Iranian Journal of Basic Medical Sciences最新文献

{"title":"An <i>in vivo</i> evaluation of the antifibrotic potential of inulin against bile duct ligation-induced liver fibrosis.","authors":"Yasaman Habibian-Fard, Mahsa Ale-Ebrahim, Parvaneh Mohseni-Moghaddam, Shadi Sarahroodi, Pejman Mortazavi","doi":"10.22038/ijbms.2026.88153.19044","DOIUrl":"10.22038/ijbms.2026.88153.19044","url":null,"abstract":"<p><strong>Objectives: </strong>Hepatic fibrosis is a major cause of liver-related mortality worldwide. This study evaluated the hepatoprotective and antifibrotic effects of inulin, a natural polysaccharide, in a rat model of cholestasis induced by bile duct ligation (BDL).</p><p><strong>Materials and methods: </strong>Thirty male Wistar rats (230-250 g) were randomly divided into six groups: control, sham, inulin (200 mg/kg), BDL, and BDL+ inulin (100 and 200 mg/kg). Inulin was orally administered for 30 days after BDL. Serum liver enzyme levels, bilirubin, and lipid profiles were measured. Liver tissues were analyzed for oxidative stress markers (GPx, MDA), fibrogenic mediators (TGF-β1, α-SMA) via immunohistochemistry, and FXR levels by ELISA. Histological changes were evaluated by ELISA and Masson's trichrome staining.</p><p><strong>Results: </strong>At 200 mg/kg, inulin significantly reversed the BDL-induced increases in serum liver enzymes (AST, ALT, and ALP), total bilirubin, and cholesterol (<i>P</i><0.001 vs BDL group). Hepatic GPx and FXR levels were significantly increased (<i>P</i><0.001 vs BDL group), while MDA levels were decreased (<i>P</i><0.001 vs BDL group). Inulin markedly suppressed the expression of TGF-β1 and α-SMA (<i>P</i><0.01 vs BDL group). Histopathological evaluation showed notable improvement in liver architecture, with reduced fibrosis and necrosis (<i>P</i><0.001 vs BDL group).</p><p><strong>Conclusion: </strong>These findings suggest that inulin may exert antifibrotic effects through its anti-oxidant activity, ultimately reducing the expression of fibrogenic markers. This study presents strong histological evidence to support the hepatoprotective role of inulin.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 2","pages":"271-279"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722839","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":"Hepatoprotective effect of hUC-MSC secretome in LPS-induced HepG2 cells.","authors":"Wahyu Widowati, Philips Onggowidjaja, Massoud Vosough, Dwi Nur Triharsiwi, Anindita Putri Distya, Lisna Wahyu Nurani, Ismia Rahmawati, Any Aryani, Didik Priyandoko, Rizal Azis, Dhanar Septyawan Hadiprasetyo, Priyatharsini Rajendran, Kasim Sakran Abass, Safira Dinda Rifana","doi":"10.22038/ijbms.2026.93115.20079","DOIUrl":"https://doi.org/10.22038/ijbms.2026.93115.20079","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the cytotoxicity and hepatoprotective effects of human umbilical cord mesenchymal stem cell-derived secretome (hUCMSC-Sec) in lipopolysaccharide (LPS)-induced HepG2 cells as an in vitro model of liver inflammation.</p><p><strong>Materials and methods: </strong>hUCMSC-Sec was obtained from conditioned media of hUCMSCs at passage four. Inflammation was induced in HepG2 cells using LPS. Cytotoxicity was assessed using the WST-8 assay. Hepatoprotective effects of hUCMSC-Sec at concentrations of 12.5%, 4.17%, and 1.39% were evaluated by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and tumor necrosis factor-alpha (TNF-α). Gene expression levels of α-smooth muscle actin (α-SMA), SMAD-7, collagen type I alpha 1 (COL1A1), and matrix metalloproteinase-1 (MMP-1) were analyzed using quantitative real-time PCR.</p><p><strong>Results: </strong>hUCMSC-Sec concentrations ranging from 1.6% to 25% were non-toxic, maintaining cell viability above 90%. Treatment with hUCMSC-Sec significantly reduced ALT, AST, GGT, and TNF-α levels in LPS-induced HepG2 cells. In addition, hUCMSC-Sec down-regulated α-SMA, COL1A1, and MMP-1 expression, while up-regulating SMAD-7 expression. The concentration of 4.17% showed the most pronounced hepatoprotective effect.</p><p><strong>Conclusion: </strong>hUCMSC-derived secretome demonstrated hepatoprotective effects by attenuating inflammatory and fibrotic responses in LPS-induced HepG2 cells. However, as this study was limited to an in vitro model, further in vivo and clinical studies are required to confirm its therapeutic potential and translational applicability.