Redox State Of Cells Research Articles

Protective properties of the edible halophyte Carpobrotus edulis (L.) N.E.Br. towards neoformed food contaminants-related oxidative stress and genotoxicity

Carpobrotus edulis (L.) N.E.Br. is an edible halophyte native to South Africa, where it has been traditionally consumed as food, revealing its nutritional value, and used in the treatment of human diseases probably due to the accumulation of bioactive compounds such as polyphenols. These compounds have potential to display valuable biological activities that could bring several benefits to the human being, including the mitigation of toxicity induced by food contaminants. Therefore, this study investigated biological activities with health-promoting potential of a C. edulis ethanol extract (CEE), such as antioxidant, antigenotoxic, and antimutagenic. CEE was shown by LC-DAD-ESI/MSn to be composed of 16 polyphenols. The extract exhibited antioxidant properties by protecting Saccharomyces cerevisiae viability and improving the redox state of HepG2 cells under oxidative stress. Antigenotoxicity of CEE against H2O2-induced oxidative damage was detected in HepG2 and Caco-2 cells by comet assay and subsequently observed in the dominant deletion assay in S. cerevisiae. Antigenotoxicity and antimutagenicity of CEE towards the neoformed contaminant benzo[a]pyrene was found in HepG2 and Caco-2 cells by comet assay and in Salmonella typhimurium using the Ames test, respectively. The disclosed antigenotoxic and antimutagenic properties of C. edulis further advance its potential for application in food and nutraceutical industries for health benefits.

Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition.

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped with neutrophil membranes and surface modified with the N,N-dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga). In the AP mouse model, the formulation exhibited efficient recruitment at the inflammatory endothelium, trans-endothelial migration, and precise acinar cell targeting, resulting in rapid pancreatic localization and higher accumulation. A single low dose of the formulation (BA: 200 μg kg-1, Ga: 0.75 mg kg-1) significantly reduced pancreas function indicators to close to normal levels at 24 h, effectively restored the cell redox status, reduced apoptotic cell proportion, and blocked the systemic inflammatory amplified cascade, resulting in a dramatic increase in the survival rate from 58.3 to even 100%. Mechanistically, the formulation inhibited endoplasmic reticulum stress (IRE1/XBP1 and ATF4/CHOP axis) and restored impaired autophagy (Beclin-1/p62/LC3 axis), thereby preserving dying acinar cells and restoring the cellular "health status". This formulation provides an upstream therapeutic strategy with clinical translation prospects for AP management through synergistic ion homeostasis regulation and pancreatic autodigestion inhibition.

Gallic acid mitigates intestinal inflammation and loss of tight junction protein expression using a 2D-Caco-2 and RAW 264.7 co-culture model

A 2D-intestinal epithelial Caco-2/RAW 264.7 macrophage co-culture model was developed to demonstrate the relative efficacy of different phenolic acids to mitigate changes in Caco-2 epithelial cell redox state initiated both directly by autoxidation products, H2O2, and indirectly through cell communication events originating from cytokine stimulated macrophage. An inducer cocktail (lipopolysaccharide + interferon gamma) was used to activate RAW 264.7 cells in the 2D- Caco-2/RAW co-culture and intracellular changes in Caco-2 cell redox signaling occurred in response to positive changes (p < 0.05) in inflammatory biomarkers derived in macrophage that included IL-6, TNF-α, nitric oxide and peroxynitrite, respectively. Phenolic acids varied in relative capacity to reduce NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) in cocktail inflamed induced macrophage. This response in addition to the relative predisposition of gallic acid (GA) to undergo autoxidation to generate H2O2 activity (p < 0.05), culminated in downstream cell signaling in Caco-2 nuclear factor erythroid 2-related factor (Nrf2) activity (increase 26.9 %), altered monolayer integrity (increase 33.7 %), and release of interleukin 8 (IL-8) (decrease 80.5 %) (p < 0.05). It can be concluded that the co-culture model described herein was useful to assess the importance of communication between cytokine stimulated macrophage and intestinal cells. Moreover, the relative unique efficacy of GA, compared to other phenolic acids tested to protect against activated macrophage induced changes related to intestinal dysfunction were particularly relevant to epithelial redox signaling, intestinal permeability and regulation of tight junction proteins. This study concludes that phenolic acids are not equal in the capacity to protect against intestinal cell dysfunction despite some indication of biological activity.

