Expression Of Superoxide Dismutase Research Articles

Resveratrol Mitigates Ischemia/Reperfusion-Induced Cardiomyocyte Injury by Inhibiting the Expression of Superoxide Dismutase 2

Resveratrol exhibits antioxidant, anti-inflammatory, and potentially cardio-protective properties. However, the effectiveness of resveratrol in acute myocardial infarction (AMI)-induced cardiomyocyte injury remains unclear. Superoxide Dismutase 2 (SOD2) is an important antioxidant enzyme in the mitochondria. However, few studies have reported the impact of SOD2 on AMI-induced cardiomyocyte injury. Therefore, we establish an in vitro model of cardiomyocyte ischemia/reperfusion (I/R) injury using oxygen-glucose deprivation/reoxygenation (OGD/R) to investigate the protective effects of resveratrol against OGD/R-induced cardiomyocyte injury and its underlying regulatory mechanism. Cell viability was assessed using the CCK-8. Apoptosis was evaluated by TUNEL staining. The levels of Cleaved cas-3, Bcl2, and SOD2 an important antioxidant enzyme in the mitochondria that is responsible for eliminating superoxide radicals were analyzed by western blot. The ROS positive rate was using a ROS/Superoxide detection assay kit. The relative abundance of the SOD2 mRNA was determined using the 2−ΔΔCT method. We demonstrated that OGD/R treatment significantly reduced AC16 cell viability while increasing apoptosis levels, oxidative stress, and inflammatory factor levels. We further confirmed the upregulation of SOD2 by OGD/R treatment, suggesting its potential involvement in modulating OGD/R-induced AC16 cell injury. Additionally, silencing SOD2 ameliorated the detrimental effects of OGD/R on AC16 cells. Moreover, we observed that upregulation of SOD2 aggravated OGD/R-induced AC16 cell injury, and resveratrol effectively reduced OGD/R-induced AC16 cell injury by down-regulating SOD2. In conclusion, this research provides a promising therapeutic strategy for mitigating I/R damage in AMI-induced cardiomyocytes, thereby identifying a potential target for therapeutic intervention.

Repair Effect of Umbilical Cord Mesenchymal Stem Cells Embedded in Hydrogel on Mouse Insulinoma 6 Cells Injured by Streptozotocin.

Umbilical cord mesenchymal stem cells (UC-MSCs) possess the capabilities of differentiation and immune modulation, which endow them with therapeutic potential in the treatment of type 2 diabetes mellitus (T2DM). In this study, to investigate the repair mechanism of UC-MSCs in hydrogel on pancreatic β-cells in diabetes, mouse insulinoma 6 (MIN-6) cells damaged by streptozotocin (STZ) in vitro were used in co-culture with UC-MSCs in hydrogel (UC-MSCs + hydrogel). It was found that UC-MSCs + hydrogel had a significant repair effect on injured MIN-6 cells, which was better than the use of UC-MSCs alone (without hydrogel). After repair, the expression of superoxide dismutase (SOD) and catalase (CAT) as well as the total antioxidant capacity (T-AOC) of the repaired MIN-6 cells were increased, effectively reducing the oxidative stress caused by STZ. In addition, UC-MSCs + hydrogel were able to curb the inflammatory response by promoting the expression of anti-inflammatory factor IL-10 and reducing inflammatory factor IL-1β. In addition, the expression of both nuclear antigen Ki67 for cell proliferation and insulin-related genes such as Pdx1 and MafA was increased in the repaired MIN-6 cells by UC-MSCs + hydrogel, suggesting that the repair effect promotes the proliferation of the injured MIN-6 cells. Compared with the use of UC-MSCs alone, UC-MSCs + hydrogel exhibit superior antioxidant stress resistance against injured MIN-6 cells, better proliferation effects and a longer survival time of UC-MSCs because the porous structure and hydrophilic properties of the hydrogel could affect the growth of cells and slow down their metabolic activities, resulting in a better repair effect on the injured MIN-6 cells.

