Reduction Of Reactive Oxygen Species Research Articles

Comparative Physiological, Biochemical, and Leaf Proteome Responses of Contrasting Wheat Varieties to Drought Stress.

Drought stress severely affects crop productivity and threatens food security. As current trends of global warming are predicted to exacerbate droughts, developing drought-resilient crops becomes urgent. Here, we used the drought-tolerant (BW35695) and drought-sensitive (BW4074) wheat varieties to investigate the physiological, biochemical, and leaf proteome responses underpinning drought tolerance. In response to drought, the tolerant variety had higher osmolyte accumulation and maintained higher leaf water content than the sensitive variety. BW35695 also had an enhanced antioxidant enzyme capacity and reduced reactive oxygen species (ROS), resulting in diminished membrane lipid damage, as reflected by malondialdehyde content. Proteomic analysis revealed that drought-induced differential expression of proteins involved in diverse biological processes in both wheat varieties, including primary and secondary metabolism, protein synthesis/folding/degradation, defense/ROS detoxification, energy, transcription, and cell structure. Notably, photosynthesis emerged as the most enriched biochemical process targeted for suppression in the drought-tolerant BW35695 wheat, but not in drought-sensitive BW4074, possibly as a survival strategy for averting cell damage inflicted by photosynthesis-derived ROS. Additionally, protein synthesis-related proteins were highly upregulated in BW35695, presumably to drive cell-wide stress-adaptive responses. The protein network identified here will be useful in further studies to understand the molecular basis for divergent drought response phenotypes in crops.

Exploring the Therapeutic Potential of Green Tea (Camellia sinensis L.) in Anti-Aging: A Comprehensive Review of Mechanisms and Findings.

Green tea (GT) is rich in Phyto-active compounds such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), catechin, and tannic acid, which exhibit synergistic effects when combined. Preclinical studies demonstrate that GT and its compounds can reduce reactive oxygen species (ROS), enhance antioxidant capacity, and alleviate aging-related issues such as memory impairments, cognitive decline, and shortened lifespan. Clinical trials corroborate the efficacy of topical GT formulations in improving skin tone, texture, and elasticity and reducing wrinkles. The present manuscript summarizes the recent update on the anti-aging potential of GT and its possible mechanisms. The literature survey suggested that GT consumption is linked to improved cognition, reduced depression levels, and activation of pathways in model organisms like C. elegans. Additionally, tea polyphenols enhance fibroblast mitophagy, boost hippocampal synaptic plasticity in rodents, and mitigate age-related cognitive decline. Moreover, EGCG exhibits anti-aging properties by reducing TNF-induced MMP-1 expression, suppressing ERK signaling, and inhibiting MEK and Src phosphorylation in human dermal fibroblasts. In the context of skin permeation and deposition, optimized transpersonal formulation (TF) incorporating EGCG and hyaluronic acid (HA) demonstrated significantly increased skin permeation and deposition of EGCG compared to plain EGCG. Furthermore, EGCG protects cardiomyocytes via the PPARγ pathway and combats age-related muscle loss through miRNA-486-5p regulation, AKT activation, and FoxO1a-mediated expression of MuRF1 and Atrogin-1. In conclusion, the regular consumption of GT holds promise for promoting physical and mental health, delaying brain and skin aging, and improving overall health by enhancing total antioxidant capacity.

Mechanistic studies on the alleviation of lipid accumulation and oxidative stress by Majia pomelo seed oil

In this study, hot-pressed Majia pomelo seed oil (MPSO), which has high oxidative stability and antioxidant capacity, was used to study the effects and potential mechanisms of lipid accumulation and oxidative stress. The results indicated that the low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) levels in HepG2 cells were lowest when the MPSO concentration was 0.5 mg/mL. At this concentration, MPSO could alleviate oleic acid (OA)-induced lipid accumulation, reduce intracellular lipid level, and decrease lipid and cholesterol synthesis by increasing AMPK phosphorylation and down-regulating the expression levels of genes and proteins of ACC, SREBP-1c, PPAR-γ, and FAS. Meanwhile, MPSO can reduce reactive oxygen species (ROS) and malondialdehyde (MDA) content and enhance superoxide dismutase (SOD) content in HepG2 cells by down-regulating the expression levels of Nrf2, γ-GCS, and HO-1 genes and proteins, thus acting as an anti-oxidative stress. In addition, molecular docking results indicated that the active ingredients of MPSO could effectively bind AMPK protein and Keap1 protein, which further demonstrated that MPSO could alleviate lipid accumulation and oxidative stress.

