Iranian Journal of Basic Medical Sciences最新文献

{"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}

{"title":"Lysyl oxidase-like 2 promotes the survival, migration, and ferroptosis of endometrial cancer cells by activating the phosphoinositide 3-kinase/protein kinase B pathway.","authors":"Jiashi Gu, Huanmei Sun, Juan Shao, Hu Zhang, Zhanpeng Zhu, Dongqin Ma, Yingchun Duan","doi":"10.22038/ijbms.2024.79933.17317","DOIUrl":"10.22038/ijbms.2024.79933.17317","url":null,"abstract":"<p><strong>Objectives: </strong>LOXL2, known as Lysyl oxidase-like 2, is classified as a lysyl oxidase (LOX) family member. However, its role and mechanism in endometrial cancer (EC) are unknown. Therefore, we aimed to investigate the potential role and mechanism of LOXL2 in EC.</p><p><strong>Materials and methods: </strong>The levels of LOXL2 expression in EC tissues and normal adjacent tissues were evaluated by immunohistochemically (IHC) labeling. Following the dye application, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell methodologies were executed to evaluate the effects of LOXL2 inhibition and up-regulation on the growth, programmed cell death, migration, and susceptibility to iron-dependent cell death of EC. Moreover, protein analysis through Western blotting and gene expression analysis using Real-time quantitative PCR (RT-qPCR) was employed to measure the levels of pertinent biomarkers.</p><p><strong>Results: </strong>LOXL2 is highly expressed in both EC tissues and serum in vivo. Silencing LOXL2 reduced EC cell proliferation and migration while increasing apoptosis <i>in vitro</i>. LOXL2 silencing increased the ferroptosis-related proteins Solute Carrier Family 7 Member 11 (SLC7A11) and Ferritin Heavy Chain 1 (FTH1) while decreasing Glutathione Peroxidase 4 (GPX4) (both, <i>P<</i>0.001). Additionally, LOXL2 silencing reduced the p-PI3K and p-Akt protein expression, while LOXL2 overexpression (OE-LOXL2) elevated the p-PI3K and p-Akt protein expression (both, <i>P<</i>0.001). Additionally, LOXL2 silencing increases SLC7A11 and FTH1 while decreasing GPX4 (both <i>P<</i>0.001). LOXL2 overexpression has the opposite effect. However, the LY294002 inhibitor restores SLC7A11 and FTH1 expression while decreasing GPX4 (<i>P<</i>0.001).</p><p><strong>Conclusion: </strong>Our research demonstrated that LOXL2 might protect EC via phosphorylation by activating the PI3K/AKT pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"72-79"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059073","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":"Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis.","authors":"Daoyuan Lv, Laping Chu, Yuan Du, Chunqing Li, Neng Bao, Yuqing Su, Gang Wang, Yanlie Zheng, Yafen Yu","doi":"10.22038/ijbms.2024.78960.17083","DOIUrl":"10.22038/ijbms.2024.78960.17083","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the natural product sulforaphane (SFN) in protection of membranous nephropathy (MN) by inhibiting oxidative stress-associated podocyte pyroptosis.</p><p><strong>Materials and methods: </strong>A passive Heymann nephritis (PHN) model was established and treated with SFN. Clinical manifestations were examined by testing 24-hr urine protein, albumin, total cholesterol, triglyceride, high-density and low-density lipoprotein levels. Podocyte injury was observed through glomerular ultrastructure and the expression of podocin and desmin. Intrarenal oxidative stress was evaluated through assessment of oxidative markers, including malondialdehyde, 8-isoprostane, and 8-hydroxydeoxyguanosine, and the activities of anti-oxidant enzymes, including total superoxide dismutase, catalase, and γ-glutamylcysteine synthetase. Podocyte and intrarenal pyroptosis were investigated by observing the localization of the GSDMD N-terminus (GSDMD(N)) in podocytes; the expression of pyroptosis signaling pathway, including GSDMD, NF-κB p65, p-NF-κB p65 (Ser536), NLRP3, ASC, caspase-1, IL-1β, and IL-18; and pyroptosis encounter Nrf2 in the glomeruli and kidney.</p><p><strong>Results: </strong>SFN has a protective effect on MN, as reflected by alleviation of nephrotic syndrome, amelioration of podocyte foot process fusion, increased expression and normalization of podocin, and decreased expression of desmin in the glomeruli. Mechanistically, SFN relieved intrarenal oxidative stress, as indicated by decreased renal malondialdehyde, 8-isoprostane, and 8-hydroxydeoxyguanosine and increased activity of total superoxide dismutase, catalase, and γ-glutamylcysteine synthetase. SFN also inhibited podocyte and intrarenal pyroptosis, as revealed by decreased colocalization of GSDMD (N) with synaptopodin and ZO-1, decreased expression of pyroptosis signaling pathway, and increased expression of Nrf2 in the glomeruli and kidney.</p><p><strong>Conclusion: </strong>SFN could alleviate MN by inhibiting oxidative stress-associated podocyte pyroptosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"237-244"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028713","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":"Evaluating ginkgetin from <i>Ginkgo biloba</i> as a novel agent for sleep promotion through molecular docking and <i>in vivo</i> studies.","authors":"Mir Behrad Aghazadeh Ghadim, Ebrahim Salimi-Sabour, Alireza Shahriari, Mahdi Niazi, Farideh Bahrami","doi":"10.22038/ijbms.2025.82718.17878","DOIUrl":"https://doi.org/10.22038/ijbms.2025.82718.17878","url":null,"abstract":"<p><strong>Objectives: </strong>Sleep impacts the well-being and quality of life of millions. Given conventional pharmacotherapy's limitations and side effects, the quest for adequate and proper sleep promotion is imperative. This study aims to identify a suitable and effective compound for sleep by examining qualified herbal compounds in the PubChem database using <i>in silico</i> methods. Ultimately, the extracted compound (ginkgetin, a bioactive flavonoid from <i>Ginkgo biloba</i>) through molecular docking by considering the GABAA receptors will be evaluated through the <i>in vivo</i> method in an animal model to serve as proof for the findings from the molecular docking process.</p><p><strong>Materials and methods: </strong>Utilizing a comprehensive approach, this research employed molecular docking to screen 2299 phytochemicals for their affinity towards the GABAA receptor, focusing on the GABA, benzodiazepine, and steroid-binding sites. Ginkgetin emerged as a top candidate due to its high binding affinity. Subsequent <i>in vivo</i> electrophysiological assessments in rats treated with <i>G. biloba</i> extract containing ginkgetin evaluated alterations in sleep architecture, REM, and NREM sleep phases.</p><p><strong>Results: </strong>Molecular docking identified ginkgetin as possessing the highest binding affinity among the screened phytochemicals. <i>In vivo</i> studies corroborated these findings, demonstrating that rats treated with <i>Ginkgo biloba</i> extract significantly enhanced REM and NREM sleep compared to controls.</p><p><strong>Conclusion: </strong>Ginkgetin, derived from <i>G. biloba</i>, shows promising potential as a novel therapeutic agent for sleep disorders, supported by its strong affinity to key receptor sites and its efficacy in modulating sleep architecture <i>in vivo</i>. These findings contribute to the expanding evidence base for the therapeutic use of <i>G. biloba</i> in sleep promotion and underscore the need for further research to elucidate the mechanisms and clinical applicability of ginkgetin in sleep disorder treatment.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 6","pages":"746-754"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023825","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}