Potential protective effect of alpha lipoic acid against testicular oxidative stress and altered gene expression induced by gentamicin treatment

Background: Gentamicin induces testicular damage in association with oxidative stress explained by different mechanisms, including gene expression suppression of some antioxidant enzymes. The aim of the study: To investigate the potential protective effects of α-lipoic acid against gentamicininduced testicular oxidative stress in terms of altered gene expression. Materials and methods: A parallel experimental study was conducted including fifty adult male albino rats. The animals were grouped into five. The control group received intraperitoneal NaCl 0.9%, while the other groups received 36.5mg/kg/day intraperitoneal gentamicin. Group-1 received gentamicin only, group-2 received gentamicin + intraperitoneal α-lipoic acid 100mg/kg/day, group-3 received gentamicin + intraperitoneal α-lipoic acid 200mg/kg/day, and group-4 received gentamicin + oral vitamin E 100mg/kg/day. All treatments were given for 14 days. The animals were euthanized in two halves on the 15th and 60th days. Testes were immediately removed, frozen, and evaluated for oxidative stress biomarkers and gene expression of antioxidant enzymes. Results: Gentamicin increased malondialdehyde by mean difference ± standard error of 115.57 ± 2.18, decreased total antioxidant capacity by -9.23 ± 0.27, and decreased catalase and superoxide dismutase activities by -1.89 ± 0.45 and -11.77 ± 2.86, respectively, compared to the control. Additionally, gentamicin downregulated gene expression of catalase, glutathione peroxidase, and superoxide dismutase. However, adding vitamin E or α-lipoic acid cured the oxidative stress and partially to completely upregulated the gene expression. Conclusion: Reversal of testicular oxidative and gene suppression associated with gentamicin could be achieved with α-lipoic acid co-treatment, which might be applied in human studies.

Low expression of selenoprotein S induces oxidative damage in cartilages

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

MiR-224-5p overexpression inhibits oxidative stress by regulating the PI3K/Akt/FoxO1 axis to attenuate hypoxia/reoxygenation-induced cardiomyocyte injury

To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation (H/R) -induced H9c2 cardiomyocyte injury. Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC) to measure miRNA-224-5p levels and other biochemical parameters. In cultured H9c2 cells with H/R injury, the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability, malondialdehyde (MDA) content, and superoxide dismutase 2 (SOD2) and lactate dehydrogenase (LDH) activities were tested. Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN. Bioinformatics methods were used to analyze the potential mechanisms of the target genes. The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR, the protein expressions of PTEN, Bcl-2, Bax, cleaved caspase-3, SOD2, p-PI3K/PI3K, p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting, and cell apoptosis was analysed with flow cytometry. The levels of blood glucose, C-reactive protein, CK, CK-MB and cTnI were significantly higher in the AMI group compared with the HC group (P < 0.05). The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury. The viability of H9c2 cells decreased time-dependently following H/R injury. PTEN was a target gene of miR-224-5p, and the PI3K/Akt pathway was the most significantly enriched pathway. H9c2 cells with H/R injury showed significantly decreased SOD2 activity, increased LDH activity and MDA content, increased cell apoptosis, decreased protein expression levels of p-PI3K, p-Akt, p-FoxO1, SOD2, and Bcl-2, and increased expressions of PTEN, Bax, and cleaved caspase-3. These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure. MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.

Role of Corn Peptide Powder in Lipopolysaccharide-Induced Inflammatory Responses in 3T3-L1 Adipocytes.

Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing obesity-related disorders, but its impact on reducing inflammation is unknown. Hence, this study examined the possible protective effects of corn peptide powder (CPP) against the harmful effects of lipopolysaccharide (LPS), with a particular emphasis on reducing oxidative damage and inflammation in adipocytes. Hence, mature 3T3-L1 adipocytes underwent exposure to 10 ng/mL LPS, with or without CPP (10 and 20 μg/mL). LPS stimulation increased reactive oxygen species and superoxide anion generation. However, this effect was reduced in a dose-dependent manner by pretreatment with CPP. CPP treatment elevated the mRNA expressions of the antioxidant enzymes manganese superoxide dismutase (mnSOD) and glutathione peroxidase 1 (Gpx1) while reducing the mRNA expressions of the cytosolic reactive oxygen species indicators p40 and p67 (NADPH oxidase 2). In addition, CPP inhibited the monocyte chemoattractant protein-1, tumor necrosis factor-alpha, Toll-like receptor 4, and nuclear factor kappa B mRNA expressions induced by LPS. These findings demonstrate that CPP may ameliorate adipocyte dysfunction by suppressing oxidative damage and inflammatory responses through a new mechanism known as Toll-like receptor 4/nuclear factor kappa B-mediated signaling.

