Oxidative Medicine and Cellular Longevity最新文献

[This retracts the article DOI: 10.1155/2022/2235335.].

[This corrects the article DOI: 10.1155/2022/7838583.].

[This retracts the article DOI: 10.1155/2019/1707218.].

Metabolic-endotoxemia, characterized by the translocation of lipopolysaccharide (LPS) from Gram-negative bacteria into the bloodstream, is a key contributor to chronic low-grade inflammation associated with obesity and type 2 diabetes. This condition exacerbates metabolic disruptions by activating Toll-like receptor 4 (TLR4) on macrophages, leading to the release of pro-inflammatory cytokines and subsequent insulin resistance. Eicosapentaenoic acid (EPA; C20:5 (n-3)), an omega-3 polyunsaturated fatty acid, has demonstrated anti-inflammatory and antioxidative properties, but its precise mechanisms of action in mitigating LPS-induced stress remain unclear. This study investigates the pathways through which C20:5 (n-3) alleviates LPS-induced oxidative stress and inflammation in macrophages. C20:5 (n-3) pretreatment significantly reduced LPS-induced inflammatory responses, decreasing IL-1β and IL-6 expression and IL-1β secretion, and lowering the percentage of HLA-DR⁺ macrophages. C20:5 (n-3) also attenuated ER stress, evidenced by reduced expression of ATF4, DDIT3, HSPA5/GRP78, BIP, and CHOP at both gene and protein levels. Oxidative stress was mitigated, as shown by decreased HIF1α expression, reduced ROS levels, and preservation of mitochondrial membrane potential. Importantly, C20:5 (n-3) increased the expression of PPARα and FABP5 while inhibiting NF-κB activation independently of the TLR4-IRF5 pathway. The protective effects of C20:5 (n-3) was abolished by PPARα inhibition with GW9662, indicating that C20:5 (n-3)'s action is PPARα-dependent. This study highlights the modulatory role of C20:5 (n-3) in alleviating LPS-induced oxidative stress and inflammation in macrophages through activation of the FABP5/PPARα/NF-κB axis, independently of TLR4-IRF5 signaling. These findings reveal a novel mechanism for C20:5 (n-3)'s anti-inflammatory effects and suggest that targeting the FABP5/PPARα pathway may offer therapeutic potential for treating metabolic disorders associated with chronic inflammation.

[This retracts the article DOI: 10.1155/2019/9096409.].

Efavirenz (EFV) is a medication widely used for the treatment of HIV-positive patients. Several studies have demonstrated that the prolongate use of EFV can lead to the development of neurological diseases, such as panic syndrome, depression, and anxiety disorders. In this current study, we evaluate whether the ascorbic acid (AA) treatment can prevent anxiety-like behavior and brain oxidative stress induced by EFV treatment in zebrafish. Our data demonstrated that the EFV treatment induces anxiogenic-like behavior and intense lipid peroxidation in the zebrafish brain. The AA treatment was able to prevent both anxiogenic-like behavior and brain oxidative stress elicited by the EFV treatment. Therefore, our data provide robust evidence that the EFV induced anxiety-like behavior in zebrafish via a redox-dependent pathway and that AA treatment can minimize these adverse effects. Taken together, our preclinical study strongly suggests that the use of an AA-enriched diet can minimize the effects of EFV on the central nervous system (CNS) and improve the quality of life for patients undergoing EFV treatment.

Objectives: The aim of this review is to draw attention to key findings from various published studies concerning the effect of methylcobalamin/cyanocobalamin on the immune response of patients diagnosed with pernicious anemia (PA). Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure the accuracy and reliability of the included randomized controlled trials (RCTs) evaluating the impact of vitamin B12, in either natural or synthetic form, on immune function in patients with PA. The protocol was registered with PROSPERO (CRD42024518621). Results: Methylcobalamin/Cyanocobalamin administration in PA patients significantly increased CD3, CD8+, and CD19 cell levels, restoring them toward normal. Natural Killer (NK) cell activity improved, while the CD4/CD8 ratio decreased. These findings indicate a potential enhancement of immune function in PA patients. Conclusion: Significant restoration of CD3, CD8+, and CD19 cell counts was observed in PA patients after vitamin B12 administration, whether in its natural (methylcobalamin) or synthetic (cyanocobalamin) form. Additionally, NK cell activity was improved, and the CD4/CD8 ratio decreased. These findings suggest that methylcobalamin/cyanocobalamin has the potential to significantly enhance immunity in patients with PA. Therefore, we recommend conducting well-designed, large-scale Phase II and Phase III clinical trials with standardized methodologies to validate these findings and provide more robust evidence on the immunomodulatory effect of vitamin B12 in PA patients.