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 6","pages":"901-908"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793153","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":"STAT3 ablation in keratinocytes ameliorates allergic contact dermatitis in DNCB-induced mice model.","authors":"Lu Chen, Cai Zhang, Liming Li, Huachun Wang, Wenchao Yao, Lei Xing, Jingyuan Gao, Zhengxiao Li, Faming Tian","doi":"10.22038/ijbms.2026.94064.20274","DOIUrl":"https://doi.org/10.22038/ijbms.2026.94064.20274","url":null,"abstract":"<p><strong>Objectives: </strong>Allergic contact dermatitis (ACD) is a T cell-mediated type IV hypersensitivity reaction to haptens. Its pathogenesis involves keratinocyte dysfunction and dysregulation of the Signal Transducer and Activator of Transcription 3 (STAT3)-signaling pathway. However, the specific role of keratinocyte produced STAT3 in ACD remains unclear. To investigate the effect of keratinocyte (KC)-specific STAT3 conditional knockout on 1-Chloro-2,4-dinitrobenzene (DNCB)-induced ACD in mice.</p><p><strong>Materials and methods: </strong>We generated keratinocyte-specific STAT3 conditional knockout (cKO) mice (K14-Cre⁺; STAT3^flox/flox) and subjected them to DNCB-induced ACD, with STAT3^flox/flox littermates as controls. Epidermal barrier function (transepidermal water loss and electrolyte permeability), histopathological inflammation (H&E and toluidine blue staining), and expression of inflammatory mediators (IL-1β, IL-6) were assessed. <i>In vitro</i>, STAT3 was knocked down by siRNA in HaCaT keratinocytes prior to stimulation with TNF-α/IFN-γ, followed by evaluation of inflammatory markers and STAT3 phosphorylation.</p><p><strong>Results: </strong>Keratinocyte-specific STAT3 deletion significantly ameliorated ACD severity, evidenced by reduced TEWL values, enhanced epidermal barrier function, decreased dermatitis scores, reduced clinical dermatitis scores, decreased dermal inflammatory infiltration, lower spleen index, and attenuated mast cell degranulation. Molecular analysis revealed down-regulation of inflammation-related factors (IL-1β, IL-6, TNF-α, JAK2) and significant inhibition of STAT3 phosphorylation. <i>In vitro</i>, STAT3 knockdown significantly suppressed IL-1β, IL-6, JAK2, Caspase-3, and MMP-3 expression in HaCaT cells and reduced STAT3 phosphorylation.</p><p><strong>Conclusion: </strong>Keratinocyte-specific STAT3 deletion alleviates epidermal barrier impairment and skin inflammation in ACD by inhibiting STAT3 phosphorylation and its downstream pro-inflammatory signaling.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 6","pages":"961-970"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793275","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":"Differential expression of the lncRNA MIR17HG and miR-18a/miR-20a as candidate ncRNA signatures in stage II/III breast cancer and bioinformatic analysis of ncRNA-mRNA regulatory axes.","authors":"Reyhane Alidousti Shahraki, Sara Tavallaei, Afsaneh Malekzadeh Shafaroudi, Saba Abbassioun, Nahid Nafissi, Seyed-Javad Mowla","doi":"10.22038/ijbms.2026.95193.20529","DOIUrl":"10.22038/ijbms.2026.95193.20529","url":null,"abstract":"<p><strong>Objectives: </strong>Breast cancer has remained a significant cause of mortality associated with cancer, necessitating a deeper molecular understanding to improve diagnostics and targeted therapies. Noncoding RNAs (ncRNAs) and their regulatory ncRNA-mRNA axes have recently emerged as important modulators of cancer progression and potential tools for earlier detection and more precise stratification of breast cancer. Among them, MIR17HG variants and the precise regulatory axes of miR-18a/miR-20a, and their mechanisms in stage II/III BC, remain elusive.</p><p><strong>Materials and methods: </strong>This study addresses this critical gap by integrating data from TCGA miRNAseq and RNAseq datasets with experimental qRT-PCR validation on patient tissues. We investigate MIR17HG transcript variants and their associated miRNAs, especially miR-18a and miR-20a, as candidate stage-associated molecules in stage II/III breast cancer. Co-expressed mRNAs were identified through gene co-expression networks (WGCNA).</p><p><strong>Results: </strong>Potential MIR17HG-miR-18a/20a-mRNA regulatory axes were computationally predicted and functionally annotated to elucidate their involvement in cancer-related signaling pathways. Our findings showed that both MIR17HG splice variants were down-regulated, while their associated miRNAs (miR-18a-5p and miR-20a-5p) were overexpressed. Based on <i>in silico</i> prediction and functional annotation, we propose three candidate MIR17HG-centred axes: MIR17HG-miR-20a-BTG3 (linked to RNA degradation), MIR17HG-miR-18a/miR-20a-PARD6B (Hippo signaling and cell polarity), and MIR17HG-miR-20a-ZNF367 (endocytosis-related processes).</p><p><strong>Conclusion: </strong>Together, these data support MIR17HG and its associated miRNAs as candidate stage II/III breast cancer-associated ncRNA signatures and provide a framework for future functional and clinical validation studies.