Extraction optimization, physicochemical properties, and inhibitory effect against tobacco mosaic virus of the protein from discarded tobacco leaves

Plant proteins have been attracting increasing attention due to their significant antiviral activity against tobacco mosaic virus (TMV). This paper aimed to investigate the tobacco endogenous protein and the anti-TMV effects. Firstly, the extraction of protein from discarded tobacco leaves (DTLP) was optimized by response surface methodology (RSM). The maximum DTLP yield reached to 8.32 % under the condition of solid-liquid ratio 1:19, temperature 60 °C and pH 12. DTLP was rich in hydrophilic amino acids, such as aspartic acid (8.08 ± 0.34 g/100 g) and glutamic acid (8.02 ± 0.42 g/100 g). DTLP structure was compact and stable with a denaturation temperature of 99.7 °C. Furthermore, the anti-TMV experiments revealed that DTLP showed inactive and protective activities against TMV with inhibitory rates (79.2 % and 75.4 %, respectively) at 500 µg/mL, and inhibited the polymerization of TMV-CP to damage TMV particles. In addition, DTLP increased the expressions of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and phenylalanine ammonia lyase (PAL) in tobacco leaves by 1.55, 1.18, 9.13 and 2.92 times, respectively. Transcriptomics further verified that DTLP increased the expressions of TGA, WRKY, and PR1 genes for up-regulating the salicylic acid (SA) and pathogenesis-related proteins (PRs), thereby improving the system resistance of tobacco plants. Therefore, DTLP could be potentially developed as an alternative drug to treat plant viral diseases due to its broad-spectrum anti-TMV activity.

Metabolic and Functional Interactions of H2S and Sucrose in Maize Thermotolerance through Redox Homeodynamics.

Hydrogen sulfide (H2S) is a novel gasotransmitter. Sucrose (SUC) is a source of cellular energy and a signaling molecule. Maize is the third most common food crop worldwide. However, the interaction of H2S and SUC in maize thermotolerance is not widely known. In this study, using maize seedlings as materials, the metabolic and functional interactions of H2S and SUC in maize thermotolerance were investigated. The data show that under heat stress, the survival rate and tissue viability were increased by exogenous SUC, while the malondialdehyde content and electrolyte leakage were reduced by SUC, indicating SUC could increase maize thermotolerance. Also, SUC-promoted thermotolerance was enhanced by H2S, while separately weakened by an inhibitor (propargylglycine) and a scavenger (hypotaurine) of H2S and a SUC-transport inhibitor (N-ethylmaleimide), suggesting the interaction of H2S and SUC in the development of maize thermotolerance. To establish the underlying mechanism of H2S-SUC interaction-promoted thermotolerance, redox parameters in mesocotyls of maize seedlings were measured before and after heat stress. The data indicate that the activity and gene expression of H2S-metabolizing enzymes were up-regulated by SUC, whereas H2S had no significant effect on the activity and gene expression of SUC-metabolizing enzymes. In addition, the activity and gene expression of catalase, glutathione reductase, ascorbate peroxidase, peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, and superoxide dismutase were reinforced by H2S, SUC, and their combination under non-heat and heat conditions to varying degrees. Similarly, the content of ascorbic acid, flavone, carotenoid, and polyphenol was increased by H2S, SUC, and their combination, whereas the production of superoxide radicals and the hydrogen peroxide level were impaired by these treatments to different extents. These results imply that the metabolic and functional interactions of H2S and sucrose signaling exist in the formation of maize thermotolerance through redox homeodynamics. This finding lays the theoretical basis for developing climate-resistant maize crops and improving food security.

Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming.

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti-cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.

Nesfatin-1 mitigates calcific aortic valve disease via suppressing ferroptosis mediated by GSH/GPX4 and ZIP8/SOD2 axes

