Low Levels Of Reactive Oxygen Species Research Articles

Vitamin k3-Loaded Magnetic Nanoparticle-Mediated Synergistic Magnetothermodynamic Therapy Evokes Massive ROS and Immune Modulation for Augmented Antitumor Potential.

Magnetic nanoparticle (MNP)-mediated magnetic hyperthermia (MHT) under an alternating magnetic field (AMF) causes tumor regression via reactive oxygen species (ROS) generation. However, less therapeutic efficacy has been reported due to the generation of low levels of ROS in a hypoxic tumor microenvironment. Therefore, improved treatments are required to generate relatively high levels of ROS to promote irreversible oxidative damage to the tumor cells. Herein, we report a magnetothermodynamic (MTD) therapy, as a robust and versatile approach for cancer treatment, by combining the magnetothermodynamic-related ROS and heat-related immunological effect in order to overcome the aforementioned obstacle. The synergistic therapy was achieved by the development of vitamin k3 (Vk3)-loaded copper zinc ferrite nanoparticles (Vk3@Si@CuZnIONPs) as an efficient MTD agent. The in vitro results unveiled that enhanced ROS production under the influence of AMF is a predominant aspect in yielding an assertive anticancer response. The in vivo antitumor response was assessed in an ectopic tumor model of A549 lung adenocarcinoma by MTD. The tumor inhibition rate of 69% was achieved within 20 days of MTD treatment, exhibiting complete tumor eradication within 30 days. The validation of antitumor response was marked by severe apoptosis (TUNEL, Caspase-3) in the Vk3@Si@CuZnIONPs + AMF-treated group. The higher expression level of heat shock proteins and proinflammatory cytokines (IL-6, TNF-α, IL-1α, IL-1β) was speculated to play a role in the activation of immune response for faster tumor regression in the MTD-treated group. Therefore, by implementing a dual ROS and heat-mediated immunogenic effect, the antitumor efficiency of future cancer magnetotherapies will be greatly enhanced.

The Mechanosensitive Piezo1 Channel Mediates Mechanochemical Transmission in Myopic Eyes.

To identify the expression of the mechanosensitive ion channel Piezo1 in the retina of guinea pigs with form deprivation myopia (FDM) and to investigate mechanisms by which Piezo1 channels might regulate myopia. Sixty 3-week-old guinea pigs were divided into four groups randomly: normal control, FDM, FDM + vehicle control (DMSO), and FDM + Piezo1 inhibitor (GsMTx4). Measurements of spherical equivalent (SE) and axial length (AL) of the guinea pig were taken using retinoscopy and A-scan ultrasound examination, respectively. Location of Piezo1 protein was determined using immunohistochemistry. The histological structure and thickness changes of the guinea pig retina were observed by hematoxylin and eosin. Expression of Piezo1 in the retina was detected using quantitative RT-PCR and Western blot. Reactive oxygen species (ROS) levels in the retina were measured using flow cytometry. After 4 weeks of form deprivation, the FDM group exhibited a significantly increased myopic degree and axial length compared with the normal control group (all P < 0.001), and had higher expression levels of Piezo1 and ROS than the normal control group (P < 0.001 and P = 0.002, respectively). Piezo1 protein expression was down-regulated in guinea pigs given GsMTx4 compared with the DMSO group (P = 0.037). Additionally, the GsMTx4 group showed lower myopic degree (P < 0.001) and lower ROS levels (P = 0.019) compared with the DMSO group. The Piezo1 channel may be activated in the retinas of FDM guinea pigs and be involved in the development of myopia by regulating intraocular ROS levels.

