Pub Date : 2024-08-20eCollection Date: 2024-01-01DOI: 10.1155/2024/6612009
Marawan A Elbaset, Sherif M Afifi, Tuba Esatbeyoglu, Sahar S Abdelrahman, Dalia O Saleh
Cisplatin-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cisplatin chemotherapy used in cancer treatment. This study explored the neuroprotective effects of Trimetazidine (TRI) against CIPN by preserving nerve integrity, reducing neuro-oxidative stress, and alleviating neuroinflammation. Using a rat model of CIPN, we evaluated TRI's impact on motor coordination, pain sensitivity, and peripheral nerve histopathology. Also, its effects on neuro-oxidative stress and neuroinflammatory markers were assessed. The findings showed that rats with CIPN had worse motor coordination and increased sensitivity to pain but that these symptoms were alleviated by TRI therapy in a dose-dependent way. Nerve conduction velocities were normalized, and expression of genes involved in neuropathy signaling was suppressed after TRI therapy. Antioxidant benefits were also shown in TRI, with oxidative damage being reduced and the cellular energy balance being restored. By inhibiting the production of inflammatory markers, it also demonstrated anti-inflammatory properties. Histopathological examination revealed that TRI, especially when administered at a higher dose, inhibited the degeneration and demyelination of nerve fibers. The anti-inflammatory properties of TRI in the sciatic nerves were further shown by the fact that its administration reduced iNOS expression. In conclusion, AMPK-mediated PI3K/mTOR, Nrf2, and NF-κB signaling pathways may all be involved in the therapeutic benefits of TRI for CIPN. These results indicate that TRI may be useful for reducing the side effects of CIPN and enhancing patient outcomes during cisplatin chemotherapy.
顺铂诱导的周围神经病变（CIPN）是癌症治疗中使用的顺铂化疗的一种常见副作用，会使人衰弱。本研究探讨了曲美他嗪 (TRI) 通过保护神经完整性、减少神经氧化应激和减轻神经炎症对 CIPN 的神经保护作用。我们利用大鼠 CIPN 模型，评估了 TRI 对运动协调性、疼痛敏感性和周围神经组织病理学的影响。此外，我们还评估了 TRI 对神经氧化应激和神经炎症标志物的影响。研究结果表明，患有 CIPN 的大鼠运动协调性更差，对疼痛的敏感性更高，但 TRI 治疗可减轻这些症状，且效果与剂量相关。接受 TRI 治疗后，神经传导速度恢复正常，参与神经病变信号转导的基因表达受到抑制。TRI 还具有抗氧化功效，可减少氧化损伤，恢复细胞能量平衡。通过抑制炎症标志物的产生，TRI 还具有抗炎特性。组织病理学检查显示，TRI（尤其是在给药剂量较大时）可抑制神经纤维的变性和脱髓鞘。TRI 在坐骨神经中的抗炎特性还体现在它能减少 iNOS 的表达。总之，AMPK 介导的 PI3K/mTOR、Nrf2 和 NF-κB 信号通路可能都参与了 TRI 对 CIPN 的治疗作用。这些结果表明，在顺铂化疗期间，TRI 可能有助于减轻 CIPN 的副作用并提高患者的预后。
{"title":"Neuroprotective Effects of Trimetazidine against Cisplatin-Induced Peripheral Neuropathy: Involvement of AMPK-Mediated PI3K/mTOR, Nrf2, and NF-<i>κ</i>B Signaling Axes.","authors":"Marawan A Elbaset, Sherif M Afifi, Tuba Esatbeyoglu, Sahar S Abdelrahman, Dalia O Saleh","doi":"10.1155/2024/6612009","DOIUrl":"10.1155/2024/6612009","url":null,"abstract":"<p><p>Cisplatin-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cisplatin chemotherapy used in cancer treatment. This study explored the neuroprotective effects of Trimetazidine (TRI) against CIPN by preserving nerve integrity, reducing neuro-oxidative stress, and alleviating neuroinflammation. Using a rat model of CIPN, we evaluated TRI's impact on motor coordination, pain sensitivity, and peripheral nerve histopathology. Also, its effects on neuro-oxidative stress and neuroinflammatory markers were assessed. The findings showed that rats with CIPN had worse motor coordination and increased sensitivity to pain but that these symptoms were alleviated by TRI therapy in a dose-dependent way. Nerve conduction velocities were normalized, and expression of genes involved in neuropathy signaling was suppressed after TRI therapy. Antioxidant benefits were also shown in TRI, with oxidative damage being reduced and the cellular energy balance being restored. By inhibiting the production of inflammatory markers, it also demonstrated anti-inflammatory properties. Histopathological examination revealed that TRI, especially when administered at a higher dose, inhibited the degeneration and demyelination of nerve fibers. The anti-inflammatory properties of TRI in the sciatic nerves were further shown by the fact that its administration reduced iNOS expression. In conclusion, AMPK-mediated PI3K/mTOR, Nrf2, and NF-<i>κ</i>B signaling pathways may all be involved in the therapeutic benefits of TRI for CIPN. These results indicate that TRI may be useful for reducing the side effects of CIPN and enhancing patient outcomes during cisplatin chemotherapy.