ObjectiveCalcific aortic valve disease (CAVD) predominantly affects the elderly and currently lacks effective medical treatments. Nesfatin-1, a peptide derived from the cleavage of Nucleobindin 2, has been implicated in various calcification processes, both physiological and pathological. This study explores the impact of Nesfatin-1 on the transformation of aortic valve interstitial cells (AVICs) in CAVD. Methods and resultsIn vitro experiments showed that Nesfatin-1 treatment mitigated the osteogenic differentiation of AVICs. Corresponding in vivo studies demonstrated a deceleration in the progression of CAVD. RNA-sequencing of AVICs treated with and without Nesfatin-1 highlighted an enrichment of the Ferroptosis pathway among the top pathways identified by the Kyoto Encyclopedia of Genes and Genomes analysis. Further examination confirmed increased ferroptosis in both calcified valves and osteoblast-like AVICs, with a reduction in ferroptosis following Nesfatin-1 treatment. Within the Ferroptosis pathway, ZIP8 showed the most notable modulation by Nesfatin-1. Silencing ZIP8 in AVICs increased ferroptosis and osteogenic differentiation, decreased intracellular Mn2+ concentration, and reduced the expression and activity of superoxide dismutase (SOD2). Furthermore, the silencing of SOD2 exacerbated ferroptosis and osteogenic differentiation. Nesfatin-1 treatment was found to elevate the expression of glutathione peroxidase 4 (GPX4) and levels of glutathione (GSH), as confirmed by Western blotting and GSH concentration assays. ConclusionIn summary, Nesfatin-1 effectively inhibits the osteogenic differentiation of AVICs by attenuating ferroptosis, primarily through the GSH/GPX4 and ZIP8/SOD2 pathways.

Aspartame, as an artificial sweetener, does not affect renal function and antioxidative states in mice

Background and objectiveAspartame (l-aspartyl l-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys.MethodsIn this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame’s effect on kidneys via histological analysis.ResultsThere were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups.ConclusionOur findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states.

The effect of an antioxidant gel compared to chlorhexidine during the soft tissue healing process: An animal study.

Prolonged inflammation and oxidative stress can impede healing. To enhance healing efficiency, many solutions have been employed. This is an in vivo study comparing chlorhexidine (CHX) to a commercial antioxidant gel (AO). Envelope flaps were created in the lower incisor gingival region of 60 Sprague-Dawley rats, and acellular dermal matrix (ADM) was inserted. Animals were randomly assigned to postsurgical treatment application of AO gel or 0.12% CHX twice daily. A control group received no postsurgical treatment. Data collected (before surgery, 24 h, and 72 h) included surgical images, tissue samples, and weights. Blinded scorers assessed images using a wound healing scale. Real-time polymerase chain reaction (RT-PCR) was used for gene expression of tumor necrosis factor-alpha (TNFα), interleukin-1 (IL-1), myeloperoxidase (MPO), and superoxide dismutase (SOD). The AO group scored higher than the CHX and control groups in clinical evaluation (p<0.05). At 24h, TNFα expression was upregulated in the AO group compared to CHX (p=0.027) and controls (p=0.018). The AO group had significantly higher expression of antioxidant enzyme (SOD) at 24h compared to CHX (p=0.021). All animals lost weight in the first 24h. Animals treated with AO or CHX regained more weight at 72h than control animals (p=0.034 and 0.003, respectively). Animals treated with AO healed faster. AO led to earlier upregulation of TNFα and antioxidant enzyme SOD. We hypothesized that AO promoted an earlier inflammatory process while counteracting oxidative stress by increasing antioxidant responses via SOD.

Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and Caenorhabditis Elegans.

Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.

Effects of parity and week after calving on the metabolic, redox, and immune status of dairy cows

At the onset of lactation in dairy cows, inflammation and oxidative stress may occur and result in a risk of pathologies and lower milk yield. To propose an innovative management strategy for cows during this period, it is essential to better understand these physiological variations. Our objective was to evaluate the metabolic, redox and immune status of 7 primiparous and 8 multiparous Holstein cows during late gestation and the first months of lactation. Blood samples were collected between 3 weeks before calving until 12 weeks postpartum. Milk samples were also collected, but only at the time points after calving. The metabolic (nonesterified fatty acids (NEFA), BHB, glucose, urea, calcium) and redox (reactive oxygen metabolites (ROM), oxidative stress index (OSI), glutathione peroxidase activity, vitamin E) statuses were analyzed in plasma or erythrocytes. The expression of genes related to antioxidant functions was determined in leukocytes collected from milk. For immune status, plasma cytokine levels and the production of reactive oxygen species (ROS) in classical and regulatory neutrophils were measured in 2 whole blood ex vivo challenges. The data were analyzed using a mixed model that included the fixed effects of parity and week and their interaction. Milk yield, plasma NEFA and BHB in wk 2 and 4 after calving were higher in multiparous cows than in primiparous cows, whereas glucose and calcium tended to be lower. Plasma ROM and OSI levels in wk 8 were higher in multiparous than in primiparous cows. Multiparous cows also displayed higher glutathione peroxidase activity in erythrocytes, and antioxidant transcription factor and superoxide dismutase-1 expression levels in milk leukocytes. Moreover, multiparous cows had higher plasma concentrations of vitamin E but lower plasma levels of cytokines CXCL10, CCL2, IL1Rα and IFNγ. Following ex vivo whole blood stimulation with Escherichia coli, lower IL1α and TNFα levels were measured in multiparous than in primiparous cows. Intracellular ROS production by neutrophils was lower in multiparous than in primiparous cows. These results thus indicated marked physiological changes in wk 8 compared with wk 2 and 4 of lactation. These differences in the physiological status of primiparous and multiparous cows offer interesting perspectives for potential dietary strategies to prevent pathologies which take account of parity and week relative to calving.

