Iranian Journal of Basic Medical Sciences最新文献

{"title":"Effect of ellagic acid on BDNF/PI3K/AKT-mediated signaling pathways in mouse models of depression.","authors":"Hatice Aslı Bedel, Coşkun Usta","doi":"10.22038/ijbms.2025.81230.17580","DOIUrl":"10.22038/ijbms.2025.81230.17580","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study is to investigate the possible role of the hippocampal BDNF-PI3K-AKT signaling pathway in the antidepressant-like activity of ellagic acid (EA) in mice.</p><p><strong>Materials and methods: </strong>Male BALB/C mice were divided into 5 groups; vehicle (0.1 ml/day), sertraline (5mg/kg), EA (1 mg/kg), EA+BKM120 (PI3K inhibitor), EA+MK2206 (AKT inhibitor). EA, sertraline and vehicle were injected intraperitoneally for 14 days. Locomotor activity was determined by open field test. The tail suspension test was used to detect the antidepressant-like effect. After behavioral tests, hippocampal tissue was obtained and Western blot analyzes were performed for BDNF and pAKT1.</p><p><strong>Results: </strong>Sertraline and EA provided a reduction in immobility time in the tail suspension test when compared with the control group. BKM120 and MK2206 administration reversed this effect of EA. No statistical difference was found between groups in terms of locomotor activity. EA treatment caused an increase in hippocampal BDNF and pAKT1 levels in mice. While inhibitory agent administrations did not affect the increase of BDNF induced by EA, MK2206 administration reversed the increase in pAKT1 observed with EA.</p><p><strong>Conclusion: </strong>It has shown that EA has an antidepressant-like effect in mice without changing locomotor activity, and this effect may be mediated by the BDNF-PI3K-AKT signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"493-497"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiotoxicity caused by acrylamide in rats can be alleviated as a result of suppression of oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis by morin treatment.","authors":"Fatma Cakmak, Sefa Kucukler, Cihan Gur, Mustafa Ileriturk, Murat Gul, Behcet Varisli","doi":"10.22038/ijbms.2024.81490.17634","DOIUrl":"10.22038/ijbms.2024.81490.17634","url":null,"abstract":"<p><strong>Objectives: </strong>The present study investigated whether morin has a protective effect against ACR-induced cardiac toxicity.</p><p><strong>Materials and methods: </strong>In this study, oxidative stress, inflammation, endoplasmic reticulum stress (ERS), and apoptosis markers in heart tissues were analyzed by different methods after ACR (38.27 mg/kg) and morin (50 or 100 mg/kg) oral administration for ten days to Sprague Dawley rats.</p><p><strong>Results: </strong>The data obtained showed that ACR induced lipid peroxidation by decreasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) enzyme activities, glutathione (GSH) levels and nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC) gene expressions. On the other hand, these markers approached the control group levels after morin treatment. Moreover, morin suppressed ACR-induced inflammatory genes. Morin down-regulated the related genes by reducing the ERS, exacerbated after ACR administration. In addition, it was observed that B-cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, and apoptotic peptidase activating factor 1 (apaf-1) expressions, elevated by ACR in the heart tissue, were suppressed after morin administration. Moreover, Bcl-2 expression was triggered by morin treatment. Thus, morin suppressed ACR-induced apoptosis.</p><p><strong>Conclusion: </strong>Taken together, morin may protect against ACR-induced cardiac injury by suppressing oxidative stress, inflammation, ERS, and apoptosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 3","pages":"376-384"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-pinene ameliorates liver fibrosis by suppressing oxidative stress, inflammation, and the TGF-β/Smad3 signaling pathway.","authors":"Fatemeh Noroozi, Masoumeh Asle-Rousta, Rahim Amini, Zeinab Sahraeian","doi":"10.22038/ijbms.2025.81693.17678","DOIUrl":"10.22038/ijbms.2025.81693.17678","url":null,"abstract":"<p><strong>Objectives: </strong>A monoterpene alpha-pinene possesses anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Here, we investigated the effect of alpha-pinene on molecular, biochemical, and histological changes induced by carbon tetrachloride (CCl₄) in the liver of male Wistar rats.