A Physiological Approach to Explore How Thioredoxin-Glutathione Reductase (TGR) and Peroxiredoxin (Prx) Eliminate H2O2 in Cysticerci of Taenia.

Peroxiredoxins (Prxs) and glutathione peroxidases (GPxs) are the main enzymes of the thiol-dependent antioxidant systems responsible for reducing the H2O2 produced via aerobic metabolism or parasitic organisms by the host organism. These antioxidant systems maintain a proper redox state in cells. The cysticerci of Taenia crassiceps tolerate millimolar concentrations of this oxidant. To understand the role played by Prxs in this cestode, two genes for Prxs, identified in the genome of Taenia solium (TsPrx1 and TsPrx3), were cloned. The sequence of the proteins suggests that both isoforms belong to the class of typical Prxs 2-Cys. In addition, TsPrx3 harbors a mitochondrial localization signal peptide and two motifs (-GGLG- and -YP-) associated with overoxidation. Our kinetic characterization assigns them as thioredoxin peroxidases (TPxs). While TsPrx1 and TsPrx3 exhibit the same catalytic efficiency, thioredoxin-glutathione reductase from T. crassiceps (TcTGR) was five and eight times higher. Additionally, the latter demonstrated a lower affinity (>30-fold) for H2O2 in comparison with TsPrx1 and TsPrx3. The TcTGR contains a Sec residue in its C-terminal, which confers additional peroxidase activity. The aforementioned aspect implies that TsPrx1 and TsPrx3 are catalytically active at low H2O2 concentrations, and the TcTGR acts at high H2O2 concentrations. These results may explain why the T. crassiceps cysticerci can tolerate high H2O2 concentrations.

The redox-sensitive R-loop of the carbon control protein SbtB contributes to the regulation of the cyanobacterial CCM

SbtB is a PII-like protein that regulates the carbon-concentrating mechanism (CCM) in cyanobacteria. SbtB proteins can bind many adenyl nucleotides and possess a characteristic C-terminal redox sensitive loop (R-loop) that forms a disulfide bridge in response to the diurnal state of the cell. SbtBs also possess an ATPase/ADPase activity that is modulated by the redox-state of the R-loop. To investigate the R-loop in the cyanobacterium Synechocystis sp. PCC 6803, site-specific mutants, unable to form the hairpin and permanently in the reduced state, and a R-loop truncation mutant, were characterized under different inorganic carbon (Ci) and light regimes. Growth under diurnal rhythm showed a role of the R-loop as sensor for acclimation to changing light conditions. The redox-state of the R-loop was found to impact the binding of the adenyl-nucleotides to SbtB, its membrane association and thereby the CCM regulation, while these phenotypes disappeared after truncation of the R-loop. Collectively, our data imply that the redox-sensitive R-loop provides an additional regulatory layer to SbtB, linking the CO2-related signaling activity of SbtB with the redox state of cells, mainly reporting the actual light conditions. This regulation not only coordinates CCM activity in the diurnal rhythm but also affects the primary carbon metabolism.

Molecular characterization, cytoprotective, DNA protective, and immunological assessment of peroxiredoxin-1 (Prdx1) from yellowtail clownfish (Amphiprion clarkii)

Peroxiredoxin-1 (Prdx1) is a thiol-specific antioxidant enzyme that detoxifies reactive oxygen species (ROS) and regulates the redox status of cells. In this study, the Prdx1 cDNA sequence was isolated from the pre-established Amphiprion clarkii (A. clarkii) (AcPrdx1) transcriptome database and characterized structurally and functionally. The AcPrdx1 coding sequence comprises 597 bp and encodes 198 amino acids with a molecular weight of 22.1 kDa and a predicted theoretical isoelectric point of 6.3. AcPrdx1 is localized and functionally available in the cytoplasm and nucleus of cells. The TXN domain of AcPrdx1 comprises two peroxiredoxin signature VCP motifs, which contain catalytic peroxidatic (Cp-C52) and resolving cysteine (CR-C173) residues. The constructed phylogenetic tree and sequence alignment revealed that AcPrdx1 is evolutionarily conserved, and its most closely related counterpart is Amphiprion ocellaris. Under normal physiological conditions, AcPrdx1 was ubiquitously detected in all tissues examined, with the most robust expression in the spleen. Furthermore, AcPrdx1 transcripts were significantly upregulated in the spleen, head kidney, and blood after immune stimulation by polyinosinic:polycytidylic acid (poly (I:C)), lipopolysaccharide (LPS), and Vibrio harveyi injection. Recombinant AcPrdx1 (rAcPrdx1) demonstrated antioxidant and DNA protective properties in a concentration-dependent manner, as evidenced by insulin disulfide reduction, peroxidase activity, and metal-catalyzed oxidation (MCO) assays, whereas cells transfected with pcDNA3.1(+)/AcPrdx1 showed significant cytoprotective function under oxidative and nitrosative stress. Overexpression of AcPrdx1 in fathead minnow (FHM) cells led to a lower viral copy number following viral hemorrhagic septicemia virus (VHSV) infection, along with upregulation of several antiviral genes. Collectively, this study provides insights into the function of AcPrdx1 in defense against oxidative stressors and its role in the immune response against pathogenic infections in A. clarkii.

