Measurement Of Malondialdehyde Research Articles

MiR-223-3p Targets KIF4A and Promotes the Oxidative Stress-Mediated Apoptosis of Breast Cancer Cells.

Background: The abnormal expression of kinase family member 4A (KIF4A) is linked to breast cancer progression, with numerous miRNAs exhibiting abnormal expression. Thus, there is an urgent need to investigate the mechanisms of action of miRNAs and their target genes for the diagnosis and treatment of breast cancer. Materials and Methods: A bioinformatics analysis was conducted to screen for KIF4A, a key gene involved in oxidative stress in breast cancer cells. Using CCK8, EdU, cell healing, and Transwell assays, the knockdown of KIF4A was found to effectively inhibit the proliferation, migration, and invasion of breast cancer cells. Dual-luciferase assay and Western blotting confirmed that miR-223-3p targets and regulates KIF4A expression. The impact of miR-223-3p and KIF4A on oxidative stress in breast cancer cells was assessed through reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) measurements. Flow cytometry was used to evaluate tumor cell apoptosis. Results: Our results suggest that KIF4A is a downstream target of miR-223-3p. miR-223-3p inhibits the proliferation and invasion of breast cancer cells by directly targeting and downregulating KIF4A. Importantly, we found that miR-223-3p and KIF4A play important roles in regulating oxidative stress and apoptosis in breast cancer cells. Specifically, miR-223-3p promoted apoptosis by inhibiting the expression of KIF4A, increasing the accumulation level of ROS and MDA, and inhibiting the activity of SOD while KIF4A was overexpressed.

Geraniol modulates inflammatory and antioxidant pathways to mitigate intestinal ischemia-reperfusion injury in male rats.

Intestinal ischemia-reperfusion injury (IIR/I) significantly increases morbidity and mortality. This study examines the therapeutic effects of geraniol (GNL), which is noted for its anti-inflammatory and antioxidant properties, on intestinal I/R injury in rats. Forty-nine male Wistar-Albino rats were divided into seven groups. After 30min of ischemia and subsequent reperfusion for either 1 or 6h, intestinal and hepatic tissues were analyzed. Biochemical assessments measured malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), and nitric oxide (NO) activities. Inflammatory and apoptotic markers were evaluated using qRT-PCR and ELISA, and apoptotic cell rates were determined by flow cytometry. GNL treatment significantly protected intestinal and hepatic tissues, enhancing antioxidant enzyme activity and normalizing MDA and NO activities. It demonstrated notable anti-inflammatory effects at 100 and 200mg/kg doses, reducing TNF-α, IL-1β, and IL-6 levels while decreasing tissue MPO content. GNL also increased Bcl-2 levels and decreased Bax levels, indicating anti-apoptotic effects. Serum activities of ALT, AST, and creatine kinase were lower in GNL-treated rats, and flow cytometry showed a reduction in apoptotic cells. GNL effectively mitigated oxidative stress and histopathological damage from intestinal I/R injury by reducing pro-apoptotic markers and increasing anti-apoptotic markers, highlighting its protective effects.

Discovery of novel flavonoid derivatives containing benzothiazole as potential antifungal agents.

Fungal diseases of plants have a serious impact on the quality and yield of crops, and some traditional pesticides can no longer cope with this problem. Therefore, it is of great significance to develop new pesticides with high efficiency and low toxicity. A series of flavonoid derivatives containing benzothiazole were designed and synthesized. Among them, the compounds V17, V12, and V13 had excellent inhibitory effect against Fusarium oxysporum f. sp. cucumerinu with the half-maximal effect concentration (EC50) values of 1.2, 2.3, and 3.2 μg/mL, which were better than the control drug Kresoxim-methyl (Km, 37.8 μg/mL). The in vivo protective activity and curative activities of V17 against cucumber fusarium wilt caused by F. oxysporum f. sp. cucumerinum were 82.4 and 60.5% at 200 μg/mL, better than Km (60.2 and 48.6%). In addition, V17 could damage the cell membrane of the mycelia, which can be confirmed by determination of cytoplasmic leakage, detection of cell membrane permeability, and measurement of malondialdehyde (MDA). Similarly, the scanning electron microscopy (SEM) experiment and optical microscope characterization provide direct evidence for destruction of mycelium treated with V17. V17 significantly reduced the pathogenicity of the F. oxysporum f. sp. cucumerinum, which provided a new idea and direction for the development of green pesticides. © 2025 Society of Chemical Industry.

