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PloS One 2024Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally...
Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally occurring naphthoquinone in J. mandshurica, exhibits significant cytotoxic activity against various cancer cell lines. However, whether the anticancer activity of juglone is associated with oxidative stress remains unexplored. In this study, mouse Lewis lung cancer (LLC) and human non-small cell lung cancer A549 cells were used to explore the anticancer mechanisms of juglone. Juglone inhibited LLC and A549 cells viability, with IC50 values of 10.78 μM and 9.47 μM, respectively, for 24 h, and substantially suppressed the migration and invasion of these two lung cancer cells. Additionally, juglone arrested the cell cycle, induced apoptosis, increased the cleavage of caspase 3 and the protein expression of Bax and Cyt c, and decreased the protein expression of Bcl-2 and caspase-3. Furthermore, juglone treatment considerably increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, but suppressed glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD) activities. It also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which was attenuated by 1,3-diCQA (an activator of PI3K/Akt). Moreover, N-acetylcysteine (a ROS scavenger) partially reversed the positive effects of juglone in terms of migration, invasion, ROS production, apoptosis, and PI3K/Akt pathway-associated protein expression. Finally, in tumor-bearing nude mouse models, juglone inhibited tumor growth without any apparent toxicity and significantly induced apoptosis in NSCLC cells. Collectively, our findings suggest that juglone triggers apoptosis via the ROS-mediated PI3K/Akt pathway. Therefore, juglone may serve as a potential therapeutic agent for the treatment of NSCLC.
Topics: Naphthoquinones; Carcinoma, Non-Small-Cell Lung; Reactive Oxygen Species; Humans; Animals; Apoptosis; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Lung Neoplasms; Mice; Signal Transduction; A549 Cells; Cell Movement; Carcinoma, Lewis Lung; Cell Line, Tumor
PubMed: 38814975
DOI: 10.1371/journal.pone.0299921 -
Heliyon May 2024In this novel research, S-scheme AgCrO/g-CN heterojunctions were generated by sonochemical hybridization of different compositions of AgCrO nanoparticles...
In this novel research, S-scheme AgCrO/g-CN heterojunctions were generated by sonochemical hybridization of different compositions of AgCrO nanoparticles [E = +2.21 eV] and g-CN sheets [E = -1.3 eV] for destructing RhB dye under artificial solar radiation. The as-synthesized nanocomposites were subjected to X-ray diffraction [XRD], diffuse reflectance spectrum [DRS], X-ray photoelectron spectroscopy [XPS], N-adsorption-desorption isotherm, photoluminescence [PL] and high resolution transmission electron microscope [HRTEM] analysis to explore the interfacial interactions between g-CN sheets and AgCrO nanoparticles. Spherical AgCrO nanoparticles deposited homogeneously on the wrinkles points of g-CN sheets at nearly equidistant from each other facilitating the uniform absorption of solar radiations. The absorbability of solar radiations was enhanced by introducing 20 wt % AgCrO on g-CN sheets. The surface area of g-CN sheets was reduced from 37.5 to 16.4 m/g and PL signal intensity diminished by 80 % implying the successful interfacial interaction between AgCrO nanoparticles and g-CN sheets. The photocatalytic performance of heterojunctions containing 20 % AgCrO and 80 % g-CN destructed 96 % of RhB dye compared with 60 and 33 % removal on the surface of pristine g-CN sheets and AgCrO, respectively. Benzoquinone and ammonium oxalate are strongly scavenged the dye decomposition revealing the strong influence of valence band holes of AgCrO and superoxide radicals in destructing RhB dye under solar radiations. S-scheme charge transportation mechanism was suggested rather than type II heterojunction on the light of scavenger trapping experiments results and PL spectrum of terephthalic acid. Overall, this research work illustrated the manipulation of novel S-scheme heterojunction with efficient redox power for destructing various organic pollutants persisted in water resources.
PubMed: 38813157
DOI: 10.1016/j.heliyon.2024.e31221 -
Turkish Journal of Medical Sciences 2023Propofol is a positive allosteric modulator of GABAA receptor (GABAAR) and has potent antioxidant activity. The aim of this study was to investigate the effect of...
Propofol mitigates brain injury and oxidative stress, and enhances GABAA receptor α1 subunit expression in a rat model of lithium chloride-pilocarpine induced status epilepticus.
BACKGROUND/AIM
Propofol is a positive allosteric modulator of GABAA receptor (GABAAR) and has potent antioxidant activity. The aim of this study was to investigate the effect of propofol on damage to the cerebral cortex and hippocampus in a lithium chloride (LiCl)-pilocarpine animal model of status epilepticus (SE).