A Meta-analysis of Transcriptome Data to Investigate the Effect of Soy Isoflavones on Breast Cancer Cell.

Breast cancer ranks as the second highest cause of cancer-linked deaths in women, with varying rates between Western and Asian countries. The consumption of phytoestrogens can influence breast cancer occurrence. To comprehend how soy isoflavones impact breast cancer cells, we conducted a meta-analysis, combining gene expression data from multiple studies. This approach aimed to identify crucial transcriptional characteristics driving breast cancer cell response to soy phytoestrogens. The gene expression profiles obtained from the Gene Expression Omnibus and Array Express and were grouped into control and isoflavones exposure conditions. We performed a meta-analysis based on the effect size combination method to identify the differentially expressed genes (DEGs). In addition, we performed Gene Ontology (GO) enrichment analysis, pathway analysis, weighted gene co-expression network analysis (WGCNA) and recursive support vector machine (R-SVM) algorithm. Based on this meta-analysis, we identified 3,890 DEGs, of which 2,173 were up-regulated and 1,717 were down-regulated. For example, SGCG, PLK2, and TBC1D9 were the most highly down-regulated genes and EGR3, WISP2, and FKBP4 were the most highly expressed genes in the isoflavones exposure condition. The functional enrichment and pathway analysis were revealed "cell division" and "cell cycle" among the most enriched terms. Among the identified DEGs, 269 transcription factor (TF) genes belonged to 42 TF families, where the C2H2 ZF, bZIP, and bHLH were the most prominent families. We also employed the R-SVM for detecting the most important genes to classify samples into isoflavones exposure and control conditions. It identified a subset of 100 DEGs related to regulation of cell growth, response to estradiol, and intermediate ribonucleoside monophosphate in the purine (IMP) metabolic process. Moreover, the WGCNA separated the DEGs into five discrete modules strongly enriched for genes involved in cell division, DNA replication, embryonic digit morphogenesis, and cell-cell adhesion. Our analysis provides evidence suggesting that isoflavone affects various mechanisms in cells, including pathways associated with NF-κB, Akt, MAPK, Wnt, Notch, p53, and AR pathways, which can lead to the induction of apoptosis, the alteration of the cell cycle, the inhibition of angiogenesis, and interference in the redox state of cells. These findings can shed light on the molecular mechanisms that underlie the response of breast cancer cells to isoflavones.

Mitigation of lead toxicity in Brassica juncea L. by sulphur application – Via various biochemical and transcriptomic strategies