Relationship among seminal antigenicity, antioxidant status and metabolically active sperm from Holstein-Friesian (Bos taurus) bulls

Sperm antigenicity has been implicated as a regulatory factor for acquiring fertilizing competence in the female reproductive tract. Overt immune response against the sperm proteins leads to idiopathic infertility. Hence, the aim of the study was to evaluate the influence of the auto-antigenic potential of sperm on the antioxidant status, metabolic activities and reactive oxygen species (ROS) in bovine. Semen from Holstein-Friesian bulls (n = 15) was collected and classified into higher (HA, n = 8) and lower (LA, n = 7) antigenic groups based on micro-titer agglutination assay. The neat semen was subjected to the evaluation of bacterial load, leukocyte count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lipid peroxidation (LPO) levels. Antioxidant activities in seminal plasma and intracellular ROS levels in the post-thawed sperm were estimated. The number of leukocytes was lower (p < .05) in the HA than the LA semen. The percentage of metabolically active sperm was higher (p < .05) in HA than the LA group. The activities of total non-enzymatic antioxidant, superoxide dismutase (SOD) and catalase (CAT) were higher (p < .05) while glutathione peroxidase activity was lower (p < .05) in the seminal plasma of LA group. The LPO levels of neat sperm and the percentage sperm positive for intracellular ROS in the cryopreserved sample were lower (p < .05) in the HA group. Auto-antigenic levels were positively correlated with the percentage of metabolically active sperm (r = 0.73, p < .01). However, the seminal auto-antigenicity was negatively (p < .05) correlated with the levels of SOD (r=–0.66), CAT (r=–0.72), LPO (r=–0.602) and intracellular ROS (r=–0.835). The findings were represented in graphical abstract. It is inferred that the higher auto-antigenic levels protect the quality of bovine semen by promoting sperm metabolism and lowering ROS and LPO levels.

Alpha-Tocopherol Significantly Improved Squalene Production Yield of Aurantiochytrium sp. TWZ-97 through Lowering ROS levels and Up-Regulating Key Genes of Central Carbon Metabolism Pathways.

Media supplementation has proven to be an effective technique for improving byproduct yield during microbial fermentation. This study explored the impact of different concentrations of bioactive compounds, namely alpha-tocopherol, mannitol, melatonin, sesamol, ascorbic acid, and biotin, on the Aurantiochytrium sp. TWZ-97 culture. Our investigation revealed that alpha-tocopherol was the most effective compound in reducing the reactive oxygen species (ROS) burden, both directly and indirectly. Adding 0.7 g/L of alpha-tocopherol led to an 18% improvement in biomass, from 6.29 g/L to 7.42 g/L. Moreover, the squalene concentration increased from 129.8 mg/L to 240.2 mg/L, indicating an 85% improvement, while the squalene yield increased by 63.2%, from 19.82 mg/g to 32.4 mg/g. Additionally, our comparative transcriptomics analysis suggested that several genes involved in glycolysis, pentose phosphate pathway, TCA cycle, and MVA pathway were overexpressed following alpha-tocopherol supplementation. The alpha-tocopherol supplementation also lowered ROS levels by binding directly to ROS generated in the fermentation medium and indirectly by stimulating genes that encode antioxidative enzymes, thereby decreasing the ROS burden. Our findings suggest that alpha-tocopherol supplementation can be an effective method for improving squalene production in Aurantiochytrium sp. TWZ-97 culture.

Salicylic acid treatment delayed the browning development in the pericarp of fresh longan by regulating the metabolisms of ROS and membrane lipid

Longans is popular among consumers because of its rich nutritional value, but it is prone to pericarp browning as it is harvested in the high-temperature season. This work was to investigate the effects of salicylic acid (SA) on the metabolisms of reactive oxygen species (ROS) and membrane lipid and their relationship with pericarp browning of postharvest longans. ‘Fuyan’ longans were soaked in the solution of 0.3 g L-1 SA for 5 min, then stockpiled at 28 °C. The results showed that, the pericarp browning index in SA-treated fruit was 42% lower than that in the control fruit at day 5 of storage. Meanwhile, SA treatment reduced the damage severity of cell membrane structure, and maintained a low level of cell membrane permeability, which was 25% lower than that in the control fruit at day 5 of storage. Additionally, compared to the control fruit, SA-treated longans displayed higher levels of pericarp L*, flavonoid, chlorophyll, carotenoid, total phenolics, and anthocyanin, higher activities of pericarp superoxide dismutase, catalase, and ascorbate peroxidase, higher values of pericarp reducing power and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, and higher amounts of pericarp ascorbic acid and glutathione, but lower levels of pericarp ROS and malondialdehyde. Moreover, SA-treated samples exhibited lower activities of pericarp phospholipase, lipase, and lipoxygenase, lower levels of pericarp phosphatidic acid and saturated fatty acids (SFA), but higher values of pericarp phosphatidylcholine, phosphatidylinositol, and unsaturated fatty acids (USFA), higher index of USFA, and higher ratio of USFA to SFA. These findings corroborated that SA delayed-browning occurrence in the pericarp of fresh longans was because SA enhanced the capacity to remove ROS, and reduced ROS accumulation and the membrane lipid degradation, thus maintaining the cellular membrane structure, reducing the degradation of pigments, and allowing the fresh longans to maintain a better appearance. Consequently, SA could be an effective means for suppressing pericarp browning and improving the commercial value of fresh longans.