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"2024 ","pages":"6612009"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584005","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}
Pub Date : 2024-08-10eCollection Date: 2024-01-01DOI: 10.1155/2024/5594090
Naif AlSuhaymi
Background: 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.
Aim: To evaluate and compare the therapeutic effects of Nigella sativa (N. sativa) seed and oil on the biochemical parameters and regeneration of pancreatic islets (or islets of Langerhans) of streptozotocin (STZ)-induced diabetic rats.
Materials and methods: 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 N. sativa 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.
Results: Treatment of STZ-diabetic rats with N. sativa seeds or oil significantly improved their serum glucose levels, lipid profiles, and liver and renal functions as well as preserved the integrity of pancreatic β cells.
Conclusion: N. sativa 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 N. sativa seeds and oil on DM and its related complications are comparable.
{"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":"2024 ","pages":"5594090"},"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}
Pub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.1155/2024/5632260
Yanjun Mao, Qinglin Yang, Junhong Liu, Yuxin Fu, Shuaishuai Zhou, Jiayan Liu, Linlin Ying, Yao Li
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-γ) were significantly decreased in the 500 and 750 mg/kg quercetin treatments (P < 0.05); quercetin significantly decreased diarrhea rate and diarrhea index (P < 0.05) and significantly increased the content of serum transforming growth factor (TGF-β) in weaned piglets (P < 0.05); the content of serum NF-κB was significantly decreased in the 750 mg/kg quercetin treatment (P < 0.05); moreover, quercetin significantly increased diversity of colonic flora (P < 0.05), and at the phylum level, the relative abundance of Actinobacteria in the 500 and 750 mg/kg treatments was significantly increased (P < 0.05), and the relative abundance of Proteobacteria in the three quercetin treatments were significantly decreased (P < 0.05) in the colon of weaned piglets; at the genus level, the relative abundance of Clostridium-sensu-stricto-1, Turicibacter, unclassified_f_Lachnospiraceae, Phascolarctobacterium, and Family_XIII _AD3011_group was significantly increased (P < 0.05); the relative abundance of Subdollgranulum and Blautia was significantly decreased in the 500 and 750 mg/kg treatments (P < 0.05); the relative abundance of Eschericha-Shigella, Terrisporobacter, and Eubacterium-coprostanoligenes was significantly increased (P < 0.05); the relative abundance of Streptocococcus, Sarcina, Staphylococcus, and Ruminococcaceae_UCG-008 was significantly decreased in the three quercetin treatments (P < 0.05); the relative abundance of Ruminococcaceae_UCG_014 was significantly increased in the 250 mg/kg quercetin treatment in the colon of weaned piglets (P < 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-κB (NF-κB) signal pathway (P < 0.05); mRNA expression of tumor necrosis factor-α (TNF-
{"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":"2024 ","pages":"5632260"},"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}
Pub Date : 2024-08-01eCollection Date: 2024-01-01DOI: 10.1155/2024/2121733
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
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.