The present study was designed to elucidate whether exogenously applied sulphur (S) (S1; 100 ppm, S2; 200 ppm S) alleviate lead (Pb)-induced (Pb1; 100 ppm, Pb2; 200 ppm and Pb3; 300 ppm Pb) stress in the leaves of Brassica juncea. To study this effect, oxidative stress biomarkers (hydrogen peroxide and malondialdehyde), enzymatic antioxidants (ascorbate peroxidase (APX), glutathione reductase (GR)), non-enzymatic antioxidants (chlorophyll and carotenoids) and S-metabolic enzymes like adenosine triphosphate sulfurylase (ATPS), O-acetylserine(thiol)lyase (OASTL) were studied. Pb treatment dramatically inhibited plant development by increasing lipid peroxidation and hydrogen peroxide (H2O2) accumulation by 34.82 and 238.89 % respectively at 90 days plant. The overproduced oxidative biomarkers alter plant cell homeostasis. In contrast, APX (25.56 %) and GR (32.45 %) activities, chlorophyll (15.51 %) and carotenoids (30 %) contents increased under similar Pb treatments and regulated ROS-antioxidant balance. Exogenous S application, maintained the redox status of cell by further increasing the enzymatic activities. Pbtreatment increased S assimilation in Brassicaby elevating enzyme activities of ATPS andOASTL, which was further augmented by S supplementation toPb-stressed plants. Besides gene expression of BjSULT, BjOASTL and BjGR1 exhibited slight increase under Pb stress, S application to the stressed plants doubled the expression and assisted the stress resistance. Overall, our findings demonstrate that S protect Pb-stressed Brassica seedlings, implying that S could be an ideal choicefor reducing Pb toxicity in crops.

Protective Mechanisms of Various Active Substances on Cell DNA Damage and Apoptosis Induced by Deoxynivalenol.

Deoxynivalenol (DON) is a secondary metabolite of fungi that is harmful to humans and animals. This study examined the protective effects of natural substances, including resveratrol, quercetin, vitamin E, vitamin C, and microbe-derived antioxidants (MA), on both human gastric mucosal cells (GES-1) and pig small intestinal epithelial cells (IPEC-1) when induced by DON. Cells were incubated with active substances for 3 h and then exposed to DON for 24 h. The oxidative stress index, cell cycle, and apoptosis were measured. As compared to cells treated only with DON, pretreatment with active substances improved the balance of the redox status in cells caused by DON. Specifically, quercetin, vitamin E, vitamin C, and MA showed the potential to alleviate the G2 phase cell cycle arrest effect that was induced by DON in both kinds of cells. It was observed that vitamin E and vitamin C can alleviate DON-induced apoptosis and the G2 phase cycle arrest effect mediated via the ATM-Chk 2-Cdc 25C and ATM-P53 signaling pathways in GES-1 cells. In IPEC-1 cells, vitamin C and MA can alleviate both DON-induced apoptosis and the G2 phase cycle arrest effect via the ATM-Chk 2-Cdc 25C signaling pathway. Different bioactive substances utilize different protective mechanisms against DON in interacting with different cells. The proper addition of vitamin E and vitamin C to food can neutralize the toxic effect of DON, while the addition of vitamin C and MA to animal feed can reduce the harm DON does to animals.

Sound waves alter the viability of tobacco cells via changes in cytosolic calcium, membrane integrity, and cell wall composition.

The effect of sound waves (SWs) on plant cells can be considered as important as other mechanical stimuli like touch, wind, rain, and gravity, causing certain responses associated with the downstream signaling pathways on the whole plant. The objective of the present study was to elucidate the response of suspension-cultured tobacco cells (Nicotiana tabacum L. cv Burley 21) to SW at different intensities. The sinusoidal SW (1,000 Hz) was produced through a signal generator, amplified, and beamed to the one layer floating tobacco cells inside a soundproof chamber at intensities of 60, 75, and 90 dB at the plate level for 15, 30, 45, and 60 min. Calibration of the applied SW intensities, accuracy, and uniformity of SW was performed by a sound level meter, and the cells were treated. The effect of SW on tobacco cells was monitored by quantitation of cytosolic calcium, redox status, membrane integrity, wall components, and the activity of wall modifying enzymes. Cytosolic calcium ions increased as a function of sound intensity with a maximum level of 90 dB. Exposure to 90 dB was also accompanied by a significant increase of H2O2 and membrane lipid peroxidation rate but the reduction of total antioxidant and radical scavenging capacities. The increase of wall rigidity in these cells was attributed to an increase in wall-bound phenolic acids and lignin and the activities of phenylalanine ammonia-lyase and covalently bound peroxidase. In comparison, in 60- and 75 dB, radical scavenging capacity increased, and the activity of wall stiffening enzymes reduced, but cell viability showed no changes. The outcome of the current study reveals that the impact of SW on plant cells is started by an increase in cytosolic calcium. However, upon calcium signaling, downstream events, including alteration of H2O2 and cell redox status and the activities of wall modifying enzymes, determined the extent of SW effects on tobacco cells.