Integrated transcriptomic and proteomic analysis revealed the regulatory role of 5-azacytidine in kenaf salt stress alleviation

Salinity stress limits agricultural production. The DNA methyltransferase inhibitor, 5-azacitidine (5-azaC), plays a role in plant abiotic stress regulation, but its molecular basis in mediating salinity tolerance in kenaf remains unclear. To investigate the effects on 5-azaC on alleviating salt stress, kenaf seedlings were pre-treated with 0, 50, 100, 150, and 200 μM 5-azaC and then exposed to 150 mM NaCl in a nutrient solution. Physiological, transcriptomic, and proteomic analyses were conducted on the root system to understand the regulatory mechanism of 5-azaC (comparing 5-azaC150 and control group 5-azaC0) under salt stress. The results indicated that 5-azaC significantly mitigated salt stress in kenaf by activating the antioxidant system, reducing reactive oxygen species (ROS), and increasing starch, soluble sugars, and adenosine triphosphate (ATP) content. A total of 14,348 differentially expressed genes (DEGs) and 313 differentially abundant proteins (DAPs) were identified. Combined proteomic and transcriptomic analysis revealed 27 DEGs/DAPs, with jointly up-regulated proteins (genes) including HcTHI1, HcBGLU11, and HcCBL1, and jointly down-regulated proteins (genes) including HcGAPDH, HcSS, and HcPP2C52. Overexpression and virus-induced gene silencing (VIGS) of HcPP2C52 demonstrated its role as a negative regulator of salt tolerance. These findings provide insights into the regulatory role of 5-azaC in plant responses to abiotic stresses. SignificanceThe specific molecular mechanism by which 5-azaC affects gene expression and protein activity of kenaf has been revealed, leading to enhanced salt tolerance.

Neutrophils with low production of reactive oxygen species are activated during immune priming and promote development of arthritis

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease mediated by immune cell dysfunction for which there is no universally effective prevention and treatment strategy. As primary effector cells, neutrophils are important in the inflammatory joint attack during the development of RA. Here, we used single-cell sequencing technology to thoroughly analyze the phenotypic characteristics of bone marrow-derived neutrophils in type II collagen (COL2)-induced arthritis (CIA) models, including mice primed and boosted with COL2. We identified a subpopulation of neutrophils with high expression of neutrophil cytoplasmic factor 1 (NCF1) in primed mice, accompanied by a characteristic reactive oxygen species (ROS) response, and a decrease in Ncf1 expression in boosted mice with the onset of arthritis. Furthermore, we found that after ROS reduction, arthritis occurred in primed mice but was attenuated in boosted mice. This bidirectional effect of ROS suggested a protective role of ROS during immune priming. Mechanistically, we combined functional assays and metabolomics identifying Ncf1-deficient neutrophils with enhanced migration, chemotactic receptor CXCR2 expression, inflammatory cytokine secretion, and Th1/Th17 differentiation. This alteration was mainly due to the metabolic reprogramming of Ncf1-deficient neutrophils from an energy supply pathway dominated by gluconeogenesis to an inflammatory immune pathway associated with the metabolism of histidine, glycine, serine, and threonine signaling, which in turn induced arthritis. In conclusion, we have systematically identified the functional and inflammatory phenotypic characteristics of neutrophils under ROS regulation, which provides a theoretical basis for understanding the pathogenesis of RA, to further improve prevention strategies and identify novel therapeutic targets.

Harnessing Cannabis sativa Oil for Enhanced Skin Wound Healing: The Role of Reactive Oxygen Species Regulation.