Effects of β-Nicotinamide Mononucleotide, Berberine, and Cordycepin on Lipid Droplet Content and Developmental Ability of Vitrified Bovine Oocytes.

Oocyte vitrification is crucial for livestock reproduction, germplasm conservation, and human-assisted reproduction, but the overabundance of lipids is highly detrimental to oocyte development. It is necessary to reduce the lipid droplet content of oocytes before cryopreservation. This study analyzed the impact of β-nicotinamide mononucleotide (NMN), berberine (BER), or cordycepin (COR) on various aspects of bovine oocytes, including lipid droplet content and the expression levels of genes related to lipid synthesis in bovine oocytes, development ability, reactive oxygen species (ROS), apoptosis, and the expression levels of genes associated with endoplasmic reticulum (ER) stress, and mitochondrial function in vitrified bovine oocytes. The results of our study indicated that 1 μM NMN, 2.5 μM BER, and 1 μM COR were effective in reducing the lipid droplet content and suppressing the expression levels of genes involved in lipid synthesis in bovine oocytes. Our findings showed that the vitrified bovine oocytes treated with 1 μM of NMN had a significantly higher survival rate and better development ability compared to the other vitrified groups. Additionally, 1 μM NMN, 2.5 μM BER, and 1 μM COR decreased the levels of ROS and apoptosis, decreased the mRNA expression levels of genes involved in ER stress and mitochondrial fission but increased the mRNA expression levels of genes associated with mitochondrial fusion in the vitrified bovine oocytes. Our study results suggested that 1 μM NMN, 2.5 μM BER, and 1 μM COR effectively decreased the lipid droplet content and enhanced the development ability of vitrified bovine oocytes by lowering ROS levels, reducing ER stress, regulating mitochondrial function, and inhibiting apoptosis. Furthermore, the results showed that 1 μM NMN was more effective than 2.5 μM BER and 1 μM COR.

Oxidative stress and inflammation: the root causes of aging

Oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] are generated by mitochondria during adenosine triphosphate synthesis, and catalytic activities of cytochrome P450, nicotinamide adenine dinucleotide phosphate oxidases (NOXs), cyclooxygenases, and nitric oxide synthases during drug catabolism, phagocytosis, and acute inflammation. Under normal circumstances, low levels of ROS and RNS provide redox signalings that control many essential physiological processes. As age progresses ROS and RNS increase excessively due to dysfunctional mitochondria, dysregulated NOX, and other free-radical generating sources, leading to oxidative stress, which causes oxidation and denaturation of key cellular components including DNA, proteins, and lipids, which become abnormal, constituting damage-associated molecular pattern (DAMP), recognized as ‘non-self’ by immune cells, leading to inflammation which is mediated by nuclear factor kappa B-inflammasome, p38-c-Jun N-terminal kinase and Janus kinase-signal transducer and activator of transcription pathways. DAMPs are continuously released from damaged and senescent cells, causing an otherwise normally transient inflammation turning into systemic chronic inflammation, the root cause of aging and age-associated diseases (AADs). Cells restore redox balance by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway that induces the synthesis and release of antioxidation molecules and enzymes including haem oxygenase-1, which also inhibits the three inflammatory pathways. Furthermore, upregulation of autophagy (AP) can get rid of abnormal molecules, prevent the generation of DAMPs, and attenuate inflammation. Both AP and Nrf2 signalings decrease with age. The upregulations of Nrf2, AP, and downregulation of inflammation are controlled by sensors of energy and stress levels, i.e., adenosine monophosphate-activated protein kinase, silent information regulator 1, and Sestrins, as well as the extracellular matrix, while mammalian targets for rapamycin complex 1, a nutrient sensor, act in the opposite direction. If the balance of these sensor systems becomes dysregulated, aging process accelerates, and the risk of AADs increases.