Inhibition of glycogen synthase kinase-3 enhances NRF2 protein stability, nuclear localisation and target gene transcription in pancreatic beta cells

Accumulation of reactive oxygen species (i.e., oxidative stress) is a leading cause of beta cell dysfunction and apoptosis in diabetes. NRF2 (NF-E2 p45-related factor-2) regulates the adaptation to oxidative stress, and its activity is negatively regulated by the redox-sensitive CUL3 (cullin-3) ubiquitin ligase substrate adaptor KEAP1 (Kelch-like ECH-associated protein-1). Additionally, NRF2 is repressed by the insulin-regulated Glycogen Synthase Kinase-3 (GSK3). We have demonstrated that phosphorylation of NRF2 by GSK3 enhances β-TrCP (beta-transducin repeat-containing protein) binding and ubiquitylation by CUL1 (cullin-1), resulting in increased proteasomal degradation of NRF2. Thus, we hypothesise that inhibition of GSK3 activity or β-TrCP binding upregulates NRF2 and so protects beta cells against oxidative stress. We have found that treating the pancreatic beta cell line INS-1 832/13 with the KEAP1 inhibitor TBE31 significantly enhanced NRF2 protein levels. The presence of the GSK3 inhibitor CT99021 or the β-TrCP-NRF2 protein-protein interaction inhibitor PHAR, along with TBE31, resulted in prolonged NRF2 stability and enhanced nuclear localisation (P < 0.05). TBE31-mediated induction of NRF2-target genes encoding NAD(P)H quinone oxidoreductase 1 (Nqo1), glutamate-cysteine ligase modifier (Gclm) subunit and heme oxygenase (Hmox1) was significantly enhanced by the presence of CT99021 or PHAR (P < 0.05) in both INS-1 832/13 and in isolated mouse islets. Identical results were obtained using structurally distinct GSK3 inhibitors and inhibition of KEAP1 with sulforaphane. In summary, we demonstrate that GSK3 and β-TrCP/CUL1 regulate the proteasomal degradation of NRF2, enhancing the impact of KEAP1 regulation, and so contributes to the redox status of pancreatic beta cells. Inhibition of GSK3, or β-TrCP/CUL1 binding to NRF2 may represent a strategy to protect beta cells from oxidative stress.

Osteoblastic differentiation and changes in the redox state in pulp stem cells by laser treatment

The aim of this study was to determine the effect of low-level laser therapy (LLLT) on cell proliferation, mitochondrial membrane potential changes (∆Ψm), reactive oxygen species (ROS), and osteoblast differentiation of human dental pulp stem cells (hDPSCs). These cells were irradiated with 660- and 940-nm lasers for 5 s, 50 s, and 180 s. Cell proliferation was assessed using the resazurin assay, cell differentiation by RUNX2 and BMP2 expression, and the presence of calcification nodules using alizarin-red S staining. ROS was determined by the dichlorofluorescein-diacetate technique and changes in ∆Ψm by the tetramethylrhodamine-ester assay. Data were analyzed by a Student’s t-test and Mann–Whitney U test. The 940-nm wavelength for 5 and 50 s increased proliferation at 4 days postirradiation. After 8 days, a significant decrease in proliferation was observed in all groups. Calcification nodules were evident in all groups, with a greater staining intensity in cells treated with a 940-nm laser for 50 s, an effect that correlated with increased RUNX2 and BMP2 expression. ROS production and Δψm increased independently of irradiation time. In conclusion, photobiomodulation (PBM) with LLLT induced morphological changes and reduced cell proliferation rate, which was associated with osteoblastic differentiation and increased ROS and Δψm, independent of wavelength and time.

Synthesis of Mn2O3 Nanoparticles and Determination of Its Inhibition Effect On Sera of Iraqi Patients with Diabetes Mellitus Type-2 and Diabetes Nephropathy