Cannabis sativa emerges as a noteworthy candidate for its medicinal potential, particularly in wound healing. This review article explores the efficacy of cannabis oil in reducing reactive oxygen species (ROS) during the healing of acute and chronic wounds, comparing it to the standard treatments. ROS, produced from various internal and external sources, play a crucial role in wound development by causing cell and tissue damage. Understanding the role of ROS on skin wounds is essential, as they act both as signaling molecules and contributors to oxidative damage. Cannabis oil, recognized for its antioxidant properties, may help mitigate oxidative damage by scavenging ROS and upregulating antioxidative mechanisms, potentially enhancing wound healing. This review emphasizes ongoing research and the future potential of cannabis oil in dermatological treatments, highlighted through clinical studies and patent updates. Despite its promising benefits, optimizing cannabis oil formulations for therapeutic applications remains a challenge, underscoring the need for further research to realize its medicinal capabilities in wounds.

Anti-inflammatory effects of 1,7-dihydroxy-3,4-dimethoxyxanthone through inhibition of M1-phenotype macrophages via arginine/mitochondrial axis.

It is known that 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN), derived from Securidaca inappendiculata Hassk., exhibits anti-inflammatory and analgesic activities and inhibits M1 polarization of macrophages. However, its ability to alleviate inflammation induced by pro-inflammatory cytokines in THP-1 cells and its anti-inflammatory mechanisms remain unclear. THP-1 cells were treated with phorbol 12-myristate-13-acetate to differentiate and divided into three groups. They were stimulated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). The toxicity of XAN was assessed using Cell Counting Kit-8, and the expression of various genes and proteins was analyzed using real-time quantitative polymerase chain reaction, flow cytometry, and western blotting. Transmission electron microscopy was used to observe changes in mitochondrial structure. XAN at concentrations ≤ 10µg/mL did not affect THP-1 cell viability and reduced the mRNA expression of pro-inflammatory factors, including interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), NOD-like receptor thermal protein domain protein 3 (NLRP3), and tumor necrosis factor-α (TNF-α). XAN also increased the levels of anti-inflammatory factors, including chemokine ligand 22, mannose receptor (CD206), IL-10, peroxisome proliferator-activated receptor-γ, and transglutaminase 2. Additionally, XAN downregulated the expression of inflammation-related proteins iNOS, NLRP3, and IL-1β; significantly increased the expression of arginase 1, ornithine decarboxylase, and arginine metabolism-related proteins and genes; inhibited mitochondrial damage; and reduced reactive oxygen species (ROS) generation. XAN enhanced the arginine metabolism pathway, prevented mitochondrial damage, reduced ROS levels, and provided an effective defensive response against LPS/IFN-γ-induced inflammation.

Inhibition of calpain reduces oxidative stress and attenuates pyroptosis and ferroptosis in Clostridium perfringens Beta-1 toxin-induced macrophages

Clostridium perfringens Beta-1 toxin (CPB1) is a lethal toxin, which can lead to necrotic enteritis, but the pathological mechanism has not been elucidated. We investigated whether reactive oxygen species (ROS) participated in CPB1-induced pyroptosis and ferroptosis, and investigated the effects of calpain on CPB1-induced oxidative stress and inflammation. Scavenging ROS by N-acetyl cysteine (NAC) led to the reduction of ROS, inhibited the death of macrophages, cytoplasmic swelling and membrane rupture, the expression of pyroptosis-related proteins and proinflammatory factor, while increased the expression of anti-inflammatory factors in cells treated with rCPB1. Adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1 (ATP5A1) was identified specifically interact with rCPB1. Silencing ATP5A1 inhibited accumulation of ATP and ROS, leaded to less cytoplasmic swelling and membrane rupture, attenuated pyroptosis and inflammation in rCPB1-treated cells. We also found that rCPB1 induces ferroptosis in macrophages, and the level of ferroptosis was similar with H2O2. Of note, H2O2 is a major ROS source, indicated that ROS production may play a major role in the regulation of ferroptosis in macrophages treated with rCPB1. This finding was further corroborated in rCPB1- induced human acute monocytic leukemia cells, which were treated with NAC. In addition, the inhibition of ferroptosis using liproxstatin-1 inhibited the shriveled mitochondrial morphology, increased the expression of glutathione peroxidase 4, nicotinamide adenine dinucleotide (phosphate) hydrogen: quinone oxidoreductase 1 and cysteine/glutamic acid reverse transport solute carrier family 7 members 11, decreased the expression of heme oxygenase 1, nuclear receptor coactivator 4 and transferrin receptor proteins, reduced malondialdehyde and lipid peroxidation levels, and increased intracellular L-glutathione levels in cells treated with rCPB1. Furthermore, calpain inhibitor PD151746 was used to investigate how pyroptosis and ferroptosis were involved simultaneously in rCPB1-treated macrophages. We showed that PD151746 inhibited ATP and ROS production, reversed the representative pyroptosis/ferroptosis indicators and subsequently reduced inflammation. The above findings indicate that rCPB1 might lead to macrophage pyroptosis and ferroptosis through the large and sustained increase in intracellular calpain and oxidative stress, further lead to inflammation.