The Regulatory Mechanism of Cold Plasma in Relation to Cell Activity and Its Application in Biomedical and Animal Husbandry Practices.

As an innovative technology in biological applications, cold plasma is widely used in oral treatment, tissue regeneration, wound healing, and cancer therapy, etc., because of the adjustable composition and temperature which allow the plasma to react with bio-objects safely. Reactive oxygen species (ROS) produced by cold plasma regulate cell activity in an intensity- and time-dependent manner. A low level of ROS produced by cold plasma treatment within the appropriate intensities and times promotes proliferation of skin-related cells and increases angiogenesis, which aid in the acceleration of the wound healing process, while a high level of ROS produced by cold plasma treatment performed at a high intensity or over a long period of time inhibits the proliferation of endothelial cells, keratinocytes, fibroblasts, and cancer cells. Moreover, cold plasma can regulate stem cell proliferation by changing niche interface and producing nitric oxide directly. However, the molecular mechanism of cold plasma regulating cell activity and its potential application in the field of animal husbandry remain unclear in the literature. Therefore, this paper reviews the effects and possible regulatory mechanisms of cold plasma on the activities of endothelial cells, keratinocytes, fibroblasts, stem cells, and cancer cells to provide a theoretical basis for the application of cold plasma to skin-wound healing and cancer therapy. In addition, cold plasma exposure at a high intensity or an extended time shows excellent performances in killing various microorganisms existing in the environment or on the surface of animal food, and preparing inactivated vaccines, while cold plasma treatment within the appropriate conditions improves chicken growth and reproductive capacity. This paper introduces the potential applications of cold plasma treatment in relation to animal-breeding environments, animal health, their growth and reproduction, and animal food processing and preservation, which are all beneficial to the practice of animal husbandry and guarantee good animal food safety results.

The combination of rolipram and cilostamide improved the developmental competence of cloned porcine embryos

In vitro maturation of porcine oocytes is characterized by asynchronous cytoplasmic and nuclear maturation, leading to less competent oocytes supporting embryo development. The purpose of this study was to evaluate the combined effect of rolipram and cilostamide as cyclic Adenine monophosphate (cAMP) modulators to find the maximum cAMP levels that temporarily arrest meiosis. We determined the optimal time to maintain functional gap junction communication during pre-in vitro maturation to be four hours. Oocyte competence was evaluated by the level of glutathione, reactive oxygen species, meiotic progression, and gene expression. We evaluated embryonic developmental competence after parthenogenetic activation and somatic cell nuclear transfer. The combined treatment group showed significantly higher glutathione and lower reactive oxygen species levels and a higher maturation rate than the control and single treatment groups. Cleavage and blastocyst formation rates in parthenogenetic activation and somatic cell nuclear transfer embryos were higher in two-phase in vitro maturation than in the other groups. The relative levels of BMP15and GDF9 expression were increased in two-phase in vitro maturation. Somatic cell nuclear transfer blastocysts from two-phase in vitro maturation oocytes showed a lower level of expression of apoptotic genes than the control, indicating better pre-implantation developmental competence. The combination of rolipram and cilostamide resulted in optimal synchrony of cytoplasmic and nuclear maturation in porcine in vitro matured oocytes and there by enhanced the developmental competence of pre-implantation embryos.

Integrated enzymes activity and transcriptome reveal the effect of exogenous melatonin on the strain degeneration of Cordyceps militaris.

