Oxidative Medicine and Cellular Longevity最新文献

{"title":"The Effects of Silymarin on Calcium Chloride-Induced Arrhythmia in Male Rat.","authors":"Fereshteh Toghroli, Mohammad Foad Noorbakhsh, Javad Sajedianfard","doi":"10.1155/2024/6720138","DOIUrl":"10.1155/2024/6720138","url":null,"abstract":"<p><p>Antioxidants play an important role in protecting cardiac arrhythmias. Silymarin, strong antioxidant, is effective in reducing the complications caused by arrhythmias. This study was conducted to determine the effect of silymarin on the prevention and treatment of calcium chloride-induced arrhythmia. In total, 48 male rats were randomly divided into six groups: the first control group for acute administration received intravenous injection of 0.2 mL of dimethylsulfoxide, a cosolvent, immediately after induction of arrhythmia; the second control group for chronic administration, daily gavage of dimethylsulfoxide for 2 weeks before induction of arrhythmia; acute silymarin group, 100 mg/kg intravenous, immediately after the occurrence of arrhythmia; chronic silymarin group, daily gavage of 50 mg/kg for 2 weeks before induction of arrhythmia; amiodarone standard treatment, 5 mg/kg intravenous, immediately after induction of arrhythmia; and quinidine standard treatment, 10 mg/kg intravenous, immediately after induction of arrhythmia. Calcium chloride (140 mg/kg, i.v.) was used to induce arrhythmia. Electrocardiogram was recorded and monitored by PowerLab™ system. The incidence rates of premature ventricular beat (PVB), ventricular tachycardia (VT), and ventricular fibrillation (VF) were calculated. The antiarrhythmic effect of silymarin was observed with a significant decrease in the incidence of premature ventricular beat (22.56 ± 1.04%, <i>P</i> < 0.001), ventricular tachycardia (34.150 ± 1.59%, <i>P</i> < 0.001), and ventricular fibrillation (24.31 ± 1.02%, <i>P</i> < 0.001) compared with the control group (100%). These effects were comparable to antiarrhythmic drugs such as quinidine (29.23% ± 1.24%, 52.23% ± 1.13%, 66.31% ± 1.81%) and amiodarone (22.91% ± .72%, 41.09% ± 1.66%, 61.59% ± 1.11%). Silymarin exerts a potent antioxidant effect, thereby mitigating the risk of VT, VF, and PVC.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Effects of <i>Nigella sativa</i> Oil and Whole Seeds on STZ-Induced Diabetic Rats: A Biochemical and Immunohistochemical Study.","authors":"Naif AlSuhaymi","doi":"10.1155/2024/5594090","DOIUrl":"10.1155/2024/5594090","url":null,"abstract":"<p><strong>Background: </strong>Type II diabetes mellitus (DM) is an increasing health problem that has negative impacts on patients and healthcare systems, worldwide. The development of new therapies with better efficacy, fewer side effects, and lower prices are urgently needed to treat this disease.</p><p><strong>Aim: </strong>To evaluate and compare the therapeutic effects of <i>Nigella sativa</i> (<i>N. sativa</i>) seed and oil on the biochemical parameters and regeneration of pancreatic islets (or islets of Langerhans) of streptozotocin (STZ)-induced diabetic rats.</p><p><strong>Materials and methods: </strong>The diabetic rat model was prepared by administering a single dose of STZ (35 mg/kg body weight). The whole seed or the oil of <i>N. sativa</i> was administered to the diabetic and control groups for a period of 28 days, but not to the negative and STZ controls. Serum blood glucose, liver enzymes, lipid profile, and renal function tests (uric acid, albumin, total protein, urea, and creatinine) were measured in all groups. After the rats were euthanized, their pancreases were extracted, and then sectioned and fixed on slides in preparation before staining with H&E stain and immunohistochemical study.</p><p><strong>Results: </strong>Treatment of STZ-diabetic rats with <i>N. sativa</i> seeds or oil significantly improved their serum glucose levels, lipid profiles, and liver and renal functions as well as preserved the integrity of pancreatic <i>β</i> cells.</p><p><strong>Conclusion: </strong><i>N. sativa</i> seeds and oil demonstrate significant therapeutic improvement effects on DM and its related complications including effective protection of islets of Langerhans. The therapeutic benefits of <i>N. sativa</i> seeds and oil on DM and its related complications are comparable.