Resveratrol alleviates depression-like behaviors by inhibiting ferroptosis via AKT/NRF2 pathway.

Major depressive disorder (MDD) is common, and successful treatment remains challenging. Resveratrol, a naturally occurring polyphenol, has been shown to alleviate depression-like behaviors, but the underlying mechanisms remain unclear. We previously developed a new model of depression by inducing hippocampal ferroptosis in rats, suggesting that ferroptosis may be involved in the development of MDD. Here, we further explored the antidepressant-like effect of resveratrol and its association with ferroptosis. Male rats were exposed to chronic unpredictable mild stress (CUMS), with or without resveratrol, followed by comprehensive behavioral testing. In PC12 cells in vitro, LY294002 (an AKT inhibitor) and ML385 (an NRF2 inhibitor) were used to elucidate the involvement of AKT/NRF2 signaling in resveratrol-mediated ferroptosis. mRNA and protein levels of AKT/NRF2 pathway and ferroptosis-related targets were measured. Ferroptosis was quantified by measuring malondialdehyde (MDA), glutathione (GSH), and Fe2+ content and superoxide dismutase (SOD) activity. Resveratrol ameliorated depression-like behaviors in rats, simultaneously restoring AKT/NRF2 pathway and ferroptosis-related targets in the hippocampus downregulated by CUMS. Elevated markers of oxidative stress in plasma were attenuated by resveratrol. Furthermore, erastin induced ferroptosis and inhibited AKT/NRF2 signaling in PC12 cells, which was counteracted by resveratrol. Additionally, the impact of resveratrol on erastin-induced ferroptosis was reversed by LY294002 and ML385. This study demonstrates that resveratrol ameliorates depression-like behaviors by inhibiting ferroptosis via the AKT/NRF2 pathway.

In Vitro and In Vivo Antioxidant Properties of P-Coumaroyl Alphitolic Acid Extracted from Fruit of Zizuphus mauritiana

Fruit of Zizuphus mauritiana has been commonly used in Traditional Medicine for its various pharmacological activities, such as its anticancer, antiepileptic, anti-inflammatory, anti-insomnia, neuroprotective effects and antioxidants. The aime of this study is to extract p-coumaroyl alphitolic acid compound present in fruit of Z. Mauritiana and to evaluate the antioxidant potential both in In-vitro and In-vivo effects. In-vitro antioxydant activities were assessed by DPPH, ABTS and FRAP methods. In-vivo antioxydant effects were evaluated in rats for 14 days, where different concentrations of p-coumaroyl alphitolic acid extracts (ACAE) (50, 100, 150, and 200 mg/kg/day) were orally administrated daily. Antioxidant profiles were performed by measuring malondialdehyde (MDA), blood proteins, reduced glutathione (GSH), glutathione peroxydase (GPX), catalase (CAT) and superoxide dismutase (SOD) activities in red blood cells. ACAE revealed excellent free radical scavenging activity (IC50) with DPPH (7.29 ± 0.94 µg/ml), ABTS (2.84 ± 0.07 µg/ml) and FRAP (28.32 ± 0.66 µg/ml) assay. Furthermore, CMAE decreased the level of MDA and SOD, and increased levels of GSH, GPX and CAT in blood. The results showed good antioxidant properties of ACAE of Zizuphus mauritiana fruit. Base on this results Jujube might be useful for the treatment of oxidative-stress related diseases such as chronic deseases.