</p><p><strong>Materials and methods: </strong>Animals were divided into four groups: Control, Pinene, CCl₄, and CCl₄.Pinene. Pinene and CCl₄.Pinene groups were given alpha-pinene (50 mg/kg/day) through intraperitoneal (IP) injections for six consecutive weeks. CCl₄ and CCl₄.Pinene groups received IP injections of CCl₄ (2 ml/kg twice weekly for six consecutive weeks).</p><p><strong>Results: </strong>The results revealed that alpha-pinene inhibited enhancing liver enzyme AST (<i>P</i><0.001), ALT (<i>P</i><0.001), ALP (<i>P</i><0.01), and GGT (<i>P</i><0.001) activity in CCl₄.Pinene rats. It reduced malondialdehyde (<i>P</i><0.05) and nitric oxide (<i>P</i><0.05) levels and increased the catalase enzyme activity (<i>P</i><0.05) and glutathione levels (<i>P</i><0.01) in the liver. Likewise, alpha-pinene suppressed proinflammatory and profibrotic gene expression and prevented significant histological damage and collagen deposition in the liver of these animals. Also, alpha-pinene reduced the expression of TLR4 (<i>P</i><0.01), NF-κB (<i>P</i><0.05), PI3K (<i>P</i><0.05), Akt (<i>P</i><0.05), mTOR (<i>P</i><0.01), TGF-β1 (<i>P</i><0.01), and Smad3 (<i>P</i><0.01) in the liver of rats receiving CCl₄.</p><p><strong>Conclusion: </strong>We concluded that alpha-pinene reduced CCl₄-induced liver fibrosis by lowering oxidative stress, suppressing liver inflammation, and inhibiting TLR4/NF-κB, TGF-β/Smad3, and PI3K/Akt/mTOR signaling pathways. Consequently, alpha-pinene may have potential therapeutic value in treating liver diseases.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"451-460"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative effect of morin on diclofenac-induced testicular toxicity in rats: An investigation into different signal pathways.","authors":"Hasan Şimşek, Nurhan Akaras, Cihan Gür, Sefa Küçükler, Mustafa İleritürk, Fatih Mehmet Kandemir","doi":"10.22038/ijbms.2025.79735.17270","DOIUrl":"10.22038/ijbms.2025.79735.17270","url":null,"abstract":"<p><strong>Objectives: </strong>Diclofenac (Diclo) is a therapeutic agent used in the treatment of pain and inflammatory diseases, but it is also toxic to the human body. Morin is a flavonoid found naturally in plants and has many biological and pharmacological activities, including anti-inflammatory, anti-oxidant, and anticancer activities. This study aimed to investigate the efficacy of Morin in Diclo-induced testicular toxicity.</p><p><strong>Materials and methods: </strong>Morin (50 mg/kg and 100 mg/kg) was administered orally for five days, while Diclo was administered intraperitoneally at 50 mg/kg on days 4 and 5. Biochemical, molecular, and histological methods were used to investigate oxidative stress, inflammation, apoptosis, and endoplasmic reticulum (ER) stress damage indicators in testicular tissue.</p><p><strong>Results: </strong>Morin treatment attenuated Diclo-induced oxidative stress damage by increasing anti-oxidant levels (SOD, CAT, GPx, GSH, Nrf-2, HO-1, and NQO1) and decreasing MDA levels, an indicator of lipid peroxidation. Morin reduced levels of the inflammatory mediators NF-κB protein. Increases in apoptotic Bax and Caspase-3 by Diclo were reduced by Morin, while decreased antiapoptotic Bcl-2 level was increased. Morin reduced Diclo-induced ER stress injury by decreasing ATF-6, PERK, IRE1, GRP-78, and CHOP levels. Also, Diclo decreased COX-2 levels.</p><p><strong>Conclusion: </strong>Overall, Morin may be an effective treatment of choice for testicular tissue damage associated with Diclo toxicity and may reduce the level of damage.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"507-515"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics analysis identifies dysregulation of miR-548F-3p and its hub gene in triple-negative breast cancer.","authors":"Samira Behroozi, Mahdieh Salimi, Najaf Allahyari Fard","doi":"10.22038/ijbms.2025.79808.17287","DOIUrl":"10.22038/ijbms.2025.79808.17287","url":null,"abstract":"<p><strong>Objectives: </strong>Triple-negative breast cancer (TNBC), which affects 15-20% of cases, lacks targeted therapies and poses challenges in treatment. MicroRNAs (miRNAs) are potential biomarkers and therapeutic targets in breast cancer. To unravel its unique regulatory role, this study focused on miRNA microarray analysis, particularly miR-548F-3p, in TNBC samples.