. The SPF value of sunscreen containing 1% titanium hydride and 20% titanium dioxide can reach 31.8, which exceeds the 20% titanium dioxide (15) by more than twofold. Therefore, titanium hydride with anti‐ultraviolet and antioxidant functions can be regarded as a promising and safe ingredient for sunscreen cream.

The Eco-Immunological Relevance of the Anti-Oxidant Response in Invasive Molluscs.

Reactive oxygen species (ROS) are volatile and short-lived molecules playing important roles in several physiological functions, including immunity and physiological adaptation to unsuitable environmental conditions. In an eco-immunological view, the energetic costs associated with an advantageous metabolic apparatus able to cope with wide changes in environmental parameters, e.g., temperature range, water salinity or drought, could be further balanced by the advantages that this apparatus may also represent in other situations, e.g., during the immune response. This review provides an overview of molluscs included in the IUCN list of the worst invasive species, highlighting how their relevant capacity to manage ROS production during physiologically challenging situations can also be advantageously employed during the immune response. Current evidence suggests that a relevant capacity to buffer ROS action and their damaging consequences is advantageous in the face of both environmental and immunological challenges, and this may represent a trait for potential invasiveness. This should be considered in order to obtain or update information when investigating the potential of the invasiveness of emerging alien species, and also in view of ongoing climate changes.

Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer.

Treatment of late-stage lung cancers remains challenging with a five-year survival rate of 8%. Immune checkpoint blockers (ICBs) revolutionized the treatment of non-small cell lung cancer (NSCLC) by reactivating anti-tumor immunity. Despite achieving durable responses, ICBs are effective in only 20% of patients due to immune resistance. Therefore, synergistic combinatorial approaches that overcome immune resistance are currently under investigation. Herein, we studied the immunomodulatory role of Withaferin A (WFA)-a herbal compound-and its effectiveness in combination with an ICB for the treatment of NSCLC. Our in vitro results show that WFA induces immunogenic cell death (ICD) in NSCLC cell lines and increases expression of the programmed death ligand-1 (PD-L1). The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process. Further, we found that a combination of WFA and α-PD-L1 significantly reduced tumor growth in an immunocompetent tumor model. Our results showed that WFA increases CD-8 T-cells and reduces immunosuppressive cells infiltrating the tumor microenvironment. Administration of NAC partially inhibited the anti-tumor response of the combination regimen. In conclusion, our results demonstrate that WFA sensitizes NSCLC to α-PD-L1 in part via activation of ROS.

Oxidative damage contributes to bisphenol S-induced development block at 2-cell stage preimplantation embryos in mice through inhibiting of embryonic genome activation

Although bisphenol S (BPS), as a bisphenol A (BPA) substitute, has been widely used in the commodity, it is embryotoxic in recent experiments. Nowadays, it remains unclear how BPS affects preimplantation embryos. Here, my team investigated the effects of BPS on preimplantation embryos and the possible molecular mechanisms in mice. The results showed that 10–6 mol/L BPS exposure delayed the blastocysts stage, and exposure to 10–4 mol/L BPS induced 2-cell block in mice preimplantation embryos. A significant increase in reactive oxygen species (ROS) level and antioxidant enzyme genes Sod1, Gpx1, Gpx6, and Prdx2 expression were shown, but the level of apoptosis was normal in 2-cell blocked embryos. Further experiments demonstrated that embryonic genome activation (EGA) specific genes Hsp70.1 and Hsc70 were significantly decreased, which implied that ROS and EGA activation have the potential to block 2-cell development. Antioxidant enzymes, including superoxide dismutase (SOD), coenzyme Q10 (CoQ10), and folic acid (FA) were used to further explore the roles of ROS and EGA in 2-cell block. Only 1200 U/mL SOD was found to alleviate the phenomenon of 2-cell block, reduce oxidative damage, and restore the expression of EGA-specific genes Hsp70.1 and Hsc70. Conclusively, this study demonstrates for the first time that BPS can induce 2-cell block, which is mainly mediated by ROS aggregation and results in the failure of EGA activation.

Photodynamic inactivation of spoilers Pseudomonas lundensis and Brochothrix thermosphacta by food-grade curcumin and its application on ground beef

This study evaluated the bactericidal effects of curcumin-mediated photodynamic inactivation (PDI) combined with citric acid on meat spoilage bacteria, and their preservative effects of refrigerated beef. After treatment of PDI (60 μM curcumin and 33.01 J/cm2) combined with 0.5 mg/mL citric acid, the populations of Pseudomonas lundensis and Brochothrix thermosphacta in PBS solution were reduced by 3.07 and 6.14 log CFU/mL, respectively, compared to 0.31 and 1.39 log CFU/mL for PDI. Combined treatment enhanced reactive oxygen species (ROS) activity in the two strains, and damaged their cell morphology, especially B. thermosphacta. With increasing curcumin concentration, the growth rate of spoilage bacteria was significantly inhibited (P < 0.05), and the changes of dominant spoilage species in bacterial community were retarded in aerobic-packaged and vacuum-packaged ground beef at 4 °C. Compared to the control, trichloroacetic acid-soluble peptide and total volatile basic nitrogen production were greatly restrained, and changes in pH values and brown color were apparently reduced for the combined treatment, which could extend the shelf life by 2 days. These results suggested the synergistic potency of PDI combined with citric acid against spoilage bacteria in meat products.Industrial relevance: The proliferation and spread of some psychrotrophs are major causes of quality deterioration and cross-contamination in fresh meat during cold chain. This study revealed that photosensitized curcumin combined with citric acid significantly decreased the survival of two psychrotrophic spoilage bacteria and extended the shelf-life of ground beef. Thus, curcumin-based PDI provides a new insight for the development of efficient and economic preservation in the meat processing industry.

Chronic Injury of Mice Bone Marrow Multipotent Hematopoietic Progenitor Cells Induced by Ionizing Radiation

To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation. Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed. Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05). Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.