MATERIALS AND METHODS
Adult male Sprague Dawley rats were injected with LiCl-pilocarpine to induce SE. They were then randomized and injected 30 min later with vehicle saline (SE+saline), propofol (SE+PPF, 50 mg/kg), Diazepam (SE+DZP, 10 mg/kg), Scopolamine (SE+SCOP, 10 mg/kg), or MK-801 (SE+MK-801, 2 mg/kg). Another group of rats received saline only and served as the naïve control (BLK). The levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in the serum, cortex and hippocampus were analyzed 2 and 24 h posttreatment. The degree of tissue damage in the cortex and hippocampus of individual rats was assessed 24 h posttreatment, together with expression of the GABAAR α1 subunit.
RESULTS
The propofol group showed reduced levels of tissue damage in the cerebral cortex and hippocampus, decreased levels of MDA, and increased levels of GSH compared to the SE+saline group. No changes in SOD level were observed in serum and tissue samples from the cortex and hippocampus of SE+saline rats. Immunohistochemistry and Western blot assays showed that propofol treatment significantly increased the expression of GABAR α1 subunit in the cortical and hippocampal tissues of SE rats.
CONCLUSION
Propofol treatment protected against SE-induced tissue injury in the cortex and hippocampus of rats. This was due at least in part to its antioxidant activity and to its induction of GABAAR α1 subunit expression in the brain.
Topics: Animals; Propofol; Receptors, GABA-A; Status Epilepticus; Pilocarpine; Male; Rats, Sprague-Dawley; Lithium Chloride; Oxidative Stress; Rats; Disease Models, Animal; Hippocampus; Brain Injuries; Malondialdehyde; Cerebral Cortex
PubMed: 38813010
DOI: 10.55730/1300-0144.5670 -
Frontiers in Bioscience (Landmark... May 2024Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth...
BACKGROUND
Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth of evidence suggests that, along with canonical enzymes of reactive oxygen species regulation, human blood contains antibodies with peroxidase, superoxide dismutase, and catalase activities. Here we show that the catalase activity of IgGs and their κκ-IgG, λλ-IgG, and κλ-IgG subfractions of HIV-infected individuals is significantly different compared to the healthy donors.
METHODS
Protein G-Sepharose sorbent was used to resolve IgG from blood of healthy donors and HIV-infected patients by affinity chromatography. Subfractions of κκ-IgG, λλ-IgG, and κλ-IgG were separated from IgGs samples of each group by affinity chromatography on sorbents containing immobilized antibodies to κ or λ light human chains. The IgG catalase activity level was measured spectrophotometrically by evaluating the decrease in optical density (A240) due to hydrogen peroxide decomposition.
RESULTS
The relative catalase activity of antibodies from HIV-infected patients ( = (1.41 ± 0.92) × 103 min-1, 95% CI: [1.01-1.81]) was statistically significant, 1.6 times higher ( = 0.014) compared to apparently healthy donors ((0.86 ± 0.49) × 103, 95% CI: [0.69-1.03]). The activity level of κκ-IgG HIV-infected patients ((0.44 ± 0.04) × 103 min-1) was 1.4 times higher than that of λλ-IgGs ((0.31 ± 0.025) × 103 min-1); the opposite was observed for κκ-IgGs from apparently healthy donors, which activity ((0.17 ± 0.015) × 103 min-1) was 3.1 times lower compared to λλ-IgGs ((0.53 ± 0.045) × 103 min-1).
CONCLUSIONS
Thus, the data obtained may indicate that IgG with increased catalase activity may prevent harmful processes arising from oxidative stress in HIV-infected patients, acting as an additional natural molecular mechanism of regulation of hydrogen peroxide level.
Topics: Humans; Catalase; Immunoglobulin G; HIV Infections; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Adult; Case-Control Studies; Male; Female; Chromatography, Affinity; Oxidative Stress; Middle Aged
PubMed: 38812328
DOI: 10.31083/j.fbl2905191 -
Translational Neurodegeneration May 2024Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, resulting in global health burden and... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, resulting in global health burden and limited post-diagnosis life expectancy. Although primarily sporadic, familial ALS (fALS) cases suggest a genetic basis. This review focuses on SOD1, the first gene found to be associated with fALS, which has been more recently confirmed by genome sequencing. While informative, databases such as ALSoD and STRENGTH exhibit regional biases. Through a systematic global examination of SOD1 mutations from 1993 to 2023, we found different geographic distributions and clinical presentations. Even though different SOD1 variants are expressed at different protein levels and have different half-lives and dismutase activities, these alterations lead to loss of function that is not consistently correlated with disease severity. Gain of function of toxic aggregates of SOD1 resulting from mutated SOD1 has emerged as one of the key contributors to ALS. Therapeutic interventions specifically targeting toxic gain of function of mutant SOD1, including RNA interference and antibodies, show promise, but a cure remains elusive. This review provides a comprehensive perspective on SOD1-associated ALS and describes molecular features and the complex genetic landscape of SOD1, highlighting its importance in determining diverse clinical manifestations observed in ALS patients and emphasizing the need for personalized therapeutic strategies.