</p><p><strong>Materials and methods: </strong>Using the GSE76275 dataset, gene expression profiles were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEGs) were identified using robust preprocessing. Weighted gene co-expression network analysis (WGCNA) explored gene modules and identified hub genes co-expressed with miR-548F-3p. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted. Survival analysis was used to assess the prognostic impact of the identified genes.</p><p><strong>Results: </strong>The study found 224 up-regulated DEGs, with miR-548F-3p exhibiting significant down-regulation. MultimiR identified 400 genes that were targeted by miR-548F-3p. WGCNA revealed a blue co-expression module, with 356 genes targeted by miR-548F-3p. A Venn diagram identified common genes, including VANGL2, BRCC3, ANP32E, and ANLN. Functional enrichment highlighted crucial pathways in TNBC pathogenesis, including mitotic spindle organization, spindle assembly checkpoint signaling, cell cycle, and amino acid (serine) metabolism. PPI network analysis identified hub genes, including FOXM1, KIF23, and CDC20. VANGL2, BRCC3, ANP32E, and ANLN were significantly associated with patient outcomes in survival analysis.</p><p><strong>Conclusion: </strong>This analysis highlighted TNBC's molecular landscape, emphasizing miR-548F-3p's regulatory role. The identified genes, VANGL2, BRCC3, ANP32E, and ANLN, offer insights into TNBC pathogenesis and potential therapeutic targets, laying the foundation for understanding their clinical implications in the intricate landscape of TNBC.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"434-443"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT5 prevents mitochondrial dysfunction and cardiac hypertrophy induced by RIP140.","authors":"Liying Liang, Yi Huang, Qiujuan Wang, Ye Hong, Honghui Zhen, Yanfang Chen","doi":"10.22038/ijbms.2024.80343.17390","DOIUrl":"10.22038/ijbms.2024.80343.17390","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect and mechanism of sirtuin5 (SIRT5) on mitochondrial dysfunction and cardiac hypertrophy induced by receptor-interacting protein 140 (RIP140).</p><p><strong>Materials and methods: </strong>The neonatal rat cardiomyocytes (NRCMs) and SD rats were treated with Angiotensin II (Ang II) to induce <i>in vitro</i> and <i>in vivo</i> model of cardiac hypertrophy. RIP140 was overexpressed by adenovirus infection, and SIRT5 was overexpressed by plasmid transfection. RIP140 and SIRT5 were knocked down by siRNA interference. The expression of RIP140, SIRT5, and biomarkers of cardiac hypertrophy were measured by qRT-PCR and western blot. The transcription levels of mitochondrial DNA-encoded genes were detected by qRT-PCR. Cell surface area and mitochondrial membrane potential were respectively detected by rhodamine-phalloidin and tetramethylrhodamine ethyl ester (TMRE) fluorescence analysis. Cellular oxygen consumption and ATP production were investigated using assay kits. All data are from at least three independent experiments.</p><p><strong>Results: </strong>The expression of SIRT5 was down-regulated in NRCMs and hearts treated with Ang II. Overexpression of SIRT5 protected cardiomyocytes from AngII-induced hypertrophy, whereas knockdown of SIRT5 resulted in cardiac hypertrophy. Moreover, since SIRT5 was regulated by the transcriptional coactivator, we also found that SIRT5 could be negatively regulated by the transcriptional corepressor RIP140 in cardiomyocytes. Furthermore, SIRT5 significantly attenuated energy metabolic dysregulation and mitochondrial dysfunction and exerted its protective role on myocardial hypertrophy under the regulation of RIP140.</p><p><strong>Conclusion: </strong>SIRT5 exerts a protective role in mitochondrial dysfunction and cardiac hypertrophy induced by RIP140.