As a valuable medicinal and edible fungus, Cordyceps militaris has been industrialized with broad development prospects. It contains a lot of bioactive compounds that are beneficial to our health. However, during artificial cultivation, strain degeneration is a challenge that inhibits the industrialization utility of C. militaris. Exogenous melatonin (MT) can scavenge for reactive oxygen species (ROS) in fungus and can alleviate strain degeneration. To establish the significance and molecular mechanisms of MT on strain degeneration, we investigated the third-generation strain (W5-3) of C. militaris via morphological, biochemical, and transcriptomic approaches under MT treatment. Morphological analyses revealed that colony angulation of C. militaris was significantly weakened, and the aerial hypha was reduced by 60 μmol L-1 MT treatment. Biochemical analyses showed low levels of ROS and malondialdehyde (MDA), as well as increasing endogenous MT levels as exogenous MT increased. RNA-Seq revealed that compared with the control, several antioxidant enzyme-related genes were up-regulated under 60 μmol L-1 MT treatment. Among them, glutathione s-transferase genes were up-regulated by a factor of 11.04. In addition, genes that are potentially involved in cordycepin, adenosine and active compound biosynthesis for the growth and development of mycelium were up-regulated. Collectively, these findings provide the basis for further elucidation of the molecular mechanisms involved in C. militaris strain degeneration.

Maslinic acid attenuates UVB-induced oxidative damage in HFF-1 cells.

Oxidative damage is one of the major mechanisms of ultraviolet B (UVB)-induced damage to the skin. Maslinic acid (MA) is a natural compound of pentacyclic triterpene acids. It has been proved to have anti-inflammatory and antioxidant properties. This study aimed to explore the effects of MA on oxidative damage in human foreskin fibroblast cells (HFF-1) and the potential molecular mechanisms. A specific dose of UVB radiation was used to induce oxidative damage in HFF-1. Based on this, we performed measurements of cell proliferation, reactive oxygen species (ROS) levels, antioxidant enzyme activity, inflammation-related mediators, and NF-κB nuclear localization with or without the addition of MA. MA significantly promoted cell proliferation viability at 10 and 20 μM. The addition of MA 24 h before UVB irradiation was more effective at enhancing cell proliferation and also produced lower ROS levels compared to co-cultured fibroblasts and MA for 24 h after irradiation. However, there was no statistically significant difference between groups at concentrations of 10 and 20 μM. The pretreatment group with MA had elevated superoxide dismutase and catalase activities, decreased IL-6 generation, and lowered mRNA levels of IL-6, TNF-α and MMP3 in comparison with the UVB-irradiated group without additional MA. Meanwhile, the nuclear translocation of NF-κB and the degradation of IκB were inhibited by MA pretreatment. Taken together, these findings suggest that MA may alleviate UVB-induced oxidative damage in HFF-1 by inhibiting the nuclear translocation of NF-κB.

The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities

Alzheimer's disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the antioxidant response in cells. Under low ROS levels, Nrf2 is kept in the cytoplasm. However, an increase in ROS production leads to a translocation of Nrf2 into the nucleus, where it activates the transcription of several genes involved in the cells' antioxidant response. Additionally, Nrf2 activation increases autophagy function. However, in AD, the accumulation of Aβ and tau reduces Nrf2 levels, decreasing the antioxidant response. The reduced Nrf2 levels contribute to the further accumulation of Aβ and tau by impairing their autophagy-mediated turnover. In this review, we discuss the overwhelming evidence indicating that genetic or pharmacological activation of Nrf2 is as a potential approach to mitigate AD pathology.