Sustainable Use of Orange Peel Essential Oil: A Natural Antioxidant to Combat Fish Oil Oxidation

This study examines the protective effects of orange peel essential oil (OEo) against the oxidation of fish oil and its prospective application as an antioxidant. The investigation involved the addition of varying ratios of OEo (100 ppm-1600 ppm) to fish oil, and the protective effects against oxidation were assessed using measurements of peroxide value (PV) and malondialdehyde (MDA) generation. The accelerated oxidation test was conducted at a temperature of 55°C, 70% humidity, and continuous light for a duration of 120 hours. Furthermore, statistical disparities among the experimental groups were examined. The results indicated considerably reduced levels of PV and MDA (p

Potential of shallot peels as a daily antioxidant supplement against cigarette smoke-induced lung damage

Background: Cigarette smoking damages the alveoli through oxidative stress. Shallot peels containing flavonoids, especially quercetin, potentially serve as a daily antioxidant supplement to impede lung tissue damage induced by cigarette smoke. However, the maximum effective dose is yet to be determined. Objective: This research was designed to establish the maximum effective dose of shallot peel infusion (SPI) to prevent oxidative stress and histopathological lung damage induced by cigarette smoke. Methods: This experimental laboratory was a posttest-only control group design. A total of 24 male Rattus norvegicus Wistar strain, were allocated into 6 groups: a control group and 5 SPI-treated groups. All rats were exposed to 2 cigarettes/day and were treated for 28 days with aquabidest and different doses of SPI (0 mg/kgBW, 125 mg/kgBW, 250 mg/kgBW, 500 mg/kgBW, 1,000 mg/kgBW, and 2,000 mg/kgBW). The level of oxidative stress in serum was measured malondialdehyde (MDA) level with ELISA, and histopathological lung damage was estimated using the lung histopathological damage scoring method assessing inflammatory cells, alveolus lumen and inter-alveoli junction.Results: The quadratic regression analysis revealed the maximum effective dose of SPI to prevent oxidative stress and lung damage were 1,435 mg/kgBW and 1,206 mg/kgBW, respectively. In the histopathological examination of the lungs, the administration of SPI up to a dose of 1206 mg/kg BW prevents the inflammatory process caused by cigarette smoke, which is indicated by the number of inflammatory cells, the thickness of the alveolar septum, and the increasingly normal shape of the alveolar lumen.Conclusion: SPI doses of less than 1,206 mg/kgBW are safe and effective daily antioxidant supplements in rats exposed to cigarette smoke and have the potential to be further studied for application in humans.

High glucose Induces Podocyte Ferroptosis through BAP1/SLC7A11 Pathway

Ferroptosis plays an important role in the development of diabetic nephropathy (DN). However, its specific regulatory mechanisms remain unclear. MPC5 cells were cultured in high glucose (HG) medium to stimulate the HG environment in vitro. Ferroptosis and oxidative stress were assessed by measuring malondialdehyde (MDA) levels, cystine uptake capacity, and reactive oxygen species (ROS). C91A and wild type (WT) MPC5 cells were constructed to further explore the specific regulatory mechanism of BAP1 on SLC7A11. Erastin-induced ferroptosis was sensitized by HG, leading to a significant reduction in glutathione (GSH) levels, increased oxidative stress, and inhibited cystine uptake in podocytes. HG suppressed the expression of SLC7A11. Overexpression of SLC7A11 improved cystine uptake and reduced oxidative stress. Furthermore, HG increased BAP1 levels. Silencing BAP1 up-regulated SLC7A11 and mitigated ferroptosis. Cell proliferation was reduced after SLC7A11 knockdown. In BAP1 WT cells, but not in its C91A mutant cells, the transcription of SLC7A11 was downregulated and the level of ferroptosis was increased. HG inhibits cystine uptake in podocytes by promoting the expression of BAP1 and inhibiting H2Aub deubiquitination on SLC7A11, leading to lipid peroxide accumulation and ferroptosis in podocytes.

