Valverde M, Rosales-Cruz P, Torrejon-Gonzalez E
… +3 more, Ponce-Ortiz A, Rodriguez-Sastre MA, Rojas E
Oxid Med Cell Longev
· 2024 · PMID 39722890
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Occupational exposure to arsenic (As), cadmium (Cd), and lead (Pb) affects many sectors, necessitating research to understand their transformation mechanisms. In this study, we characterized the process of epithelial-mes...Occupational exposure to arsenic (As), cadmium (Cd), and lead (Pb) affects many sectors, necessitating research to understand their transformation mechanisms. In this study, we characterized the process of epithelial-mesenchymal transition (EMT) in a rat hepatic epithelial cell line with decreased expression of catalase and glutamate cysteine ligase catalytic (GCLC) subunit that was exposed to a mixture of As, Cd, and Pb at equimolar occupational exposure concentrations. We evaluated the expression of genes and proteins involved in EMT. Our findings revealed that cells with a decreased antioxidant barrier showed a decreased expression and abundance of epithelial genes when exposed to a mixture of metals. Additionally, we observed alterations in the expression of transcription factors (TFs) associated with EMT and an increase in the expression and abundance of mesenchymal genes. Specifically, we found that E-cadherin expression decreased by ~50% at both the gene and protein levels. In contrast, the expression of , , and genes increased by ~70%, whereas their corresponding protein levels increased by nearly 100%. Furthermore, the TFs zinc finger e-box binding homeobox 1 and snail family transcriptional repressor 1 showed a 30% increase in gene expression and an ~80% increase in protein expression. These changes enable the cells to acquire migratory capabilities. Our results confirmed that exposure to this mixture of As, Cd, and Pb can induce EMT in cells with a decreased antioxidant barrier.
Oxid Med Cell Longev
· 2024 · PMID 39720557
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Schistosomiasis is considered one of the most devastating parasitic diseases globally, coming second only to malaria in terms of morbidity. The disease-causing parasite can inhabit the body for over a decade, leading to...Schistosomiasis is considered one of the most devastating parasitic diseases globally, coming second only to malaria in terms of morbidity. The disease-causing parasite can inhabit the body for over a decade, leading to imbalances in the host's metabolic systems. The flukes and their eggs can illicit various immunological and metabolic complications resulting in the generation of reactive oxygen species (ROS). These are known to have several devastating effects on the host through increased oxidative stress, DNA mutation, and gene modifications, which can lead to fibrosis and cancer. Here, we discuss oxidative stress and cancer risk in Schistosoma infection. The concept of ROS generation and the complex antioxidant systems that enable the parasite to evade oxidant insults and prolong its life span in the host are explored. Further, the various roles of ROS during the initiation and progression of schistosomiasis and its influence on the host are discussed. Finally, mechanisms linked to the risk of bladder cancer in () infections are elucidated. Finally, we provide an opinion on how some of these mechanisms could give directions for future studies as well as provide a springboard for diagnostics and drug targeting in schistosomiasis.
Oxid Med Cell Longev
· 2024 · PMID 39640288
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Lipopolysaccharide (LPS)-induced activation of microglia triggers the release of neuroinflammatory molecules, contributing to the progression of neurodegenerative diseases. Targeting these neuroinflammatory molecules cou...Lipopolysaccharide (LPS)-induced activation of microglia triggers the release of neuroinflammatory molecules, contributing to the progression of neurodegenerative diseases. Targeting these neuroinflammatory molecules could serve as a potential therapeutic strategy. Given the evidence supporting the immune-boosting properties of curcumin (Curc) and the protective effects of monophosphoryl lipid A (MPL) in the central nervous system (CNS) related to Alzheimer's disease (AD), this study aimed to assess the anti-inflammatory effects of these compounds on primary rat microglial cells, which are crucial in the response to neuroinflammation. This in vitro study investigated the effects of Curc, MPL, and their coadministration (Curc + MPL) on inflammatory cytokine levels in activated microglial cells. Primary microglial cells were isolated from 1-day-old rats and treated with various concentrations of Curc, MPL, and Curc + MPL prior to LPS stimulation. Cell viability was assessed using the MTT assay, followed by the Griess assay to evaluate nitric oxide (NO) production. The levels of inflammatory cytokines interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-), and interleukin-6 (IL-6), as well as the gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), were analyzed via real-time PCR. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the protein levels of IL-1, TNF-, and IL-6. Our findings demonstrate that Curc and MPL possess antineuroinflammatory properties in LPS-stimulated microglial cells. Notably, the coadministration of Curc and MPL (Curc + MPL) significantly inhibited the production of pro-inflammatory cytokines IL-1, TNF-, and IL-6. Furthermore, Curc + MPL suppressed the expression of iNOS and COX-2. These results strongly suggest that Curc + MPL is a promising neuroprotective agent for the treatment of neurodegenerative disorders by mitigating neuroinflammatory responses.