{"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":"2024 ","pages":"2121733"},"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}
Introduction: 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 Aloe vera on oxidative stress, blood-brain barrier (BBB) permeability, and neurological scores following TBI.
Materials and methods: Adult male rats were categorized into five groups: sham, TBI, vehicle, low-dose Aloe vera (LA), and high-dose Aloe vera (HA). We induced diffuse TBI using the Marmaro model and administered the aqueous Aloe vera 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.
Results: Both LA and HA reduced the increase in BBB permeability after TBI, with HA having a more pronounced effect than LA. Both Aloe vera doses decreased brain MDA levels, increased brain TAC, and lowered both serum and brain PC levels. The impact of Aloe vera 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.
Conclusion: This study suggests that Aloe vera extract may reduce BBB permeability and improve neurological outcomes after TBI by decreasing oxidative factors and increasing antioxidant factors.
{"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":"2024 ","pages":"5586814"},"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}
Pub Date : 2024-06-26eCollection Date: 2024-01-01DOI: 10.1155/2024/4887877
Vikram Subramanian, Denise Juhr, Lydia S Johnson, Justin B Yem, Piero Giansanti, Isabella M Grumbach
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.
{"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":"2024 ","pages":"4887877"},"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}
Pub Date : 2024-06-20eCollection Date: 2024-01-01DOI: 10.1155/2024/4293391
Fatemeh Abbaszadeh, Pegah Javadpour, Mohammad Mehdi Mousavi Nasab, Masoumeh Jorjani
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.
{"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":"2024 ","pages":"4293391"},"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}
Sonia Thapa, Yedukondalu Nalli, Ajeet Singh, Shashank Kr. Singh, Asif Ali
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 Cannabis sativa 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.
{"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":"52 1","pages":""},"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}
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 (n = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT perse. 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.
心肌梗死（MI）是由于长时间缺血/缺氧对心肌组织造成的不可逆损伤，随后导致收缩功能丧失和心肌损伤。然而，在危险期过后，缺血再灌注（IR）本身会导致氧自由基的产生、阳离子平衡的紊乱、细胞能量储存的耗竭以及先天性和适应性免疫反应的激活。本研究采用的阿巴他赛普（ABT）是一种抗炎药物，最初用作抗风湿反应剂。为了研究 ABT 的心脏保护潜力，首先在化学诱导的心肌坏死模型中优化了剂量。此后，在心肌红外损伤的手术模型中，将动物（n = 30）随机分为五组，以 5 mg/kg s.c. OD 的剂量对 ABT 的心脏保护潜力进行了研究：Sham 组、IR-C 组、Telmi10 + IR 组（替米沙坦，10 毫克/千克口服）、ABT5 + IR 组、ABT perse.ABT和替米沙坦给药21天。第21天，对动物进行LAD冠状动脉闭塞60分钟，然后再灌注45分钟。此外，还通过血液动力学参数、氧化-抗氧化生化酶学参数、心脏损伤、炎症标志物、组织病理学分析、TUNEL检测和免疫组织化学评估来评估心脏保护潜力，然后通过免疫印迹来探索信号通路。统计采用单因素方差分析，然后进行Tukey比较事后检验。值得注意的是，ABT 预处理 21 天可改善心肌梗死大鼠模型的血液动力学和心室功能。ABT的心脏保护潜力伴随着抑制MAP激酶信号转导和调节Nrf-2/HO-1蛋白下游信号级联。总之，本研究加强了之前已知的 ABT 在心肌梗死中的抗炎作用，并有助于从机理上深入了解和应用临床批准的药物来避免炎症反应的激活。
{"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":"39 1","pages":""},"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}
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.
{"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":"89 1","pages":""},"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}
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