Extracellular Vesicles from Human iPSC‐derived NSCs Protect Human Neurons Against Aβ‐42 Induced Neurodegeneration, Mitochondrial Dysfunction and Tau Phosphorylation

AbstractBackgroundAlzheimer’s disease (AD) is characterized by the accumulation of amyloid‐beta (Aβ) in the extracellular space, which leads to various adverse effects such as oxidative stress, neuroinflammation, mitochondrial dysfunction, tau phosphorylation, synapse loss, and neurodegeneration. Therefore, therapeutic interventions that can reduce Aβ‐toxicity and slow down the progression of cognitive dysfunction in AD have significance. One promising approach is to use extracellular vesicles (EVs) that are released by neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs). These EVs contain therapeutic proteins and miRNAs that can help protect against Aβ‐induced pathological changes in the brain, providing a potential avenue for neuroprotection.MethodThis study first isolated and characterized EVs secreted from hiPSC‐NSCs by chromatographic methods. Next, mature human neurons generated from 2 different hiPSC lines were exposed to 1‐µM Aβ42 oligomers with different concentrations of hNSC‐EVs. The protective effects of EVs on neurons exposed to Aβ were quantified using MTT and live/dead cell assays and counting of surviving MAP‐2+ neurons. The extent of oxidative stress was investigated via measurements of malondialdehyde (MDA) and protein carbonyls (PCs) and the expression of genes encoding iNos and Cox2. Furthermore, the expression of genes and/or proteins linked to pro‐apoptotic (Bad, Bax) and antiapoptotic (Bcl2) effects, mitochondrial respiratory chain (Nudfs6, Nudfs7, Sdha, Sdhb, Cyc1, Bcs11, Cox6a1, Atp6ap1), autophagy (Beclin 1 and MAPILC3B) were quantified. Total tau and p‐tau were also measured.ResultThe addition of hiPSC‐NSC‐EVs to mature human neuronal cultures exposed to Aβ reduced the extent of Aβ‐induced neurodegeneration. When human neurons were exposed to Aβ‐42 alone, it increased pro‐apoptotic genes (Bad, Bax) and reduced the expression of an antiapoptotic gene (BCL‐2). However, adding hNSC‐EVs to Aβ‐42 exposed neurons normalized the expression of pro‐ and antiapoptotic genes to control levels, reduced oxidative stress markers, prevented Aβ‐42‐induced hyperactivation of mitochondria and decreased autophagy, reduced the phosphorylation of tau.ConclusionTreating human neurons with hiPSC‐NSC‐EVs can significantly decrease the various pathological changes caused by Aβ exposure. Supported by a grant from the National Institute for Aging (1RF1AG074256‐01A1 to A.K.S.)

Effects of different extraction temperatures on the structural characteristics and antioxidant activity of polysaccharides from dandelion leaves.

Dandelion polysaccharides contribute to a variety of biological activities. This study evaluated the effect of different extraction temperatures (4°C and 80°C) on the structural characteristics and antioxidant activity of dandelion leaf polysaccharides (DLP). The findings demonstrated that the extraction efficiency improved at the higher temperature, while molecular weight exist a trend of degradation with increasing extraction temperature. Ion chromatography (IC) analysis indicated that the polysaccharides DLP4 and DLP80 were structurally complex heteropolysaccharides mainly composed of galactose, arabinose, glucose and mannose, with galactose and arabinose dominating. FT-IR and methylation analysis revealed that DLP4 and DLP80 had similar chemical structures and branches. DLP4 contained a higher amount of 6-Galactose. Microstructure analysis showed that heat treatment caused conformational changes in DLP4 and DLP80. Both had excellent free radical scavenging ability including DPPH·, ABTS·+, OH· and reducing power. The Reactive Oxygen Species assay indicated that the protective effect of DLP4 against H2O2-induced oxidative damage in vitro was stronger than that of DLP80. Superoxide dismutase (SOD) and malondialdehyde (MDA) measurements also confirmed that the antioxidant effect of DLP4 was more prominent. Overall, low temperature extracted DLP can be used as an antioxidant in the areas of food, medicine and biomaterials.

Pro-oxidant Tetrapleura tetraptera polyphenol extract parallels quercetin as an in vitro cytotoxic agent in human liver cancer cells

Pro-oxidant Tetrapleura tetraptera polyphenol extract parallels quercetin as an in vitro cytotoxic agent in human liver cancer cells

Isorhamnetin ameliorates dopaminergic neuronal damage via targeting FOSL1 to activate AKT/mTOR in 6-OHDA-induced SH-SY5Y cells.