Ginkgo Flavone Aglycone Ameliorates Atherosclerosis via Inhibiting Endothelial Pyroptosis by Activating the Nrf2 Pathway.

Natural antioxidants have been shown to be effective against atherosclerosis. Ginkgo flavone aglycone (GA) has strong antioxidant properties and can protect against endothelial damage. However, the mechanisms by which GA protects against atherosclerosis remain largely unexplored. This study hopes to find the anti-atherosclerotic mechanism of GA. ApoE-/- mice fed a high-fat diet were used for modeling atherosclerosis. The efficacy of GA on mice with atherosclerosis was evaluated based on the following indicators: Oil Red O staining, Masson staining, lipid content, and apoptosis. Transmission electron microscopy, Western blot, immunofluorescence staining, and propidium iodide staining were used to analyze the effects of GA on ox-LDL-treated human aortic endothelial cells. GA activated Nrf2 by promoting the nuclear translocation of Nrf2, thereby inhibiting endothelial pyroptosis. GA prevented endothelial pyroptosis suppressed oxidative stress, and inhibited the development of atherosclerosis in ApoE-/- mice fed high-fat diets. At the cellular level, GA suppressed ox-LDL-induced pyroptosis of HAECs by reducing reactive oxygen species (ROS) levels and inhibiting NLRP3 inflammasome. Furthermore, siRNA targeting Nrf2 or ML385, an Nrf2 inhibitor, reversed these effects. GA liberated Nrf2 from Keap1 sequestration, enhanced the nuclear translocation of Nrf2 and the transcription of downstream antioxidant proteins, reinforced the antioxidant defense system, and inhibited oxidative stress, thereby preventing endothelial cell pyroptosis, and attenuating the progression of atherosclerosis. This study indicated that GA mitigated endothelial pyroptosis by modulating Keap1/Nrf2 interactions, shedding light on the potential mechanisms underlying the protective effects of natural antioxidants against atherosclerosis.

ATH434, a promising iron-targeting compound for treating iron regulation disorders.

Cytotoxic accumulation of loosely bound mitochondrial Fe2+ is a hallmark of Friedreich's Ataxia (FA), a rare and fatal neuromuscular disorder with limited therapeutic options. There are no clinically approved medications targeting excess Fe2+ associated with FA or the neurological disorders Parkinson's disease and Multiple System Atrophy. Traditional iron-chelating drugs clinically approved for systemic iron overload that target ferritin-stored Fe3+ for urinary excretion demonstrated limited efficacy in FA and exacerbated ataxia. Poor treatment outcomes reflect inadequate binding to excess toxic Fe2+ or exceptionally high affinities (i.e. ≤10-31) for non-pathologic Fe3+ that disrupts intrinsic iron homeostasis. To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 and DFX had moderate Fe2+ binding affinities (Kd's of 1-4 µM), similar to endogenous iron chaperones, while the remaining had weaker divalent metal interactions. These compounds had low/moderate affinities for Fe3+(0.46-9.59µM) relative to DFX and DFP. While all compounds coordinated iron using molecular oxygen and/or nitrogen ligands, thermodynamic analyses suggest ATH434 completes Fe2+ coordination using H2O. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores.

Senescence Rejuvenation through Reduction in Mitochondrial Reactive Oxygen Species Generation by Polygonum cuspidatum Extract: In Vitro Evidence.