Elbaset MA, Afifi SM, Esatbeyoglu T
… +2 more, Abdelrahman SS, Saleh DO
Oxid Med Cell Longev
· 2024 · PMID 39502494
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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 C...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-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.
Oxid Med Cell Longev
· 2024 · PMID 39483849
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, which is known as a drumstick tree in different areas of the world, is well-known for many health benefits, which are attributed to the abundance of flavonoids, phenolic chemicals, and thiocyanates it contains. This re..., which is known as a drumstick tree in different areas of the world, is well-known for many health benefits, which are attributed to the abundance of flavonoids, phenolic chemicals, and thiocyanates it contains. This review focuses on 's potential for neuroprotection, emphasizing its anti-inflammatory, antioxidant, and neurotransmitter-modulating qualities. Different parts of include leaves, roots, bark, and gum. Flowers, seeds, and seed oil are used for many health purposes, most notably in the treatment of neurological diseases. Neurodegeneration, which is characterized by the progressive death of nerve cells, is a major concern with an aging population, leading to disorders such as dementia and movement disorders. bioactive compounds improve the antioxidant defense activities of the brain, reduce inflammation, and improve neurotransmitter levels, showing potential therapeutic applications for neurodegenerative disorders. This review emphasizes the importance of further research, especially clinical trials, to fully understand and utilize 's neuroprotective capabilities.
Heisler EV, Osmarim Turra B, Cardoso de Afonso Bonotto N
… +11 more, da Cruz IBM, Aurélio Echart Montano M, Farina Azzolin V, Dal Magro J, Zaniol F, Perottoni J, Chelotti ME, Dos Santos Trombini F, Maia-Ribeiro EA, Barbisan F, Schimith MD
Oxid Med Cell Longev
· 2024 · PMID 39411276
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Diabetes mellitus is associated with chronic wound-healing problems that significantly impact patients' quality of life and substantially increase expenditure on healthcare. Therefore, the identification of compounds tha...Diabetes mellitus is associated with chronic wound-healing problems that significantly impact patients' quality of life and substantially increase expenditure on healthcare. Therefore, the identification of compounds that can aid healing is justified. (Ten.) has been used in folk medicine for curative purposes; however, the causal mechanisms underlying its healing effects remain to be elucidated. In this study, the effect of the ethanolic extract of was evaluated in an healing model using fibroblasts cultivated under normoglycemic and hyperglycemic environments. The extract was predominantly composed of phytol and exhibited genoprotective activity. Fibroblast migration attenuated the adverse effects of hyperglycemia, favoring cell proliferation. Collagen levels were significantly increased in ruptured fibroblasts under both standard and hyperglycemic environments. The phytogenomic effect of the extract on three genes related to extracellular matrix formation, maintenance, and degradation showed that increased the expression of genes related to matrix synthesis and maintenance in both normoglycemic and hyperglycemic individuals. Furthermore, it reduced the expression of genes related to matrix degradation. Overall, this is the first study to demonstrate the effectiveness of in wound healing, elucidating possible causal mechanisms that appear to be based on the genoprotective effect of this plant on the migratory and proliferative phases of the wound healing process; these effects are probably related to phytol, its main constituent.