GPR120 promotes neutrophil control of intestinal bacterial infection

ABSTRACT G-protein coupled receptor 120 (GPR 120) has been implicated in anti-inflammatory functions. However, how GPR120 regulates the neutrophil function remains unknown. This study investigated the role of GPR120 in the regulation of neutrophil function against enteric bacteria. 16S rRNA sequencing was used for measuring the gut microbiota of wild-type (WT) mice and Gpr120 −/− mice. Citrobacter rodentium infection and dextran sulfate sodium (DSS)-induced colitis models were performed in WT and Gpr120 −/− mice. Mouse peritoneal-derived primary neutrophils were used to determine the neutrophil functions. Gpr120 −/− mice showed altered microbiota composition. Gpr120 −/− mice exhibited less capacity to clear intestinal Citrobacter rodentium and more severe intestinal inflammation upon infection or DSS insults. Depletion of neutrophils decreased the intestinal clearance of Citrobacter rodentium. GPR120 agonist, CpdA, enhanced WT neutrophil production of reactive oxygen species (ROS) and extracellular traps (NETs), and GPR120-deficient neutrophils demonstrated a lower level of ROS and NETs. CpdA-treated neutrophils showed an enhanced capacity to inhibit the growth of Citrobacter rodentium, which was abrogated by the inhibition of either NETs or ROS. CpdA promoted neutrophil inhibition of the growth of commensal bacteria Escherichia coli O9:H4 and pathobiont Escherichia coli O83:H1 isolated from a Crohn’s disease patient. Mechanically, mTOR activation and glycolysis mediated GPR120 induction of ROS and NETs in neutrophils. Additionally, CpdA promoted the neutrophil production of IL-17 and IL-22, and treatment with a conditioned medium of GPR120-activated neutrophils increased intestinal epithelial cell barrier functions. Our study demonstrated the critical role of GPR120 in neutrophils in protection against enteric bacterial invasion.

Anethole improves the developmental competence of porcine embryos by reducing oxidative stress via the sonic hedgehog signaling pathway

BackgroundAnethole (AN) is an organic antioxidant compound with a benzene ring and is expected to have a positive impact on early embryogenesis in mammals. However, no study has examined the effect of AN on porcine embryonic development. Therefore, we investigated the effect of AN on the development of porcine embryos and the underlying mechanism.ResultsWe cultured porcine in vitro-fertilized embryos in medium with AN (0, 0.3, 0.5, and 1 mg/mL) for 6 d. AN at 0.5 mg/mL significantly increased the blastocyst formation rate, trophectoderm cell number, and cellular survival rate compared to the control. AN-supplemented embryos exhibited significantly lower reactive oxygen species levels and higher glutathione levels than the control. Moreover, AN significantly improved the quantity of mitochondria and mitochondrial membrane potential, and increased the lipid droplet, fatty acid, and ATP levels. Interestingly, the levels of proteins and genes related to the sonic hedgehog (SHH) signaling pathway were significantly increased by AN.ConclusionsThese results revealed that AN improved the developmental competence of porcine preimplantation embryos by activating SHH signaling against oxidative stress and could be used for large-scale production of high-quality porcine embryos.

AnAzf1 acts as a positive regulator of ochratoxin A biosynthesis in Aspergillus niger.

Aspergillus niger produces genotoxic and carcinogenic ochratoxin A (OTA) that severely threatens human and animal health. Transcription factor Azf1 is essential in regulating fungal cell development and primary metabolism. However, its effect and mechanism on secondary metabolism are unclear. Here, we characterized and deleted a Azf1 homolog gene, An15g00120 (AnAzf1), in A. niger, which completely blocked OTA production, and repressed the OTA cluster genes, p450, nrps, hal, and bzip at the transcriptional level. The results indicated that AnAzf1 was a positive regulator of OTA biosynthesis. Transcriptome sequencing results showed that the AnAzf1 deletion significantly upregulated antioxidant genes and downregulated oxidative phosphorylation genes. Enzymes involved in reactive oxygen species (ROS) scavenging, including catalase (CAT) and peroxidase (POD) were increased, and the corresponding ROS levels were decreased. Upregulation of genes (cat, catA, hog1, and gfd) in the MAPK pathway and downregulation of genes in iron homeostasis were associated with decreased ROS levels, linking the altered MAPK pathway and iron homeostasis to lower ROS levels caused by AnAzf1 deletion. Additionally, enzymes including complex I (NADH-ubiquinone oxidoreductase), and complex V (ATP synthase), as well as ATP levels, were significantly decreased, indicating impaired oxidative phosphorylation caused by the AnAzf1-deletion. During lower ROS levels and impaired oxidative phosphorylation, OTA was not produced in ∆AnAzf1. Together, these results strongly suggested that AnAzf1 deletion blocked OTA production in A. niger by a synergistic interference of ROS accumulation and oxidative phosphorylation. KEY POINTS: • AnAzf1 positively regulated OTA biosynthesis in A. niger. • Deletion of AnAzf1 decreased ROS levels and impaired oxidative phosphorylation. • An altered MAPK pathway and iron homeostasis were associated with lower ROS levels.