Aconitum coreanum and processed products on its base prevent stroke via the PI3K/Akt and KEAP1/NRF2 in the in vivo study.

Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing.The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites.RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism.Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.

Protective Effects of the Postbiotic Levilactobacillus brevis BK3 against H2O2-Induced Oxidative Damage in Skin Cells.

Postbiotics have various functional effects, such as antioxidant, anti-inflammatory, and anti-obesity. Levilactobacillus brevis BK3, the subject of this study, was derived from lactic acid bacteria isolated from Kimchi, a traditional Korean fermented food. The antioxidant activity of BK3 was confirmed through the measurements of 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total antioxidant capacity (TAC). The wrinkle improvement effect was validated by assessing elastase inhibitory activity and collagenase inhibitory activity. The intracellular activity was confirmed using human keratinocytes (HaCaT) and human fibroblasts (HFF-1). BK3 protects skin cells from oxidative stress induced by H2O2 and reduces intracellular reactive oxygen species (ROS) production. In addition, the expressions of the antioxidant genes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were upregulated. Meanwhile, matrix metalloproteinase-1 (MMP-1) and collagen type I alpha 1 (COL1A1), involved in collagen degradation and synthesis, were significantly regulated. These results suggest the possibility of utilizing BK3 as a functional ingredient with antioxidant and wrinkle-improving effects.

Doxorubicin-induced neurotoxicity differently affects the hippocampal formation subregions in adult mice

Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it is associated with a long range of adverse effects, of which cognitive deficits stand out. The present study aimed to assess the neurologic adverse outcome pathways of two clinically relevant cumulative doses of DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching cumulative doses of 9 mg/kg (DOX9) or 18 mg/kg (DOX18). Animals were euthanized one week after the last administration, and biomarkers of oxidative stress and brain metabolism were evaluated in the whole brain. Coronal sections of fixed brains were used for specific determinations of the prefrontal cortex (PFC) and hippocampal formation (HF). In the whole brain, DOX18 tended to disrupt the antioxidant defences, affecting glutathione levels and manganese superoxide dismutase expression. Considering the regional analysis, DOX18 increased the volume of all brain areas evaluated, while GFAP-immunoreactive astrocytes decreased in the dentate gyrus (DG) and increased in the CA3 region of HF, both in a dose-dependent manner. Concerning the apoptosis pathway, whereas Bax increased in the DOX9 group, it decreased in the DOX18 group. Only in the latter group did Bcl-2 levels also decrease. While p53 only increased in the CA3 region of the DOX9 group, AIF increased in the PFC and DG of DOX18. Finally, phosphorylation of Tau decreased with the highest DOX dose in DG and CA3, while TNF-α levels increased in CA1 of DOX18. Our results indicate new pathways not yet described that could be responsible for the cognitive impairments observed in treated patients.

20- Deoxyingenol attenuate morphine-induced hippocampus neurotoxicity and memory impairments in rats