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"477-485"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mTOR pathway is involved in the process of platelet-rich plasma improving intervertebral disc degeneration.","authors":"Jing Luan, Qi Wang, Wei Zheng, Yongjin He","doi":"10.22038/ijbms.2024.79218.17163","DOIUrl":"10.22038/ijbms.2024.79218.17163","url":null,"abstract":"<p><strong>Objectives: </strong>Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. We aimed to assess PRP's efficacy and explore possible mechanisms using the intervertebral disc degeneration (IDD) model.</p><p><strong>Materials and methods: </strong>A total of 48 male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, IDD+PBS, and IDD+PRP (n=16, respectively). IL-1β (10 ng/ml) was used to establish a humanized IDD model in human lumbar nucleus pulposus (NP) tissues from 36 patients with degenerative disc disease. These NP cells were randomly divided into three groups: sham, IDD+PBS, and IDD+PRP (n=12, respectively). RT-PCR and western blot were used to detect the expression of aggrecan, collagen II, IL-1β, IL-6, TNF-α, Bcl-2, cleaved-Caspase 3, Bax and Akt/mTOR/p70S6K signaling pathway. A related assay kit was used to detect MDA, SOD, and GSH.</p><p><strong>Results: </strong>PRP affected the expression of aggrecan, collagen II, IL-1β, IL-6, TNF-α, MDA, SOD, GSH, Bcl-2, cleaved-Caspase 3, and Bax in IDD rats. Compared with the IDD+PBS group, the expression of <i>p-mTOR, p-p70/S6K</i>, and <i>p-Akt</i> was much lower in the rat IDD+PRP group (<i>P<</i>0.05). Similarly, with PRP treatment in the humanized IDD model, the expression of <i>p-mTOR, p-p70/S6K</i>, and <i>p-Akt</i> was also inhibited.</p><p><strong>Conclusion: </strong>PRP may be a potential therapy for IDD via the mTOR signaling pathway in regulating and affecting extracellular matrix degradation, inflammatory factors, oxidative stress, and apoptosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 3","pages":"393-400"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adropin exerts neuroprotection in an experimental rat model of Parkinson's disease.","authors":"Ayse Ozkan, Hande Parlak, Osman Sinen, Mehmet Bulbul, Mutay Aydin Aslan, Aysel Agar","doi":"10.22038/ijbms.2025.82498.17830","DOIUrl":"https://doi.org/10.22038/ijbms.2025.82498.17830","url":null,"abstract":"<p><strong>Objectives: </strong>This study was planned to elucidate the mechanism of the protective effect of adropin in an experimental rat model of Parkinson's Disease (PD).</p><p><strong>Materials and methods: </strong>Three-month-old male Wistar rats were randomly divided into four groups: i) Control, ii) Sham, iii) PD, and iv) PD+Adropin. The performance tests were performed seven days after the 6-Hydroxydopamine hydrochloride (6-OHDA) injection into the striatum. The immunoreactivities for tyrosine hydroxylase (TH), G protein-coupled receptor 19 (GPR19), and vascular endothelial growth factor receptor 2 (VEGFR2) were detected by immunohistochemistry (IHC) in the substantia nigra (SN). Dopamine levels were measured by mass spectrometry. Glycogen synthase kinase 3β (GSK3β) and pGSK3β (Ser9) protein levels were evaluated by western blot analysis.</p><p><strong>Results: </strong>Our study demonstrated that motor performances were significantly improved by adropin treatment. Central adropin injection prevented the loss of nigral dopaminergic neurons and induced VEGFR2 expression but not GPR19 compared to the PD group. The ratio of p-GSK3β/GSK3β did not differ between groups. However, the level of dopamine in SN was increased with adropin injection in the PD+Adropin group.</p><p><strong>Conclusion: </strong>Our findings reveal that adropin administration has a protective effect on nigral dopaminergic neurons and acts through the VEGFR2 signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 6","pages":"790-798"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury.","authors":"Yunxia Li, Yuxin Bai, Shiyu Tang, Ye Sun, Zhe Wang, Biao Yang, Guangyan Liu","doi":"10.22038/ijbms.2024.80242.17374","DOIUrl":"10.22038/ijbms.2024.80242.17374","url":null,"abstract":"<p><strong>Objectives: </strong>Particulate matter 2.5 (PM2.5), particles with an aerodynamic diameter less than 2.5 µm, affect lung function and increase respiratory disease incidence and mortality rate. The molecular mechanism of lung injury and epithelial damage after PM2.5 exposure is not completely clear.