Parkinson's disease (PD) is a chronic neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra compacta, which may result from mitochondrial dysfunction and oxidative stress. Isorhamnetin (Iso) has important antioxidative stress and antiapoptotic effects, this study investigated the effects of Iso on PD in vitro and its underlying mechanisms using a model of 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cell damage. The results showed that Iso significantly ameliorated 6-OHDA-induced SH-SY5Y cell injury, including decreased cell viability, increased apoptosis and senescence, and oxidative stress injury. Senescence-associated β-galactosidase (SA-β) staining, Western blot (WB), and immunofluorescence suggested that Iso significantly decreased the number of SA-β+ cells and the levels of senescence-associated proteins p21 and p16, and enhanced tyrosine hydroxylase level. Iso markedly reduced the number of apoptotic cells and the levels of cleaved caspase-3 and BAX, as detected by CCK-8, flow cytometry, and WB. The results of DCFH-DA, JC-1 staining, and the measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) content indicated that Iso elevated reactive oxygen species (ROS) generation and mitochondrial membrane potential, lowered MDA content and raised SOD level in the 6-OHDA group. In-depth investigation revealed that Iso activated the AKT/mTOR signal via reducing the expression level of Fos-like antigen (FOSL1), which further exerted the protective effect in SH-SY5Y cells. Overexpression of FOSL1 attenuated the effect of Iso by inhibiting the AKT/mTOR signaling pathway. Taken together, Iso protects against senescence, apoptotic, and oxidative stress injury by targeting FOSL1 to activate the AKT/mTOR signaling pathway in 6-OHDA-induced SH-SY5Y cells, which may provide new insights for PD treatment.NEW & NOTEWORTHY Isorhamnetin (Iso) ameliorated neuronal activity damage, senescence, apoptosis, and oxidative stress injury in 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cells. Iso activated AKT/mTOR signaling pathway via inhibiting Fos-like antigen (FOSL1) in 6-OHDA-induced SH-SY5Y cells. Overexpression of FOSL1 attenuated the protective effect of Iso against 6-OHDA-induced neuronal damage in SH-SY5Y cells.

Salivary Markers of Oxidative Stress and Their Relation to Periodontal and Dental Status Among Children With Down Syndrome.

The current body of literature on oral health in individuals with Down syndrome (SD) presents contradictory information. Individuals with DS often have distinct oral health difficulties that set them apart from the general population. This study aimed to measure malondialdehyde (MDA) and total oxidant status (TOS) levels in the saliva of children diagnosed with DS and explore their association with oral health status. A cross-sectional study enrolled 82 participants aged 7-12, comprising 40 children with DS and 42 controls matched based on age and gender. Diagnosing dental caries relied on the guidelines provided by the World Health Organization. Oral hygiene was examined with the plaque index, and gingival health was estimated using the gingival index (GI). To evaluate oxidative stress, unstimulated whole saliva samples were gathered to measure levels of MDA and TOS. The study data were analyzed using Statistical Package for the Social Sciences version 22 (IBM Corp., Armonk, NY). The p value for parametric variables was obtained using Pearson's chi-square test and Fisher's exact test. In this study, there were no significant differences between the two groups regarding periodontal health and dental decay. However, children with DS displayed significantly elevated GI values compared to the control group (p = 0.05).Children with DS demonstrated significantly higher MDA levels than the control group (p < 0.001). Furthermore, DS children demonstrated a higher prevalence of dental caries in their primary teeth than their permanent teeth. Children with DS have comparable rates of dental caries to non-DS childrenbut show elevated levels of GI values. Furthermore, children with DS exhibit high levels of saliva MDA compared to their peers without DS. Future research should include a wider age range, additional oxidative stress markers, and factors like diet, lifestyle, and antioxidant supplementation. Longitudinal studies and quality-of-life assessments could offer deeper insights into the oral health of individuals with DS.