Oxidative stress caused by reactive oxygen species (ROS) is one of the major causes of senescence. Strategies to reduce ROS are known to be important factors in reversing senescence, but effective strategies have not been found. In this study, we screened substances commonly used as cosmetic additives to find substances with antioxidant effects. Polygonum cuspidatum (P. cuspidatum) extract significantly reduced ROS levels in senescent cells. A novel mechanism was discovered in which P. cuspidatum extract reduced ROS, a byproduct of inefficient oxidative phosphorylation (OXPHOS), by increasing OXPHOS efficiency. The reduction in ROS by P. cuspidatum extract restored senescence-associated phenotypes and enhanced skin protection. Then, we identified polydatin as the active ingredient of P. cuspidatum extract that exhibited antioxidant effects. Polydatin, which contains stilbenoid polyphenols that act as singlet oxygen scavengers through redox reactions, increased OXPHOS efficiency and subsequently restored senescence-associated phenotypes. In summary, our data confirmed the effects of P. cuspidatum extract on senescence rejuvenation and skin protection through ROS reduction. This novel finding may be used as a treatment in senescence rejuvenation in clinical and cosmetic fields.

The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in aging.

Aging is closely associated with various cerebrovascular pathologies that significantly impact brain function, with cerebral small vessel disease (CSVD) being a major contributor to cognitive decline in the elderly. Consequences of CSVD include cerebral microhemorrhages (CMH), which are small intracerebral bleeds resulting from the rupture of microvessels. CMHs are prevalent in aging populations, affecting approximately 50% of individuals over 80, and are linked to increased risks of vascular cognitive impairment and dementia (VCID). Hypertension is a primary risk factor for CMHs. Vascular smooth muscle cells (VSMCs) adapt to hypertension by undergoing hypertrophy and producing extracellular matrix (ECM) components, which reinforce vessel walls. Myogenic autoregulation, which involves pressure-induced constriction, helps prevent excessive pressure from damaging the vulnerable microvasculature. However, aging impairs these adaptive mechanisms, weakening vessel walls and increasing susceptibility to damage. Insulin-like Growth Factor 1 (IGF-1) is crucial for vascular health, promoting VSMC hypertrophy, ECM production, and maintaining normal myogenic protection. IGF-1 also prevents microvascular senescence, reduces reactive oxygen species (ROS) production, and regulates matrix metalloproteinase (MMP) activity, which is vital for ECM remodeling and stabilization. IGF-1 deficiency, common in aging, compromises these protective mechanisms, increasing the risk of CMHs. This review explores the vasoprotective role of IGF-1 signaling in the cerebral microcirculation and its implications for preventing hypertension-induced CMHs in aging. Understanding and addressing the decline in IGF-1 signaling with age are crucial for maintaining cerebrovascular health and preventing hypertension-related vascular injuries in the aging population.

Oligoprotective Activity of Levetiracetam Against Glutamate Toxicity: An in vitro Study.

The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures. Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes. At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 μM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting. LEV at 1-800 μM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 μM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 μM) against glutamate toxicity was accompanied by reduced Reactive Oxygen Species (ROS) accumulation and Malondialdehyde (MDA) level. Moreover, 100 μM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure. Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.

Biofilm-camouflaged Prussian blue synergistic mitochondrial mass enhancement for Alzheimer's disease based on Cu2+ chelation and photothermal therapy

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive and memory impairment. Metal ion imbalance and Mitochondrial dysfunction, leading to abnormal aggregation of β-amyloid protein (Aβ), are key factors in the pathogenesis of AD. Therefore, we designed a composite nanometer system of red blood cell (RBC) membranes-encapsulated Prussian blue nanoparticles (PB/RBC). Prussian blue nanoparticles (PBNPs) can chelate Cu2+ and reduce reactive oxygen species (ROS). The RBC membranes are a kind of natural long-lasting circulating carrier. At the same time, through NIR irradiation, the excellent photothermal ability of PBNPs can also temporarily open the blood-brain barrier (BBB), enhance the transmission efficiency of PB/RBC across the BBB, and depolymerize the formed Aβ deposits, thereby achieving the optimal therapeutic effect. In vitro and in vivo studies demonstrated that PB/RBC could inhibit Cu2+-induced Aβ monomers aggregation, eliminate the deposition of Aβ plaques, improve the quality of mitochondria, restore the phagocytic function of microglia, alleviate neuroinflammation in APP/PS1 mice, and repair memory damage. In conclusion, our biofilm-camouflaged nano-delivery system provides significant neuroprotection by inhibiting Cu2+-induced Aβ monomers aggregation, photothermally depolymerizing Aβ fibrils and reducing the level of ROS, thus effectively ameliorating and treating AD.