</p><p><strong>Materials and methods: </strong>Mouth-nose exposure of mice was performed with PM2.5 or neutral saline. <i>In vitro</i> experiments were conducted to investigate the role of the S100A9/AMPK pathway in PM2.5-mediated lung injury.</p><p><strong>Results: </strong>PM2.5 exposure in mice caused lung epithelial damage, alveolar wall thickening, and alveolar wall structure destruction. The 16S rRNA sequencing results suggested that the microecology structure of lung tissue was altered after PM2.5 exposure. Proteomic sequencing was performed to explore the underlying mechanism, and 71 differentially expressed proteins were identified. KEGG database analysis of the up-regulated differential proteins revealed regulatory networks, including fat digestion and absorption, the AMPK signaling pathway, and the PPAR signaling pathway. Moreover, PM2.5 exposure in mice increased the level of S100A9 and ROS, leading to reduction of the ATP level. To achieve a sufficient energy supply by increasing fatty acid transfer and oxidation, activated AMPK up-regulates CD36 and CPT1, which leads to mitochondrial damage of PM2.5-exposed cells and injury or death of lung epithelial cells. siRNA-S100A9 and AMPK inhibitors significantly reduced the occurrence of cell damage.</p><p><strong>Conclusion: </strong>These results may help to clarify biomarkers and specific mechanisms of lung tissue injury induced by PM2.5 exposure.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"121-129"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of combo therapy with coenzyme Q10 and mitochondrial transplantation on myocardial ischemia/reperfusion-induced arrhythmias in aged rats.","authors":"Soleyman Bafadam, Behnaz Mokhtari, Alireza Alihemmati, Reza Badalzadeh","doi":"10.22038/ijbms.2024.80092.17348","DOIUrl":"10.22038/ijbms.2024.80092.17348","url":null,"abstract":"<p><strong>Objectives: </strong>Ischemia/reperfusion (IR)-induced ventricular arrhythmia, which mainly occurs after the opening of coronary artery occlusion, poses a clinical problem. This study aims to investigate the effectiveness of pretreatment with coenzyme Q₁₀ (CoQ₁₀) in combination with mitochondrial transplantation on IR-induced ventricular arrhythmias in aged rats.</p><p><strong>Materials and methods: </strong>Myocardial IR induction was performed by left anterior descending coronary artery occlusion for 30 min, followed by re-opening for 24 hr. CoQ₁₀ was administered intraperitoneally at a dosage of 10 mg/kg/day for two weeks before inducing IR. At the start of reperfusion, 500 µl of the respiration buffer containing 6×10⁶±5×10⁵ mitochondria/ml of respiration buffer harvested from the pectorals major muscle of young donor rats were injected intramyocardially. To investigate arrhythmias, the heart's electrical activity during ischemia and the first 30 min of reperfusion were recorded by electrocardiogram. After 24 hr of reperfusion, cardiac histopathological changes, creatine kinase-MB, nitric oxide metabolites (NOx), oxidative stress markers (malondialdehyde, total anti-oxidant, superoxide dismutase, and glutathione peroxidase), and the expression of genes regulating mitochondrial fission/fusion were measured.</p><p><strong>Results: </strong>Pretreatment with CoQ₁₀ in combination with mitochondrial transplantation reduced ventricular arrhythmias, cardiac histopathological changes, and creatine kinase-MB levels. Simultaneously, this combined therapeutic approach increased myocardial NOx levels, fostering an improved oxidative balance. It also triggered the down-regulation of mitochondrial fission genes, coupled with the up-regulation of mitochondrial fusion genes.</p><p><strong>Conclusion: </strong>The combination of CoQ₁₀ and mitochondrial transplantation demonstrated a notable anti-arrhythmic effect by elevating NOx levels, reducing oxidative stress, and improving mitochondrial fission/fusion in aged rats with myocardial IRI.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"38-48"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}