Background: Premature activation of integrin α _IIb β ₃ plays a central role in the induction and development of the platelet storage lesion (PSL) characterized by an exhausted platelet phenotype that affects adhesion and spreading on fibrinogen. Given the role of reactive oxygen species (ROS) in regulating platelet activation per se, we investigated the effects of a ROS scavenger on reducing the functional decline of platelet integrin α _IIb β ₃ during storage. Methods: Platelet-rich plasma-platelet concentrates (PRP-PCs) were either treated with ROS-reducing agents (1 mM N-acetyl-L-cysteine [NAC] or 30 μM NADPH oxidase [NOX] inhibitor, VAS2870) or kept untreated during storage. CD41/CD61 (total integrin α _IIb β ₃) expression and PAC-1 binding (specific to active integrin α _IIb β ₃ conformation) were analyzed by flow cytometry over a 5 day storage period. Molecular changes in integrin β ₃ subunit were evaluated by western blotting. Platelet adhesion/spreading to fibrinogen in the presence of ROS inhibitors was also investigated during storage using fluorescence microscopy. Results: A decrease in the molecular weight of integrin β ₃ subunit was observed during platelet storage, and was significantly reduced by NAC but not VAS2870, suggesting proteolytic cleavage of β ₃ during storage. Further to this, ROS inhibitors decreased integrin activation and increased platelet adhesion to fibrinogen from day 3 of storage, while NAC but not VAS2870 improved platelet spreading. Conclusion: This is the first report of increasing β ₃ cleavage of integrin during storage that was inversely correlated with integrin α _IIb β ₃-mediated platelet function. In this regard, as a generic ROS scavenger, NAC was shown to reduce defects in platelet spreading through inhibition of β ₃ cleavage. This is in contrast to VAS2870 which selectively inhibits cytosolic NOX alone, suggesting that the reduced platelet function observed during storage may be due to cumulative effects of mitochondrial ROS. Taken together, these studies suggest that adding NAC to platelets may significantly preserve optimal integrin α _IIb β ₃ and platelet function during storage. Moreover, as a reversible scavenger, its inhibitory effect can be readily compensated after transfusion.

Monosodium glutamate (MSG) is the most commonly used food additive and has well-known neurotoxic effects. The current study was carried out to assess the underlying mechanisms of the neurotoxicity of MSG on the hippocampus in male rats and examine the protective effect of plasmalogens (Pls) on nuclear factor-B (NF-κB) and p38 MAPK signaling pathways in the hippocampus using behavioral, biochemical, and immunohistochemical methods. Twenty-four male Wistar albino rats were divided into four groups for control or treatment with MSG (2 g/kg body weight) and/or Pls (100 mg/kg body weight). All doses were received orally for 28 days. Results show that plasmalogens ameliorate the levels of glucose, insulin, lipids, oxidative stress markers, antioxidant enzymes, AKT, and neurochemical markers. It also reduces the level of the inflammatory markers TNF-α, NF-κB, and p38 mitogen-activated protein kinase (MAPK). Histological and immunohistochemical alterations in hippocampal tissues were found to be augmented postexposure to Pls, suggesting that Pls have a potent ameliorative effect. We conclude that Pls exert anti-inflammatory, antioxidant, and antiapoptotic effects and counteract MSG-induced neurotoxicity by altering the NF-κB and p38 MAPK signaling pathways.

Background: Aging is characterized by the progressive decline of physiological functions and is associated with an increasing risk for developing multiple age-related diseases. UDP-glucuronosyltransferase (UGT)1A enzymes detoxify a variety of endo- and xenobiotic reactive metabolites, thereby acting as indirect antioxidants. A common genetic UGT1A haplotype was shown to affect redox balance in humanized transgenic (htg) UGT1A mice. Since oxidative stress is a main activator of cellular senescence, we aimed to investigate the role of genetic UGT1A variants in the process of aging. Methods: HtgUGT1A-WT and htgUGT1A-SNP mice were harvested at the age of either 12 weeks (young) or 18 months (aged). The effect of aging was examined by analyzing UGT1A expression and activity, expression of senescence markers, and senescence-associated secretory phenotype (SASP) factors, as well as blood counts, serum parameter, and histological staining. Results: In comparison to aged htgUGT1A-WT mice, hepatic UGT1A mRNA and protein expression as well as UGT activity were significantly reduced in aged htgUGT1A-SNP mice. Moreover, elderly htgUGT1A-SNP mice exhibited increased levels of oxidative stress, senescence markers, SASP factors, and peripheral leukocyte counts compared to the respective htgUGT1A-WT mice. Consistent with these findings, we observed higher amounts of collagen and amyloid fibrils as well as an elevated senescence-associated β-galactosidase (SA-β-gal) activity in histological sections of the liver obtained from aged htgUGT1A-SNP mice. Conclusion: Our data suggest an accelerated aging process caused by a common UGT1A haplotype. Moreover, elderly individuals carrying the UGT1A haplotype might exhibit an altered metabolism of drugs, which could necessitate dose adjustments.