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin Increases Growth Performance and Decreases Incidence of Diarrhea and Mechanism of Action in Weaned Piglets.","authors":"Yanjun Mao, Qinglin Yang, Junhong Liu, Yuxin Fu, Shuaishuai Zhou, Jiayan Liu, Linlin Ying, Yao Li","doi":"10.1155/2024/5632260","DOIUrl":"10.1155/2024/5632260","url":null,"abstract":"<p><p>This study aimed to investigate the mechanism of quercetin increasing growth performance and decreasing incidence of diarrhea in weaned piglets. Forty-eight Duroc × Landrace × Large White weaned piglets with similar body weight (7.48 ± 0.20 kg, 28 days of age) were randomly divided into four treatments (control, 250 mg/kg quercetin, 500 mg/kg quercetin, and 750 mg/kg quercetin treatments) and fed with basal diet or experimental diet supplemented with quercetin. Performance, diarrhea rate and index, and content of serum anti-inflammatory factors were determined and calculated in weaned piglets; colonic flora and signaling pathways related to anti-inflammation were measured using 16S rDNA sequencing and RNA-seq, respectively. The results showed that compared with control, feed-to-gain ratio and content of serum interferon gamma (IFN-<i>γ</i>) were significantly decreased in the 500 and 750 mg/kg quercetin treatments (<i>P</i> < 0.05); quercetin significantly decreased diarrhea rate and diarrhea index (<i>P</i> < 0.05) and significantly increased the content of serum transforming growth factor (TGF-<i>β</i>) in weaned piglets (<i>P</i> < 0.05); the content of serum NF-<i>κ</i>B was significantly decreased in the 750 mg/kg quercetin treatment (<i>P</i> < 0.05); moreover, quercetin significantly increased diversity of colonic flora (<i>P</i> < 0.05), and at the phylum level, the relative abundance of Actinobacteria in the 500 and 750 mg/kg treatments was significantly increased (<i>P</i> < 0.05), and the relative abundance of Proteobacteria in the three quercetin treatments were significantly decreased (<i>P</i> < 0.05) in the colon of weaned piglets; at the genus level, the relative abundance of <i>Clostridium-sensu-stricto-1</i>, <i>Turicibacter</i>, <i>unclassified_f_Lachnospiraceae</i>, <i>Phascolarctobacterium</i>, and <i>Family_XIII _AD3011_group</i> was significantly increased (<i>P</i> < 0.05); the relative abundance of <i>Subdollgranulum</i> and <i>Blautia</i> was significantly decreased in the 500 and 750 mg/kg treatments (<i>P</i> < 0.05); the relative abundance of <i>Eschericha-Shigella</i>, <i>Terrisporobacter</i>, and <i>Eubacterium-coprostanoligenes</i> was significantly increased (<i>P</i> < 0.05); the relative abundance of <i>Streptocococcus</i>, <i>Sarcina</i>, <i>Staphylococcus</i>, and <i>Ruminococcaceae_UCG-008</i> was significantly decreased in the three quercetin treatments (<i>P</i> < 0.05); the relative abundance of <i>Ruminococcaceae_UCG_014</i> was significantly increased in the 250 mg/kg quercetin treatment in the colon of weaned piglets (<i>P</i> < 0.05). The results of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differentially expressed genes (DEGs) from the quercetin treatments were significantly enriched in nuclear transcription factor-<i>κ</i>B (NF-<i>κ</i>B) signal pathway (<i>P</i> < 0.05); mRNA expression of tumor necrosis factor-<i>α</i> (TNF-<i>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric Analysis of the Role of Occludin in the Pathogenesis of Stroke.","authors":"Zhanylsyn U Urasheva, Gulnar B Kabdrakhmanova, Aigul P Yermagambetova, Aigerim B Utegenova, Nazgul A Seitmaganbetova, Ondassyn M Aliyev, Saulesh S Kurmangaliyeva, Nazym K Kenzhina, Yergen Z Kurmambayev, Alima A Khamidulla","doi":"10.1155/2024/2121733","DOIUrl":"10.1155/2024/2121733","url":null,"abstract":"<p><p>Over the past decade, there has been a notable surge in research dedicated to unraveling the intricate role of tight junction proteins in blood-brain barrier (BBB) damage associated with ischemic stroke. This bibliometric analysis explores the expansive landscape of occludin research, a key tight junction protein, during the years 2000-2023, shedding light on the global scientific contributions, collaborations, and emerging trends in this critical area of stroke pathogenesis. China and the United States emerge as significant contributors, underscoring their prominence in advancing our understanding of tight junction proteins. Occludin, identified as a linchpin in regulating BBB integrity, proves to be a pivotal player, with implications extending to the diagnosis of hemorrhagic transformation in ischemic stroke. This study identifies occludin as a potential biomarker, offering promise for early diagnosis and paving the way for novel diagnostic strategies. The analysis highlights the necessity for a more comprehensive exploration of tight junction proteins, including occludin and claudin-5, particularly in the context of acute