Quantitative proteomics reveals reduction in central carbon and energy metabolisms contributes to gentamicin resistance in Staphylococcus aureus

The emergence of antibiotic resistance greatly increases the difficulty of treating bacterial infections. In order to develop effective treatments, the underlying mechanisms of antibiotic resistance must be understood. In this study, Staphylococcus aureus ATCC6538 strain was passaged in medium with and without gentamicin and obtained lab-evolved gentamicin-resistant S. aureus (RGEN) and gentamicin-sensitive S. aureus (SGEN) strains, respectively. Data-Independent Acquisition (DIA)-based proteomics approach was applied to compare the two strains. A total of 1426 proteins were identified, of which 462 were significantly different: 126 were upregulated and 336 were downregulated in RGEN compared to SGEN. Further analysis found that reduced protein biosynthesis was a characteristic feature in RGEN, related to metabolic suppression. The most differentially expressed proteins were involved in metabolic pathways. In RGEN, central carbon metabolism was dysregulated and energy metabolism decreased. After verification, it was found that the levels of NADH, ATP, and reactive oxygen species (ROS) decreased, and superoxide dismutase and catalase activities increased. These findings suggest that inhibition of central carbon and energy metabolic pathways may play an important role in the resistance of S. aureus to gentamicin, and that gentamicin resistance is associated with oxidative stress.Significance: The overuse and misuse of antibiotics have led to bacterial antibiotic resistance, which is a serious threat to human health. Understanding the mechanisms of antibiotic resistance will help better control these antibiotic-resistant pathogens in the future. The present study characterized the differential proteome of gentamicin-resistant Staphylococcus aureus using the most advanced DIA-based proteomics technology. Many of the differential expressed proteins were related to metabolism, specifically, reduced central carbon and energy metabolism. Lower levels of NADH, ROS, and ATP were detected as a consequence of the reduced metabolism. These results reveal that downregulation of protein expression affecting central carbon and energy metabolisms may play an important role in the resistance of S. aureus to gentamicin.

A Novel Strategy to Enhance Antioxidant Content in Saccharomyces Cerevisiae Based on Oxygen Pressure.

Antioxidant foods represent a potent lever to improve diets while creating value. Yet, their cultivation is often tied to a specific area and climate, limiting availability and increasing market cost. Therefore, microorganism-based antioxidant production emerges as a promising technology to solve these problems. In this view, a novel process was investigated for antioxidant accumulation in yeast culture. S. cerevisiae cells were exposed to various hyperbaric air conditions from 1 to 9 bar (A). Yeast cultures exhibited an increased reactive oxygen species content, which induced oxidative defense expression. After a few hours, reactive oxygen species levels decreased while antioxidant contents remained high, leading to a net increase in antioxidant power. At 6 bar (A), yeast achieved the highest net antioxidant power (phenolics content +48.3 ± 18.6 %, reducing power +120 ± 11.4 %) with an acceptable growth rate (0.27 h-1). Regarding time evolution, a 2 h exposure seems to be the optimum: cells have the lowest reactive oxygen species level while their antioxidant power is increased. From a biotechnological perspective, this finding highlights air pressure as an antioxidant-manipulating stress strategy. Moreover, the proposed process led to a patent that could potentially reduce energy and chemical consumption in such antioxidant accumulation processes.