Mulè S, Ferrari S, Rosso G
… +5 more, Galla R, Battaglia S, Curti V, Molinari C, Uberti F
Oxid Med Cell Longev
· 2024 · PMID 39380915
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During ageing, the brain is vulnerable to a growing imbalance of the antioxidant defence system, resulting in increased oxidative stress. This condition may be mainly responsible for cognitive decline, resulting in synap...During ageing, the brain is vulnerable to a growing imbalance of the antioxidant defence system, resulting in increased oxidative stress. This condition may be mainly responsible for cognitive decline, resulting in synaptic transmission disruptions and the onset of neuronal dysfunction. In this context, developing efficient preventive and therapeutic strategies against increased oxidative stress and decreased antioxidant defence mechanisms should be considered a public health priority to promote healthy ageing. Therefore, the current study explored the benefits of a novel combination of green tea, saffron, trans-Reveratrol, and citicoline, called MIX, on improving intracellular processes to ameliorate the mechanisms linked to cognitive decline under oxidative stress conditions. First, the ability of MIX to cross the blood-brain barrier (BBB) was evaluated in an model, analysing TEER value and the specific tight junctions; second, the CCF-STTG1 cell line was pretreated with 200 M HO for 30 min to explore the effects of the single active compounds and their combination under oxidative stress conditions. Our results demonstrated for the first time the synergistic effects of the new combination to improve the absorption rate of individual agents through the BBB and maintain its integrity. Subsequently, further research was done to assess the positive role of the combination to counteract oxidative damage; as expected, MIX restored the neurodegenerative state activated by 200 M HO, reducing mitochondrial damage, and improving survival pathways. Additionally, MIX acted as a regulator of both cellular energy metabolism and apoptosis, reducing the inflammatory state activated by oxidative stress. Finally, MIX can balance neurotrophin production to prevent mitochondrial disruption. In conclusion, MIX counteracted the adverse effects of brain oxidative stress, suggesting that this new proposed formulation prevents the molecular mechanisms underlying the onset of cognitive decline, even in support of conventional therapy.
Primo MGS, da Silva LAA, de Carvalho VBL
… +13 more, de Azevedo MAF, Monteiro NVDN, Mendes VR, da Silva JKM, Oliveira ASDSS, Brito AKDS, Sales ALCC, Mallet JRDS, Parente JML, de Matos Neto EM, Ferreira PMP, Arcanjo DDR, Martins MDCCE
Oxid Med Cell Longev
· 2023 · PMID 39263681
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OBJECTIVE: This research aimed to assess the intake of vitamin E and its relationship with lipid peroxidation markers and C-reactive protein levels in patients with flu symptoms and COVID-19 diagnosis. METHODS: A cross-s...OBJECTIVE: This research aimed to assess the intake of vitamin E and its relationship with lipid peroxidation markers and C-reactive protein levels in patients with flu symptoms and COVID-19 diagnosis. METHODS: A cross-sectional study with 121 patients of both sexes assisted at two basic health units in the city of Teresina, Piauí, with COVID-19 diagnosis confirmed through real-time reverse transcription polymerase chain reaction, was performed between the 3 and 7 days of flu symptoms. The global nutritional status and the measurement of waist circumference were assessed according to the World Health Organization recommendations. The dietary energy intake, macronutrients, and vitamin E consumption were assessed through the 24 hr food recall method. The malondialdehyde plasmatic concentration (MDA) was measured through the method of thiobarbituric acid-reactive substances. Myeloperoxidase (MPO) was assessed through the oxidation speed of the o-dianisidine substrate in the presence of hydrogen peroxide. C-reactive protein (CRP) levels were measured by a high-sensitivity immunoturbidimetry method. RESULTS: The most common symptoms reported by the participants were sore throat, fever, and cough. Regarding the global nutritional status evaluation, the majority of the sample had overweight. The dietary intake of vitamin E was 100% inadequate and presented a mild correlation ( = 0.197) with MDA, a redox status marker. No correlation was observed among MPO, CRP, and the dietary intake of vitamin E. CONCLUSION: The dietary intake of vitamin E was related to MDA as the marker of redox status.
Oxid Med Cell Longev
· 2024 · PMID 39247668
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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...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%, < 0.001), ventricular tachycardia (34.150 ± 1.59%, < 0.001), and ventricular fibrillation (24.31 ± 1.02%, < 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.
Oxid Med Cell Longev
· 2024 · PMID 39156220
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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 effect...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 () 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 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 seeds or oil significantly improved their serum glucose levels, lipid profiles, and liver and renal functions as well as preserved the integrity of pancreatic cells. CONCLUSION: 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 seeds and oil on DM and its related complications are comparable.