cerebral ischemia. The unique healthcare landscape in Kazakhstan adds urgency to the call for further scientific research in this region, emphasizing the need for tailored investigations to address specific regional challenges. This comprehensive overview not only delineates the current state of occludin research but also signals the direction for future investigations. The identified knowledge gaps and emerging trends provide a roadmap for researchers and policymakers alike, with implications for both scientific discourse and clinical practice. Moving forward, a deeper understanding of tight junction proteins, informed by the insights gleaned from this study, holds the potential to shape targeted therapeutic interventions and diagnostic strategies, ultimately contributing to advancements in global stroke care.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Aloe vera</i> Leaf Extract Reduced BBB Permeability and Improved Neurological Results after Traumatic Brain Injury: The Role of Oxidative Stress.","authors":"Mohammad Khaksari, Marzieh Shahryari, Alireza Raji-Amirhasani, Zahra Soltani, Bahram Bibak, Zakieh Keshavarzi, Farzaneh Shakeri","doi":"10.1155/2024/5586814","DOIUrl":"10.1155/2024/5586814","url":null,"abstract":"<p><strong>Introduction: </strong>Recognizing the importance of medicinal plants and the absence of specific medications for traumatic brain injury (TBI) treatment, this study was conducted to evaluate the effects of an aqueous extract of <i>Aloe vera</i> on oxidative stress, blood-brain barrier (BBB) permeability, and neurological scores following TBI.</p><p><strong>Materials and methods: </strong>Adult male rats were categorized into five groups: sham, TBI, vehicle, low-dose <i>Aloe vera</i> (LA), and high-dose <i>Aloe vera</i> (HA). We induced diffuse TBI using the Marmaro model and administered the aqueous <i>Aloe vera</i> leaf extract, as well as vehicle, via intraperitoneal injection half an hour after TBI. Neurological outcomes were assessed both before and several hours after TBI. Additionally, oxidative stress factors were measured 24 hr after TBI, and Evans blue content (a BBB permeability index) was determined 5 hr after TBI in both serum and brain.</p><p><strong>Results: </strong>Both LA and HA reduced the increase in BBB permeability after TBI, with HA having a more pronounced effect than LA. Both <i>Aloe vera</i> doses decreased brain MDA levels, increased brain TAC, and lowered both serum and brain PC levels. The impact of <i>Aloe vera</i> on brain oxidative parameters was more significant than on serum. HA also counteracted the declining effects of TBI on neurological outcomes at 4 and 24 hr post-TBI.</p><p><strong>Conclusion: </strong>This study suggests that <i>Aloe vera</i> extract may reduce BBB permeability and improve neurological outcomes after TBI by decreasing oxidative factors and increasing antioxidant factors.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the Proteome of the Circle of Willis during Aging Reveal Signatures of Vascular Disease.","authors":"Vikram Subramanian, Denise Juhr, Lydia S Johnson, Justin B Yem, Piero Giansanti, Isabella M Grumbach","doi":"10.1155/2024/4887877","DOIUrl":"10.1155/2024/4887877","url":null,"abstract":"<p><p>Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Vitamins in Spinal Cord Injury: Mechanisms and Benefits.","authors":"Fatemeh Abbaszadeh, Pegah Javadpour, Mohammad Mehdi Mousavi Nasab, Masoumeh Jorjani","doi":"10.1155/2024/4293391","DOIUrl":"https://doi.org/10.1155/2024/4293391","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a common neurological disease worldwide, often resulting in a substantial decrease in quality of life, disability, and in severe cases, even death. Unfortunately, there is currently no effective treatment for this disease. Nevertheless, current basic and clinical evidence suggests that vitamins, with their antioxidant properties and biological functions, may play a valuable role in improving the quality of life for individuals with SCI. They can promote overall health and facilitate the healing process. In this review, we discuss the mechanisms and therapeutic potential of vitamins in the treatment of SCI.