Manganese is essential for the synthesis of antioxidant enzymes and metabolic issues in Diabetes type 2 (DMT2), which is a worldwide disease, Chronic metabolic disorders cause insulin resistance, hyperglycemia, and complications like diabetic nephropathy. Arginase converts arginine to ornithine and urea. Increased arginase activity in DMT2 and diabetes nephropathy (DN)which has been linked to kidney damage, and arginase inhibitors can increase NO which is essential to vascular function. However, the molecular mechanisms of arginased is regulationare in DMT2 and DN are still unclear. This study examined the effect of manganese oxide nanoparticles (Mn2O3NPs) on arginase activity inhibition inserum samples from DMT2 and DN patients. We hypothesized that Mn2O3NPs alter cell redox status and signaling pathways, affecting DMT2 and DN arginase activity. We used a colorimetric assay to measure arginase activity in 80 serum samples from DMT2 and DN patients treated with different MnO2 NP concentrations to test our hypothesis. The current study characterized nanoparticles using various techniques such as IR, SEM, AFM, XRD, and EDX, which found it within nanoscale nature. Our findings are that Mn2O3NPs modulate arginase activity specificity in DM2 samples. SuggestionsMn2O3NPs could be used to develop new treatments for these conditions.

Attenuation of carbon tetrachloride-induced nephrotoxicity by gum Arabic extract via modulating cellular redox state, NF-κB pathway, and KIM-1

The current study investigated the ameliorating impact of GA water extract (GAE) on CCl4-induced nephrotoxicity in renal cells and tissue by comparing its effectiveness with the Ketosteril (Ks) drug in restoring oxidative stress and necroinflammation. The cell morphology, necrosis, and redox state were evaluated in Vero cells. The influence of GAE on CCl4-induced oxidative stress, inflammation, and necrosis was examined in rats. The predicted inhibitory mechanism of GAE phenolic constituents against COX-2 and iNOS was also studied. The results revealed that GAE contains crucial types of phenolic acids, which are associated with its antiradical activities. GAE improved CCl4-induced Vero cell damage and restored renal architecture damage, total antioxidant capacity, ROS, TBARS, NO, GSH, GPX, SOD, and MPO in rats. GAE downregulated the gene expression of renal NF-κB, TNF-α, iNOS, and COX-2, as well as kidney injury molecule-1 (KIM-1) in rats. The GAE improved blood urea, creatinine, cholesterol, and reducing power. The computational analysis revealed the competitive inhibitory mechanism of selected phenolic composites of GAE on COX-2 and iNOS activities. The GAE exhibited higher potency than Ks in most of the studied parameters, as observed by the heatmap plots. Thus, GAE is a promising extract for the treatment of kidney toxicity.

Nanomaterials-Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy.

Cancer cells typically display redox imbalance compared with normal cells due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This redox imbalance may regulate gene expression, alter protein stability, and modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra- or extracellular redox states of cancer cells at varying state of progression may trigger programmed cell death if exceeded a certain threshold, enabling therapeutic selectivity and overcoming cancer resistance to radiotherapy and chemotherapy. Nanotechnology provides new opportunities for modulating redox state in cancer cells due to their excellent designability and high reactivity. Various nanomaterials are widely researched to enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, or both. Here, the physiological features of redox imbalance in cancer cells are described and the challenges in modulating redox state in cancer cells are illustrated. Then, nanomaterials that regulate redox imbalance are classified and elaborated upon based on their ability to target redox regulations. Finally, the future perspectives in this field are proposed. It is hoped this review provides guidance for the design of nanomaterials-based approaches involving modulating intra- or extracellular redox states for cancer therapy, especially for cancers resistant to radiotherapy or chemotherapy, etc.

Alginate oligosaccharides exert protective effects on hydrogen peroxide-induced senescence in H9C2 cardiomyocytes by regulating the redox state of cells.

Aging is a known independent risk factor for several cardiovascular diseases. Here, we evaluated potential effects and possible mechanisms through which alginate oligosaccharides (AOS) affect hydrogen peroxide (H2O2)-induced senescence in H9C2 cardiomyocytes. A series of AOS molecules, including oligoM, oligoG, M-5, and G-5, were investigated. AOS significantly decreased SA-β-gal and DAPI-stained positive cells, downregulated p53 and p21 (aging-related markers) expression, and eventually protected H9C2 cells from H2O2-induced senescence. AOS decreased reactive oxygen species and malondialdehyde production, recovered mitochondrial function, and alleviated the oxidative stress state by regulating PGC-1α and NADPH oxidase subunit expression. Furthermore, AOS treatment restored the expression of antioxidant enzymes in senescent H9C2 cells. Thus, our results show in vitro evidence that AOS alleviate senescence in H9C2 cells by regulating the redox state; thus, AOS may be an effective therapeutic agent that could protect against cardiomyocyte senescence.