Mechanism of Gastrodin against neurotoxicity based on network pharmacology, molecular docking and experimental verification

Disorders of glutamate metabolism and excessive release participat in multiple neuronal pathologies including ischemic stroke (IS), Alzheimer's disease (AD), or Parkinson's disease (PD). Recently, herbal medicines have been widely used and have shown satisfactory results in the treatment of neurological disorders. Gastrodin is a traditional Chinese medicine (TCM) used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. This research examines the neuroprotective effects of Gastrodin against glutamate-induced neurotoxicity in neuronal cells. The HERB database was used to explore the active ingredients and target genes of Gastrodia Elata. The STRING database and Cytoscape software were used to screen and construct the Protein-Protein Interaction (PPI). Furthermore, we used molecular docking to predict the potential targets of Gastrodin. The effects of Gastrodin were revealed by western blot, calcium imaging, membrane clamp, CCK8 and flow cytometry. Neuronal oxidative stress and damage were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Neuronal morphology was examined using Golgi-Cox staining. Finally, animal behavior was examined using novel object recognition and fear conditioning tests. We have obtained 22 components such as TM10, TM17, TM25 (Gastrodin), and 281 targets such as AKT, EGFR, and CDK1 through network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed these genes were significantly enriched in protein phosphorylation, protein serine/threonine/tyrosine kinase activity, apoptosis and HIF-1 signaling pathways, etc. A higher affinity between Gastrodin and AKT was revealed by PPI analysis and molecular docking. Further, Gastrodin significantly inhibited Ca2+ influxes and excitatory synaptic transmission in cortical neurons. In addition, Gastrodin effectively alleviated neuron apoptosis, oxidative stress and damage. Gastrodin has neuroprotective effects against glutamate-induced neurotoxicity.

Modulating ferroptosis and mycobactericidal activity in lung epithelial cells via YY1/iNOS pathway

Mycobacterium tuberculosis infection triggers various forms of host cell death, including ferroptosis in lung epithelial cells; YY1, a critical transcription factor, plays a pivotal role in regulating ferroptosis, however, the underlying mechanisms are not fully understood. To investigate Mycobacterium marinum (M.marinum) infection in lung epithelial cells A549 and H1299, we utilized flow cytometry to evaluate cell death and measure reactive oxygen species (ROS). Colony-forming unit (CFU) assays determined the intracellular bacterial load. Ferroptosis was analyzed using a specific detection kit to measure malondialdehyde (MDA) and glutathione (GSH) levels. The interaction between the transcription factor YY1 and the iNOS promoter was assessed through a dual-luciferase reporter assay. M.marinum induced ferroptosis in lung epithelial cells through invasion. This effect is most pronounced at 8h of infection and decreases over time but increased with a higher multiplicity of infection (MOI). YY1 knockdown decreases the expression of SLC7A11 and GPX4, attenuates cellular ferroptosis, while YY1 overexpression has the opposite phenomenon, enhancing the expression of bactericidal molecules such as iNOS and MPEG1, thereby markedly reducing the intracellular bacterial load. We identified substantial binding of YY1 to the iNOS promoter region (-655 to -1018bp), enhancing mycobactericidal activity in YY1-overexpressing cells. Our study demonstrates that YY1 inhibits ferroptosis induced by Mycobacterium marinum infection and reduces intracellular bacterial proliferation in lung epithelial cells. These findings provide a crucial basis for developing anti-tuberculosis therapies that target YY1 modulation, potentially offering new clinical avenues for the treatment of tuberculosis.

The effect of major depressive disorder comorbidity on ischemia-modified albumin levels, a marker of oxidative stress, and antioxidant defense system in patients with obsessive compulsive disorder.