Melatonin mitigates matrix stiffness-induced intervertebral disk degeneration by inhibiting reactive oxygen species and melatonin receptors mediated PI3K/AKT/NF-κB pathway.

Intervertebral disk degeneration (IVDD) may lead to an increase in extracellular matrix (ECM) stiffness, potentially contributing to the progression of the disease. Melatonin reportedly mitigates IVDD; however, its potential to attenuate elevated matrix stiffness-induced IVDD remains unexplored. Therefore, we aimed to investigate whether melatonin can alleviate the progression of IVDD triggered by increased matrix stiffness and elucidate its underlying mechanisms. Nucleus pulposus (NP) tissues were collected from patients, and ECM stiffness, reactive oxygen species (ROS) levels, apoptosis rates, and P65 expression in these tissues with varying Pfirrmann scores were determined. In vitro experiments were conducted to investigate the effects of melatonin on various pathophysiological mechanisms within the NP cells cultured on soft substrates with differing stiffness levels. Our findings revealed a positive correlation between ECM stiffness in human NP tissue and degree of IVDD. In addition, phosphorylation of P65 exhibited a strong association with matrix stiffness. Enhanced levels of ROS and cellular apoptosis were observed within degenerated intervertebral disks. In vitro experiments demonstrated that melatonin significantly inhibited catabolism and apoptosis induced by stiff matrices, along with elevated ROS levels. Furthermore, we observed that melatonin inhibited NP cell catabolism and apoptosis by reducing the melatonin receptors mediated activation of the PI3K/AKT and nuclear factor-kappa B (NF-κB) pathways. Also, we found that the reduction of ROS by melatonin can assist in inhibiting the activation of the NF-κB pathway. The outcomes of the in vivo experiments corroborated the results of the in vitro experiments, illustrating that melatonin treatment could alleviate the compression-induced upregulation of matrix stiffness in NP and IVDD. Collectively, melatonin can potentially alleviate high matrix stiffness-induced IVDD by reducing intracellular ROS levels and inhibiting the PI3K/AKT/NF-κB pathway.NEW & NOTEWORTHY Melatonin mitigates intervertebral disk degeneration (IVDD) induced by matrix stiffness through reactive oxygen species (ROS) reduction. Matrix stiffness is related to increased nucleus pulposus cell ROS, apoptosis, and degeneration. Melatonin inhibits PI3K/AKT/NF-κB pathways via melatonin receptors in a stiff matrix environment. In vivo, melatonin restores disk height and alleviates IVDD progression.

N-acetylcysteine promotes doxycycline resistance in the bacterial pathogen Edwardsiella tarda

ABSTRACT Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on Edwardsiella tarda ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of E. tarda to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in E. tarda, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying E. tarda resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.

Evaluation of glycyrrhetinic acid in attenuating adverse effects of a high-fat diet in largemouth bass (Micropterus salmoides)

Glycyrrhetinic acid (GA) has been shown to promote growth characteristics and play a crucial role in anti-inflammatory responses in animals. To investigate the effects of dietary GA supplementation on growth performance, intestinal inflammation, and intestinal barrier protection in largemouth bass (Micropterus salmoides) fed a high-fat diet (HFD), a 77-day feeding experiment was conducted. A total of 750 largemouth bass, initially averaging 17.39 ± 0.09 g in body weight, were randomly allocated to five experimental groups and fed a control diet, a HFD, and the HFD diet supplemented with GA at either 0.5, 1.0, or 1.5 mg/kg, named as control, HDF, HFD+GA 0.5, HFD+GA 1.0, and 1.5 HFD+GA 1.5, respectively. Each group contained three replicates. The study revealed that dietary GA improved final body weight (P < 0.001), percent weight gain (P = 0.041), and feed intake (P < 0.001), all of which had been affected by a HFD in largemouth bass (P < 0.05). Supplementation of HFD with 1.0 mg/kg GA increased the mRNA expressions and protein levels of corresponding tight junctions, occludin, zonula occluden-1 (ZO-1) and claudin-1 in the intestines of largemouth bass. Furthermore, the addition of HFD with both of 0.5 and 1.0 mg/kg GA decreased the mRNA expressions of pro-inflammatory genes such as interleukin-1β (IL-1β), IL-18, and cysteinyl aspartate specific proteinase 1 (caspase-1), as well as proteins associated with pyroptosis-induced inflammation, including NOD-like receptor family and pyrin domain contain 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), gasdermin E (GSDME), and N-terminal domain of GSDME (GSDME-N) (P < 0.05). Finally, dietary GA supplementation alleviated mitochondrial damage and reduced reactive oxygen species (ROS) production induced by the HFD. It is concluded that GA supplementation in HFD enhances growth performance, increases mRNA expression and protein levels of tight junction-related parameters, decreases mRNA expression and protein levels of pyroptosis-related genes, and alleviates intestinal mitochondrial injury and inflammation induced by HFD.