Topics: Amyotrophic Lateral Sclerosis; Humans; Superoxide Dismutase-1; Mutation
PubMed: 38811997
DOI: 10.1186/s40035-024-00416-x -
Diabetology & Metabolic Syndrome May 2024While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively...
Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ-mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats.
BACKGROUND & OBJECTIVE
While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed to assess the renoprotective potentials of methanol (MO) and methylene chloride (MC) fixed oil extracts of purslane seeds in a diabetic nephropathy (DN) model.
METHODS
Purslane seeds were extracted using absolute methanol and methylene chloride, and type-1 diabetes was induced with a single 55 mg/kg dose of Streptozotocin (STZ) dissolved in 100 mmol/L citrate buffer (pH 4.5), and then diabetic animals were received MO, MC, for 42 consecutive days to compare their antidiabetic effect relative to the reference drug "Losartan". Renal functions and DN biomarkers were weekly assessed, and the relative expression of different oxido-inflammatory mediators was quantified in diabetic kidneys by RT-PCR. Data were statistically analyzed using GraphPad Prism 9.0.2.
RESULTS
The oral administration of MO and MC extracts (250 mg/kg/day) significantly ameliorated the body weight loss (P < 0.0001 / each), fasting blood glucose levels (FBG) (P < 0.0001 / each), urine volume (P < 0.0001 / each), as well as serum creatinine (P < 0.0001 / each), uric acid (P = 0.0022, 0.0052), and blood urea nitrogen (BUN) (P = 0.0265, 0.0338); respectively, compared with the untreated diabetic rats. In addition, both extracts restored the effectuality of antioxidative machinery in diabetic kidneys as indicated by a significant reduction of ROS accumulation and lipid peroxidation; higher GSH content, and promoted activity of glutathione reductase and superoxide dismutase antioxidant enzymes (P < 0.0001 / each). Histologically, both extracts alleviated the DN-structural alterations including the glomerular congestion and tubular degeneration, with MC-treated kidneys showing near to normal architecture. The transcription profiles of all treated kidneys revealed a significantly downregulated expression of TNF-α, IL-6, Keap1 and NF-κB genes, concomitant with a significant upregulation of SDF-1, IL-10, Nrf2, HO-1, and PPARγ gene expression (P < 0.0001 / all).
CONCLUSION
These findings highlight the remarkable DN-prophylactic potentials of purslane extracts mediated by neutralizing the hyperglycemia-induced ROS accumulation, and circumventing the downstream inflammatory cascades, surpassing the reference angiotensin receptor blocker; i.e. Losartan.
PubMed: 38811991
DOI: 10.1186/s13098-024-01330-y -
BMC Plant Biology May 2024Ring rot, caused by Botryosphaeria dothidea, is an important fungal disease of pear fruit during postharvest storage. Melatonin, as a plant growth regulator, plays an...
Ring rot, caused by Botryosphaeria dothidea, is an important fungal disease of pear fruit during postharvest storage. Melatonin, as a plant growth regulator, plays an important role in enhancing the stress resistance of pear fruits. It enhances the resistance of pear fruits to ring rot by enhancing their antioxidant capacity. However, the underlying mechanism remains unclear. In this study, we examined the effect of melatonin on the growth of B. dothidea. Results showed that melatonin did not limit the growth of B. dothidea during in vitro culture. However, metabolomics and transcriptomics analyses of 'Whangkeumbae' pear (Pyrus pyrifolia) revealed that melatonin increased the activity of antioxidant enzymes, including peroxidase (POD), superoxide dismutase (SOD), and polyphenol oxidase (PPO), in the fruit and activated the phenylpropanoid metabolic pathway to improve fruit resistance. Furthermore, melatonin treatment significantly increased the contents of jasmonic acid and phlorizin in pear fruit, both of which could improve disease resistance. Jasmonic acid regulates melatonin synthesis and can also promote phlorizin synthesis, ultimately improving the resistance of pear fruit to ring rot. In summary, the interaction between melatonin and jasmonic acid and phlorizin enhances the antioxidant defense response and phenylpropanoid metabolism pathway of pear fruit, thereby enhancing the resistance of pear fruit to ring rot disease. Our results provide new insights into the application of melatonin in the resistance to pear fruit ring rot.