The aim of this study was to examine the levels of oxidant and antioxidant markers in patients with obsessive-compulsive disorder (OCD) and to investigate whether these levels change in the presence of major depressive disorder (MDD) comorbidity. This study was completed with 23 OCD patients with MDD comorbidity (OCD+MDD), 21 OCD patients without MDD comorbidity (OCD-MDD) and 21 healthy controls. Oxidative stress levels of the cases' were determined by ischemia modified albumin (IMA) and malondialdehyde (MDA) measurements and antioxidant levels were determined by superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) measurements. One-way analysis of variance (ANOVA) and unpaired Student's t-test were used to compare the study groups. Post hoc Bonferroni test was used for the degree of significance between groups, and repeated measures analysis of covariance (ANCOVA) was used to investigate the effect of age and gender. IMA and MDA levels were significantly higher in the OCD group compared to the control group, and SOD, CAT and GSH-Px levels were lower in the OCD group compared to the control group (p<0.01). IMA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group, while SOD, CAT and GSH-Px levels were significantly lower in the OCD+MDD group compared to the OCD-MDD group (p<0101). MDA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group (p=0.009). When the entire OCD patient group was examined, significant, powerful, positive correlations were observed between Y-BOCS and HDRS scores and IMA and MDA, and significant powerful negative correlations between Y-BOCS and HDRS scores and SOD, CAT, and GSH-Px (p<0.001 for all). In OCD+MDD group, oxidative stress markers increased significantly in parallel with the severity of depression, while antioxidant levels decreased (p=0.003 for IMA, p<0.001 for others). We believe that parameters indicating impaired oxidant/antioxidant balance in patients with obsessive-compulsive disorder may help to elucidate the cause of the disease and may be potentially useful biomarkers in the diagnosis and determination of the severity of comorbid MDD.

Synergistic ferroptosis in triple-negative breast cancer cells: Paclitaxel in combination with Erastin induced oxidative stress and Ferroportin-1 modulation in MDA-MB-231 cells.

Ferroptosis is an important regulated cell death mechanism characterized by iron-dependent lipid peroxidation and oxidative stress. In this study, we examined the ferroptosis-inducing effect of the combined use of Paclitaxel, a microtubule-stabilizing agent, and Erastin, a ferroptosis inducer, in breast cancer cells. In this context, the combination of the compounds in question was applied to the cells and the presence of a synergistic effect was determined by calculating the combination index. Glutathione (GSH) levels and glutathione peroxidase (GPX) activity were determined by commercial assay kits, and the effect of the compounds on lipid peroxidation was determined by measurement of malondialdehyde (MDA) levels. Additionally, the effect of combination treatment on ferroptotic protein expression was determined by western blot. Our findings revealed that the combination treatment caused a significant change in mitochondrial function by causing an increase in the depolarized/viable cell population. Additionally, there was a significant increase in intracellular reactive oxygen species (ROS) levels compared to single applications of the compounds. The significant increase observed in malondialdehyde (MDA) levels revealed that the combination treatment increased lipid peroxidation. Moreover, intracellular GSH levels and glutathione peroxidase (GPX) activity significantly decreased by Paclitaxel-Erastin combination. The expression of ferroptosis-regulating proteins was significantly downregulated. The findings showed that the Paclitaxel-Erastin combination synergistically contributed to the accumulation of lipid reactive oxygen species and induced the ferroptotic cell death pathway in breast cancer cells.

Minocycline alleviates lipopolysaccharide-induced cardiotoxicity by suppressing the NLRP3/Caspase-1 signaling pathway.

Minocycline (Min), as an antibiotic, possesses various beneficial properties such as anti-inflammatory, antioxidant, and anti-apoptotic effects. Despite these known qualities, the precise cardioprotective effect and mechanism of Min in protecting against sepsis-induced cardiotoxicity (SIC) remain unspecified. To address this, our study sought to assess the protective effects of Min on the heart. Lipopolysaccharide (LPS) was utilized to establish a cardiotoxicity model both in vivo and in vitro. Min was pretreated in the models. In the in vivo setting, evaluation of heart tissue histopathological injury was performed using hematoxylin and eosin (H&E) staining and TUNEL. Immunohistochemistry (IHC) was employed to evaluate the expression levels of NLRP3 and Caspase-1 in the heart tissue of mice. During in vitro experiments, the viability of H9c2 cells was gauged utilizing the CCK8 assay kit. Intracellular ROS levels in H9c2 cells were quantified using a ROS assay kit. Both in vitro and in vivo settings were subjected to measurement of oxidative stress indexes, encompassing glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Additionglly, myocardial injury markers like lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) activity were quantified using appropriate assay kits. Western blotting (WB) analysis was conducted to detect the expression levels of NOD-like receptor protein-3 (NLRP3), caspase-1, IL-18, and IL-1β, alongside apoptosis-related proteins such as Bcl-2 and Bax, and antioxidant proteins including superoxide dismutase-1 (SOD-1) and antioxidant proteins including superoxide dismutase-1 (SOD-2), both in H9c2 cells and mouse heart tissues. In vivo, Min was effective in reducing LPS-induced inflammation in cardiac tissue, preventing cell damage and apoptosis in cardiomyocytes. The levels of LDH and CK-MB were significantly reduced with Min treatment. In vitro studies showed that Min improved the viability of H9C2 cells, reduced apoptosis, and decreased ROS levels in these cells. Further analysis indicated that Min decreased the protein levels of NLRP3, Caspase-1, IL-18, and IL-1β, while increasing the levels of SOD-1 and SOD-2 both in vivo and in vitro. Min alleviates LPS-induced SIC by suppressing the NLRP3/Caspase-1 signalling pathway in vivo and in vitro.