Novel N-pyrocatechoyl and N-pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity.

Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress-associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N-pyrocatechoyl and N-pyrogalloyl hydrazones (N-PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N-PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT-116 cells and healthy fibroblasts MRC-5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone-type hybrids encouraged investigations on G+ and G- bacterial strains, which revealed the antibacterial potency of several N-PYRs. These findings highlighted the N-PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.

Awakening adult neural stem cells: NOX signalling as a positive regulator of the quiescence-to-proliferation transition in the Xenopus retina.

A growing wealth of data suggest that reactive oxygen species (ROS) signalling might be crucial in conferring embryonic or adult stem cells their specific properties. However, how stem cells control ROS production and scavenging, and how ROS in turn contribute to stemness, remain poorly understood. Using the Xenopus retina as a model system, we first investigated the redox status of retinal stem cells (RSCs). We discovered that they exhibit higher ROS levels compared with progenitors and retinal neurons, and express a set of specific redox genes. We next addressed the question of ROS functional involvement in these cells. Using pharmacological or genetic tools, we demonstrate that inhibition of NADPH oxidase-dependent ROS production increases the proportion of quiescent RSCs. Surprisingly, this is accompanied by an apparent acceleration of the mean division speed within the remaining proliferating pool. Our data further unveil that such impact on RSC cell cycling is achieved by modulation of the Wnt/Hedgehog signalling balance. Altogether, we highlight that RSCs exhibit distinctive redox characteristics and exploit NADPH oxidase signalling to limit quiescence and fine-tune their proliferation rate.

Regulation of Nrf2/Keap1 signaling pathway in cancer drug resistance by galectin-1: cellular and molecular implications.

Oxidative stress is characterized by the deregulation of the redox state in the cells, which plays a role in the initiation of various types of cancers. The activity of galectin-1 (Gal-1) depends on the cell redox state and the redox state of the microenvironment. Gal-1 expression has been related to many different tumor types, as it plays important roles in several processes involved in cancer progression, such as apoptosis, cell migration, adhesion, and immune response. The erythroid-2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling pathway is a crucial mechanism involved in both cell survival and cell defense against oxidative stress. In this review, we delve into the cellular and molecular roles played by Gal-1 in the context of oxidative stress onset in cancer cells, particularly focusing on its involvement in activating the Nrf2/Keap1 signaling pathway. The emerging evidence concerning the anti-apoptotic effect of Gal-1, together with its ability to sustain the activation of the Nrf2 pathway in counteracting oxidative stress, supports the role of Gal-1 in the promotion of tumor cells proliferation, immuno-suppression, and anti-tumor drug resistance, thus highlighting that the inhibition of Gal-1 emerges as a potential strategy for the restraint and regression of tumor progression. Overall, a deeper understanding of the multi-functionality and disease-specific expression profiling of Gal-1 will be crucial for the design and development of novel Gal-1 inhibitors as anticancer agents. Excitingly, although it is still understudied, the ever-growing knowledge of the sophisticated interplay between Gal-1 and Nrf2/Keap1 will enable researchers to gain valuable insights into the underlying causes of carcinogenesis and metastasis.

Monitoring alterations of all-trans-retinal in human brain cancer cells by label-free confocal Raman imaging: regulation of the redox status of cytochrome c.

This article has shown the impact of all-trans-retinal on human brain cancer, which is apparent in the shifts in the redox status of cytochrome c in a single cell. The connection between cytochrome c expression and its role in cancer development remains relatively unexplored. To assess this, we employed Raman spectroscopy and imaging to determine the redox state of the iron ion in cytochrome c across different cellular locations, including mitochondria, cytoplasm, lipid droplets, and the endoplasmic reticulum within human brain cancer cells. We have analyzed normal human astrocytes (NHA) and two brain cancer cell lines (astrocytoma - CRL-1718 and glioblastoma - U-87 MG) without and supplemented with all-trans-retinal. Our results confirmed that human brain cancer cells demonstrate varying redox status compared to normal cells based on the established correlation between the intensity of the cytochrome c Raman band at 1583 cm-1 and the malignancy grade of brain cancer cells. Our research unveiled that all-trans-retinal induces remarkable changes in the mitochondrial functional activity (redox status) of cancer cells, which were measured by confocal Raman spectroscopy and imaging.