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of Cannabispirenone A against NMDA-Induced Excitotoxicity in Differentiated N2a Cells","authors":"Sonia Thapa, Yedukondalu Nalli, Ajeet Singh, Shashank Kr. Singh, Asif Ali","doi":"10.1155/2024/3530499","DOIUrl":"https://doi.org/10.1155/2024/3530499","url":null,"abstract":"The endocannabinoid system is found throughout the central nervous system, and its cannabinoids receptor 1 is critical in preventing neurotoxicity caused by N-methyl-D-aspartate receptor activation (NMDARs). The activity of NMDARs places demands on endogenous cannabinoids to regulate their calcium currents. Endocannabinoids keep NMDAR activity within safe limits, protecting neural cells from excitotoxicity. Cannabinoids are remembered to deliver this outcome by repressing presynaptic glutamate discharge or obstructing postsynaptic NMDAR-managed flagging pathways. The endocannabinoid system must exert a negative influence proportional to the strength of NMDAR signaling for such control to be effective. The goal of this paper is to draw the attention towards the neuroprotective mechanism of constituents of <i>Cannabis sativa</i> against NMDA-induced excitotoxic result. Phytochemical investigation of the cannabis flowers led to the isolation of nine secondary metabolites. A spiro-compound, Cannabispirenone A, which on treatment of the cells prior to NMDA exposure significantly increases cell survival while decreasing ROS production, lipid peroxidation, and intracellular calcium. Our findings showed that this compound showed neuroprotection against NMDA-induced excitotoxic insult, has antioxidative properties, and increased cannabinoid receptor 1 expression, which may be involved in the signaling pathway for this neuroprotection.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141192270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abatacept: A Promising Repurposed Solution for Myocardial Infarction-Induced Inflammation in Rat Models","authors":"Vipin Kumar Verma, Ekta Mutneja, Salma Malik, Anil Kumar Sahu, Vaishali Prajapati, Priya Bhardwaj, Ruma Ray, Tapas Chandra Nag, Jagriti Bhatia, Dharamvir Singh Arya","doi":"10.1155/2024/3534104","DOIUrl":"https://doi.org/10.1155/2024/3534104","url":null,"abstract":"Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (<i>n</i> = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT <i>perse</i>. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant–antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140116735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACA-28, an ERK MAPK Signaling Modulator, Exerts Anticancer Activity through ROS Induction in Melanoma and Pancreatic Cancer Cells","authors":"Teruaki Takasaki, Yasuyuki Hamabe, Kenta Touchi, Golam Iftakhar Khandakar, Takeshi Ueda, Hitoshi Okada, Kazuko Sakai, Kazuto Nishio, Genzoh Tanabe, Reiko Sugiura","doi":"10.1155/2024/7683793","DOIUrl":"https://doi.org/10.1155/2024/7683793","url":null,"abstract":"The extracellular signal-regulated kinase (ERK) MAPK pathway is dysregulated in various human cancers and is considered an attractive therapeutic target for cancer. Therefore, several inhibitors of this pathway are being developed, and some are already used in the clinic. We have previously identified an anticancer compound, ACA-28, with a unique property to preferentially induce ERK-dependent apoptosis in melanoma cells. To comprehensively understand the biological cellular impact induced by ACA-28, we performed a global gene expression analysis of human melanoma SK-MEL-28 cells exposed to ACA-28 using a DNA microarray. The transcriptome analysis identified nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcription factor that combats oxidative stress, as the most upregulated genetic pathway after ACA-28 treatment. Consistently, ACA-28 showed properties to increase the levels of reactive oxygen species (ROS) as well as Nrf2 protein, which is normally repressed by proteasomal degradation and activated in response to oxidative stresses. Furthermore, the ROS scavenger N-acetyl cysteine significantly attenuated the anticancer activity of ACA-28. Thus, ACA-28 activates Nrf2 signaling and exerts anticancer activity partly via its ROS-stimulating property. Interestingly, human A549 cancer cells with constitutively high levels of Nrf2 protein showed resistance to ACA-28, as compared with SK-MEL-28. Transient overexpression of Nrf2 also increased the resistance of cells to ACA-28, while knockdown of Nrf2 exerted the opposite effect. Thus, upregulation of Nrf2 signaling protects cancer cells from ACA-28-mediated cell death. Notably, the Nrf2 inhibitor ML385 substantially enhanced the cell death-inducing property of ACA-28 in pancreatic cancer cells, T3M4 and PANC-1. Our data suggest that Nrf2 plays a key role in determining cancer cell susceptibility to ACA-28 and provides a novel strategy for cancer therapy to combine the Nrf2 inhibitor and ACA-28.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}