CirSIRT5 induces ferroptosis in bladder cancer by forming a ternary complex with SYVN1/PHGDH

Bladder cancer (BC) represents a prevalent and formidable malignancy necessitating innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have emerged as crucial regulators in cancer biology. In this study, we comprehensively evaluated ferroptosis levels in BC cells utilizing techniques encompassing lipid peroxidation assessment, transmission electron microscopy, and malondialdehyde (MDA) measurement. Additionally, we probed into the mechanistic intricacies by which circRNAs govern BC, employing RNA pull-down, RNA immunoprecipitation (RIP), and immunoprecipitation (IP) assays. Our investigation unveiled circSIRT5, which displayed significant downregulation in BC. Notably, circSIRT5 emerged as a promising prognostic marker, with diminished expression correlating with unfavorable clinical outcomes. Functionally, circSIRT5 was identified as an inhibitor of BC progression both in vitro and in vivo. Mechanistically, circSIRT5 exerted its tumor-suppressive activities through the formation of a ternary complex involving circSIRT5, SYVN1, and PHGDH. This complex enhanced the ubiquitination and subsequent degradation of PHGDH, ultimately promoting ferroptosis in BC cells. This ferroptotic process contributed significantly to the inhibition of tumor growth and metastasis in BC. In addition, FUS was found to accelerate the biogenesis of circSIRT5 in BC. These findings provide valuable insights into the pivotal role of circSIRT5 in BC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target for this malignancy.

Cannabidiol Modulation of Nicotine‐Induced Toxicity: Assessing Effects on Behavior, Brain‐Derived Neurotrophic Factor, and Oxidative Stress in C57BL/6 Male Mice

ABSTRACTHigh doses of nicotine administered to rodents serve as a model for studying anxiety and test compounds' potential anxiolytic effects. At these doses, anxiety in rodents is accompanied by disruption of brain‐derived neurotrophic factor (BDNF). The endocannabinoids and nicotine modulate several central nervous system processes via their specific receptors, impacting locomotion, anxiety, memory, nociception, and reward. Cannabidiol (CBD), an active ingredient of Cannabis sativa L., is devoid of psychoactive actions and has gained attention for its anxiolytic, antioxidant, and anti‐inflammatory properties, among others. This work aims to examine the potential anxiety‐reducing properties of CBD in a well‐established experimental mouse model of anxiety‐like behavior induced by high doses of nicotine on male C57BL/6 mice. In this context, the open‐field behavioral test was specially conducted to assess CBD's effects on anxiety‐like behavior and locomotion. Brain neuronal plasticity, modulated by BDNF, along with a diverse array of blood's metabolic markers, was examined as a means of evaluating systemic toxicity under various treatments. Finally, oxidative stress was evaluated through the measurement of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), while pro‐inflammatory cytokine assessments were conducted to evaluate redox status and immune system function. Our research suggests that CBD shows potential in reducing anxiety‐like behaviors induced by high doses of nicotine, by mitigating changes in BDNF protein levels in cerebral hemispheres and cerebellum. At the same time, CBD targets specific liver enzymes, maintains tissue's systemic toxicity (i.e., renal, kidney, and pancreatic), balances redox status (SOD, GSH, and MDA), and regulates the secretion of pro‐inflammatory cytokines (TNF‐alpha and IL‐6).