An overlooked influence of reactive oxygen species on ammonia-oxidizing microbial communities in redox-fluctuating aquifers

Reactive oxygen species (ROS) are ubiquitous in O2-perturbed aquifers, but their role in shaping ammonia-oxidizing microbial communities is not clear. This study examined the dynamic responses of ammonia-oxidizing microorganisms (AOMs) in redox-fluctuating aquifers to ROS via field investigation and in-lab verification using transcriptomes/ metatranscriptome and RT-qPCR. Ammonia-oxidizing archaea (AOA) dominated recharge aquifers with lower ROS levels, whereas ammonia-oxidizing bacteria (AOB) and heterotrophic nitrifying aerobic bacteria (HNB) predominated in discharge areas with higher ROS levels. Similar succession in AOM enrichments was found in that the dominant AOMs changed from AOA Nitrosopumilus to AOB Nitrosomonas with increasing ROS. Ammonia oxidation and antioxidant capacity differed significantly among three AOM isolates exposed to ROS. ROS decreased the amoA gene expression of AOA strain Nitrososphaera viennensis PLX03, accompanied by inhibited ammonia oxidation capacity. By contrast, the catalase and superoxide dismutase activities of the AOB strain Nitrosomonas oligotropha PLL12 and HNB strain Pseudomonas aeruginosa PLL01 increased, and the antioxidant genes katG, sodA, ahpC, and ahpF were significantly upregulated. These results demonstrate that ROS exert an important influence on AOMs in redox-fluctuating aquifers. This study improves our understanding of the ecological niches of AOMs in surface/subsurface environments.

Noncoding RNAs Controlling Oxidative Stress in Cancer

Mitochondria in cancer cells tend to overproduce reactive oxygen species (ROS), inducing a vicious cycle between mitochondria, ROS, genomic instability, and cancer development. The first part of this review deals with the role of noncoding RNAs in regulating mitochondrial ROS production and the expression of antioxidants in cancer cells, preventing the increase of ROS in the tumor microenvironment. In addition, cytotoxic T and natural killer cells release high levels of ROS, inducing cell death, while anti-immune regulatory T cells, tumor-associated M2 macrophages, and myeloid-derived suppressor cells, at least at the initial stage of tumor growth, release low levels of ROS supporting tumor growth. Therefore, this review's second part deals with noncoding RNAs' role in regulating the metabolic reprogramming of immune cells about ROS release. Furthermore, the enrichment of noncoding RNAs in microvesicles allows communication between cell types in a tumor and between a tumor and tumor-adjacent tissues. Therefore, the third part illustrates how noncoding RNA-containing microvesicles secreted by mesenchymal stem cells and primary tumor cells may primarily aid the shift of immune cells to a pro-oncogenic phenotype. Conversely, microvesicles released by tumor-adjacent tissues may have the opposite effect. Our review reveals that a specific noncoding RNA may affect oxidative stress by several mechanisms, which may have opposite effects on tumor growth. Furthermore, they may be involved in mechanisms other than regulating oxidative stress, which may level out their effects on oxidative stress and tumor growth. In addition, several noncoding RNAs might share a specific function, making it very unlikely that intervening with only one of these noncoding RNAs will block this particular mechanism. Overall, further validation of the interaction between noncoding RNAs about cancer types and stages of tumor development is warranted.

Positive effects of low-dose photodynamic therapy with aminolevulinic acid or its methyl ester in skin rejuvenation and wound healing: An update.

In dermatology, photodynamic therapy (PDT) is widely used in skin tumors, infections, etc., because of the killing effect triggered by toxic reactive oxygen species (ROS). However, the ROS concentration is determined by various photosensitizer concentrations and formulations, as well as various irradiation parameters. Low-dose PDT leads to sufficiently low ROS level, which results in biological effects that are the exact opposite of the killing potency. Therefore, in recent years, low-dose PDT has been exploited in improving aging and wound. Low-dose ALA/MAL PDT might improve aging through promoting the proliferation of fibroblasts, blocking DNA damage, counteracting oxidative stress, inhibiting melanogenesis, and remodeling lymphatic vessels in aged skin. Promoting fibroblasts and epidermal stem cells proliferation and migration, promoting granulation tissue formation and angiogenesis and regulating the inflammatory process might be the mechanisms of low-dose ALA/MAL PDT in wound healing. Nevertheless, the positive effects of low-dose PDT have not been thoroughly investigated in dermatology, and high-quality studies are still needed to fill the relevant vacancy.