Topics: Pyrus; Cyclopentanes; Oxylipins; Ascomycota; Melatonin; Disease Resistance; Plant Diseases; Fruit; Phlorhizin; Gene Expression Regulation, Plant; Antioxidants; Plant Growth Regulators
PubMed: 38811892
DOI: 10.1186/s12870-024-05187-1 -
Redox Biology May 2024
Corrigendum to "A model of mitochondrial superoxide production during ischaemia-reperfusion injury for therapeutic development and mechanistic understanding" [Redox Biol. 72 (2024) 103161].
PubMed: 38811270
DOI: 10.1016/j.redox.2024.103210 -
Bioactive Materials Sep 2024Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even...
Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in radiation and chemotherapy medicine, but the short half-life limits its bioavailability and clinical applications, remaining as a great challenge to be addressed. DNA-assembled nanostructures especially the tetrahedral framework nucleic acids (tFNAs) are promising nanocarriers with preeminent biosafety, low biotoxicity, and high transport efficiency. The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity. We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection (tFNAs@AMF, also termed nanosuit). By establishing the mice models of accidental total body irradiation (TBI) and radiotherapy model of Lewis lung cancer, we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress. In the accidental total body irradiation (TBI) mice model, the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents, and functional recovery of hematopoietic system, reducing IR-induced pathological damages of multi-organ and safeguarding mice from lethal radiation. More importantly, the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer. Based on a conveniently available DNA tetrahedron-based nanocarrier, this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs. Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.
PubMed: 38808157
DOI: 10.1016/j.bioactmat.2024.05.017 -
Clinical Interventions in Aging 2024This study investigated the effect of consumption of table eggs enriched with n-3 polyunsaturated fatty acids (n-3 PUFA), lutein, vitamin E and selenium on microvascular... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This study investigated the effect of consumption of table eggs enriched with n-3 polyunsaturated fatty acids (n-3 PUFA), lutein, vitamin E and selenium on microvascular function, oxidative stress and inflammatory mediators in patients after acute coronary syndrome (ACS).
PATIENTS AND METHODS
In a prospective, randomized, interventional, double-blind clinical trial, ACS patients were assigned to either the Nutri4 (N=15, mean age: 57.2 ± 9.2 years), or the Control group (N=13; mean age 56.8 ± 9.6 years). The Nutri4 group consumed three enriched hen eggs daily for three weeks, providing approximately 1.785 mg of vitamin E, 0.330 mg of lutein, 0.054 mg of selenium and 438 mg of n-3 PUFAs. Biochemical parameters, including serum lipids, liver enzymes, nutrient concentrations, serum antioxidant enzyme activity (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)), and markers of oxidative stress (thiobarbituric acid reactive substances (TBARS) and ferric reducing ability (FRAP)), were assessed before and after the dietary interventions. Additionally, arterial blood pressure, heart rate, body composition, fluid status, anthropometric measurements, and skin microvascular blood flow responses to various stimuli (postocclusive reactive hyperemia (PORH), acetylcholine- (Ach ID), and sodium nitroprusside- (SNP ID)) were measured using laser Doppler flowmetry (LDF) throughout the study.
RESULTS
The intake of Nutri4 eggs led to a significant reduction in LDL cholesterol levels, while the levels of total cholesterol remained within the established reference values. Consuming Nutri4 eggs resulted in a 12.7% increase in serum vitamin E levels, an 8.6% increase in selenium levels, and demonstrated a favorable impact on microvascular reactivity, as evidenced by markedly improved PORH and ACh ID. Nutri4 eggs exerted a significant influence on the activity of GPx and SOD, with no observed changes in TBARS or FRAP values.
CONCLUSION
The consumption of Nutri4 eggs positively influenced microvascular function in individuals with ACS, without eliciting adverse effects on oxidative stress.
Topics: Humans; Middle Aged; Eggs; Oxidative Stress; Female; Acute Coronary Syndrome; Male; Double-Blind Method; Prospective Studies; Vitamin E; Animals; Fatty Acids, Omega-3; Aged; Lutein; Selenium; Antioxidants; Endothelium, Vascular; Superoxide Dismutase; Chickens; Food, Fortified
PubMed: 38807636
DOI: 10.2147/CIA.S461821