Mao Y, Yang Q, Liu J
… +5 more, Fu Y, Zhou S, Liu J, Ying L, Li Y
Oxid Med Cell Longev
· 2024 · PMID 39139212
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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...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-) were significantly decreased in the 500 and 750 mg/kg quercetin treatments ( < 0.05); quercetin significantly decreased diarrhea rate and diarrhea index ( < 0.05) and significantly increased the content of serum transforming growth factor (TGF-) in weaned piglets ( < 0.05); the content of serum NF-B was significantly decreased in the 750 mg/kg quercetin treatment ( < 0.05); moreover, quercetin significantly increased diversity of colonic flora ( < 0.05), and at the phylum level, the relative abundance of Actinobacteria in the 500 and 750 mg/kg treatments was significantly increased ( < 0.05), and the relative abundance of Proteobacteria in the three quercetin treatments were significantly decreased ( < 0.05) in the colon of weaned piglets; at the genus level, the relative abundance of , , , , and was significantly increased ( < 0.05); the relative abundance of and was significantly decreased in the 500 and 750 mg/kg treatments ( < 0.05); the relative abundance of , , and was significantly increased ( < 0.05); the relative abundance of , , , and was significantly decreased in the three quercetin treatments ( < 0.05); the relative abundance of was significantly increased in the 250 mg/kg quercetin treatment in the colon of weaned piglets ( < 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-B (NF-B) signal pathway ( < 0.05); mRNA expression of tumor necrosis factor- (TNF-), interleukin-1R1 (IL-1R1), conserved helix-loop-helix ubiquitous kinase (CHUK), toll-like receptor 4 (TLR4), and IL-1 from quercetin treatments were significantly decreased in colonic mucosa of weaned piglets ( < 0.05). In summary, quercetin increased feed conversion ratio and decreased diarrhea through regulating NF-B signaling pathway, controlling the balance between anti-inflammatory and proinflammatory factors, and modulating intestinal flora, thus promoting the absorption of nutrients in weaned piglets. These results provided the theoretical foundation for applying quercetin in preventing weaning piglets' diarrhea and animal husbandry practices.
Urasheva ZU, Kabdrakhmanova GB, Yermagambetova AP
… +7 more, Utegenova AB, Seitmaganbetova NA, Aliyev OM, Kurmangaliyeva SS, Kenzhina NK, Kurmambayev YZ, Khamidulla AA
Oxid Med Cell Longev
· 2024 · PMID 39119484
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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 bibliometri...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.
Khaksari M, Shahryari M, Raji-Amirhasani A
… +4 more, Soltani Z, Bibak B, Keshavarzi Z, Shakeri F
Oxid Med Cell Longev
· 2024 · PMID 39040520
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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...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 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 (LA), and high-dose (HA). We induced diffuse TBI using the Marmaro model and administered the aqueous 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 doses decreased brain MDA levels, increased brain TAC, and lowered both serum and brain PC levels. The impact of 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 extract may reduce BBB permeability and improve neurological outcomes after TBI by decreasing oxidative factors and increasing antioxidant factors.
Subramanian V, Juhr D, Johnson LS
… +3 more, Yem JB, Giansanti P, Grumbach IM
Oxid Med Cell Longev
· 2024 · PMID 38962180
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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 intracerebr...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.
Verma VK, Mutneja E, Malik S
… +7 more, Sahu AK, Prajapati V, Bhardwaj P, Ray R, Nag TC, Bhatia J, Arya DS
Oxid Med Cell Longev
· 2024 · PMID 38957586
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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 perio...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 ( = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT . 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.
Abbaszadeh F, Javadpour P, Mousavi Nasab MM
… +1 more, Jorjani M
Oxid Med Cell Longev
· 2024 · PMID 38938696
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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 effecti...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.
Thapa S, Nalli Y, Singh A
… +2 more, Singh SK, Ali A
Oxid Med Cell Longev
· 2024 · PMID 38855429
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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...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 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.
Takasaki T, Hamabe Y, Touchi K
… +7 more, Khandakar GI, Ueda T, Okada H, Sakai K, Nishio K, Tanabe G, Sugiura R
Oxid Med Cell Longev
· 2024 · PMID 38500550
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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...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.
Amini R, Moradi S, Najafi R
… +2 more, Mazdeh M, Taherkhani A
Oxid Med Cell Longev
· 2024 · PMID 38425997
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BACKGROUND: Neurological disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves...BACKGROUND: Neurological disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). OBJECTIVES: In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. METHODS: This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood-brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. RESULTS: Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. CONCLUSION: The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.