ObjectiveThe present study aimed to see if 20-Deoxyingenol(20-DOI) could protect hippocampus neurons from the neurotoxic effects of morphine and reduce memory loss in rats. MethodMale Wistar rats were given morphine hydrochloride (45 mg/kg, sc, four weeks) and 20-DOI (10, 20 mg/kg, ip., coadministered with morphine) for the Morris Water Maze (MWM) test to investigate the effects of 20-DOI on spatial learning and memory. Western blotting was used to evaluate the expression of the hippocampal CA1 region of the cleaved caspase-3, Bax, and Bcl2 proteins and so on. Moreover, these assays were used to evaluate the expression of superoxide dismutase (SOD)2, heme oxygenase 1(HO1) protein, and glutathione peroxidase (GPx) activity within the hippocampus CA1 area. ResultsThe administration of 20-DOI (10 and 20 mg/kg) to morphine-treated mice enhanced spatial learning and reduced memory deficits. Additionally, 20-DOI treatment reduced apoptosis and oxidative stress in the hippocampal CA1 region of morphine-treated rats. Moreover, 20-DOI improved the autophagy level of the hippocampal CA1 area of morphine-treated rats using Transcription factor EB (TFEB), and 20-DOI prevented spatial learning and memory impairment in morphine-treated rats. The current observation could be partially due to the inhibition of neuronal apoptosis and oxidative stress in the hippocampal CA1 region of rats treated with morphine and the improved autophagy in this region. Conclusions20-DOI attenuated morphine administration in rats with chronic disease caused spatial learning and memory dysfunction. These mechanistic effects could be partially related to 20-DOI protecting the CA1 region of rat hippocampal neurons from the morphine-induced oxidative stress, apoptosis, and autophagy through TFEB.

Cucumber PGIP2 is involved in resistance to gray mold disease

Polygalacturonase inhibitor protein (PGIP) restricts fungal growth and colonization and functions in plant immunity. Gray mold in cucumber is a common fungal disease caused by Botrytis cinerea, and is widespread and difficult to control in cucumber (Cucumis sativus L.) production. In this study, Cucumis sativus polygalacturonase-inhibiting protein 2 (CsPGIP2) was found to be upregulated in response to gray mold in cucumber. CsPGIP2 was detected in the endoplasmic reticulum, cell membrane, and cell wall after transient transformation of protoplasts and tobacco. A possible interaction between Botrytis cinerea polygalacturonase 3 (BcPG3) and CsPGIP2 was supported by protein interaction prediction and BiFC analysis. Transgenic Arabidopsis plants expressing CsPGIP2 were constructed and exhibited smaller areas of gray mold infection compared to wild type (WT) plants after simultaneous inoculation. Evans blue dye (EBD) confirmed greater damage for WT plants, with more intense dyeing than for the transgenic Arabidopsis. Interestingly, compared to WT, transgenic Arabidopsis exhibited higher superoxide dismutase (AtSOD1) expression, antioxidant enzyme activities, lignin content, net photosynthetic rate (Pn), and photochemical activity. Our results suggest that CsPGIP2 stimulates a variety of plant defense mechanisms to enhance transgenic Arabidopsis resistance against gray mold disease.

Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems.

Physiological stress such as excessive reactive oxygen species (ROS) production may contribute normal fibroblasts activation into cancer‑associated fibroblasts, which serve a crucial role in certain types of cancer such as pancreatic, breast, liver and lung cancer. The present study aimed to examine the cytoprotective effects of luteolin (3',4',5,7‑tetrahydroxyflavone) against hydrogen peroxide (H2O2)‑generated oxidative stress in lung fibroblasts. To examine the effects of luteolin against H2O2‑induced damages, cell viability, sub‑G1 cell population, nuclear staining with Hoechst 33342, lipid peroxidation and comet assays were performed. To evaluate the effects of luteolin on the protein expression level of apoptosis, western blot assay was performed. To assess the antioxidant effects of luteolin, detection of ROS using H2DCFDA staining, O2‑ and ·OH using electron spin resonance spectrometer and antioxidant enzyme activity was performed. In a cell‑free chemical system, luteolin scavenges superoxide anion and hydroxyl radical generated by xanthine/xanthine oxidase and the Fenton reaction (FeSO4/H2O2). Furthermore, Chinese hamster lung fibroblasts (V79‑4) treated with H2O2 showed a significant increase in cellular ROS. Intracellular ROS levels and damage to cellular components such as lipids and DNA in H2O2‑treated cells were significantly decreased by luteolin pretreatment. Luteolin increased cell viability, which was impaired following H2O2 treatment and prevented H2O2‑mediated apoptosis. Luteolin suppressed active caspase‑9 and caspase‑3 levels while increasing Bcl‑2 expression and decreasing Bax protein levels. Additionally, luteolin restored levels of glutathione that was reduced in response to H2O2. Moreover, luteolin enhanced the activity and protein expressions of superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase‑1. Overall, these results indicated that luteolin inhibits H2O2‑mediated cellular damage by upregulating antioxidant enzymes.