Lactiplantibacillus plantarum ZJ316 alleviates the oxidative stress and cellular apoptosis via modulating Nrf2/HO-1 signaling pathway

Oxidative stress is vital in gastrointestinal diseases, but how lactic acid bacteria protect human gastric adenocarcinoma cells (AGS) is unclear. Here, we aimed to investigate Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) for its potential to alleviate oxidative stress in AGS cells and elucidate mechanisms involved. Treatment with L. plantarum ZJ316 and fermentation supernatant (ZJ316 FS) bolstered cell viability under hydrogen peroxide (H2O2)-induced oxidative stress, boosting antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) while reducing reactive oxygen species (ROS) and malondialdehyde (MDA). Oral probiotics also alleviated oxidative damage from D-galactose in mice. Additionally, L. plantarum ZJ316 and ZJ316 FS alleviated H2O2-induced inflammation and apoptosis by modulating the expression of inflammatory and apoptotic factors. However, the protective effect was hindered when pretreated with the Nrf2 inhibitor ML385. These findings suggest that L. plantarum ZJ316 and fermentation supernatant alleviate oxidative damage by activating the Nrf2/HO-1 pathway, showing promise in development of antioxidant functional foods.

Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway

BackgroundAging-induced decline in ciliary muscle function is an important factor in visual accommodative deficits in elderly adults. With this study, we provide an innovative investigation of the interaction between ciliary muscle aging and oxidative stress. MethodsTricolor guinea pigs were used for the experiments in vivo and primary guinea pig ciliary smooth muscle cells were used for the experiments in vitro. ResultsWe enriched for genes associated with muscle-aging-lutein relationship using bioinformatics, including Nuclear factor-erythroid 2-related factor-2 (Nrf2), Glutathione Peroxidase (GPx) gene family, Superoxide Dismutase (SOD) gene family, NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Heme Oxygenase-1 (HO-1). After gavage to aged guinea pigs, lutein reduced Reactive Oxygen Species (ROS) and P21 levels in senescent ciliary muscle; lutein decreased refractive error and restored accommodation of the eye. In addition, lutein increased GPx, SOD, and Catalase (CAT) levels in serum; lutein increased GPx and CAT levels in ciliary bodies. Lutein regulated the expression of proteins such as Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and downstream proteins in senescent ciliary bodies. Similarly, guinea pig ciliary muscle cell senescence was associated with oxidative stress. In vitro, 100 μM lutein reversed the damage caused by 800 μM H2O2; it reduced Senescence-Associated β-galactosidase (SA-β-Gal) and ROS activites, cell apoptosis and cell migration. Also, lutein increased the expression of smooth muscle contractile proteins. Lutein also increased the expression of Nrf2, GPx2, NQO1 and HO-1, decreased the expression of Keap1. A reduction in Nrf2 activity led to a reduction in the ability of lutein to activate antioxidant enzymes in the cells, thus reducing its inhibitory effect on cell senescence. Conclusionlutein improved resistance to oxidative stress in senescent ciliary muscle in vivo and in vitro by regulating the Keap1/Nrf2/Antioxidant Response Element pathway. We have innovatively demonstrated the molecular pharmacological mechanism by which lutein reverse age-related ciliary muscle systolic and diastolic deficits.

Mitigating Cold Ischemic Injury: HTK, UW and IGL-2 Solution's Role in Enhancing Antioxidant Defence and Reducing Inflammation in Steatotic Livers.

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.