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 11","pages":"1708-1718"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216064","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":"Britanin alleviates myocardial damage in rats with acute myocardial infarction by inhibiting the JAK2/STAT3 signaling pathway.","authors":"Yiqing Zhang, Xian Li, Hezi Jiang, Guoxing Zhang, Yafeng Zhou","doi":"10.22038/ijbms.2026.94760.20444","DOIUrl":"10.22038/ijbms.2026.94760.20444","url":null,"abstract":"<p><strong>Objectives: </strong>Acute myocardial infarction (AMI) is a life-threatening condition featuring coronary occlusion-induced myocardial ischemia-hypoxia, followed by tissue damage driven by calcium overload, inflammation, and pyroptosis. Current therapies offer limited myocardial protection. Britanin, a sesquiterpene lactone from Inula lineariifolia, has anti-inflammatory and antioxidant properties, while its role in AMI remains unclear. This study explored Britanin's therapeutic effects on rat AMI and underlying mechanisms, focusing on the JAK2/STAT3 signaling pathway.</p><p><strong>Materials and methods: </strong>Network pharmacology, molecular docking, and ProTox3.0 toxicity prediction were used for target screening and safety evaluation. Rat AMI models were established by left anterior descending ligation and treated with Britanin (5/10 mg/kg). Echocardiography, serum biochemistry, histopathological staining, Western blotting, and qPCR were used to assess cardiac function, myocardial injury, fibrosis, and molecular changes.</p><p><strong>Results: </strong>Pharmacology identified 30 overlapping targets, including JAK2, and highlighted JAK2/STAT3 as a key pathway. Britanin bound JAK2 strongly (binding energy <-8.2 kcal/mol); its LD₅₀ was 150 mg/kg, indicating safety. Britanin improved cardiac function indices, alleviated myocardial fibrosis, reduced serum injury markers, and down-regulated components of the JAK2/STAT3 pathway, the NLRP3 (NOD-like receptor pyrin domain-containing 3) inflammasome, and pyroptosis markers (all <i>P<</i>0.05), without liver or kidney toxicity.</p><p><strong>Conclusion: </strong>Britanin alleviates AMI-induced myocardial damage in rats by improving cardiac function, reducing injury and fibrosis, and inhibiting inflammation and pyroptosis through suppression of the JAK2/STAT3 pathway, positioning it as a potential AMI therapeutic agent.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 11","pages":"1719-1727"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216113","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":"Protective effects and mechanism of chrysophanol against age-related osteoporosis in rats.","authors":"Qing Lu, Chenxi Zhang, Lixia Ma, Xiaoyao Yu, Gan Zhang, Dagui Chen, Fusheng Shang","doi":"10.22038/ijbms.2026.87322.18864","DOIUrl":"10.22038/ijbms.2026.87322.18864","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the protective effect and underlying mechanism of chrysophanol (CPH) on senile osteoporosis (OP) in rats.</p><p><strong>Materials and methods: </strong>Twenty-four-month-old rats were divided into an aged OP model group and low- (10 mg/kg), medium- (20 mg/kg), and high-dose (50 mg/kg) CPH groups, with eight-month-old rats used as the control group. After 60 days of oral CPH administration, the bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (TbN), and trabecular separation (TbSp) of the femur were analysed using Micro-CT. Serum levels of bone formation markers (alkaline phosphatase, ALP; osteocalcin, OC) and bone resorption markers (type I collagen crosslinked N-telopeptide, NTX; tartrate-resistant acid phosphatase, TRACP) were determined by ELISA. Pathological changes in the femur were observed via H&E staining, and the expression of p-AKT and p-mTOR proteins in bone marrow was detected by western blotting.</p><p><strong>Results: </strong>Compared with those in the control group, the bone formation marker levels, BMD, BV/TV, and TbN in the model group significantly decreased, whereas the bone resorption marker levels, TbSp, and expression levels of p-AKT and p-mTOR significantly increased, with obvious bone structure destruction. CPH treatment reversed these changes in a dose dependent manner, significantly enhanced bone formation, inhibited bone resorption, improved bone density and microstructure, and down-regulated the expression of p-AKT and p-mTOR.</p><p><strong>Conclusion: </strong>CPH can effectively improve bone density and microstructure in aged osteoporotic rats, and its bone-protective effect may be related to the inhibition of the PI3K/AKT/mTOR signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 5","pages":"724-729"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251569","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":"Pitolisant disrupts memory consolidation and hippocampal synaptic plasticity: Impaired excitability and long-term potentiation in the CA1 area.","authors":"Siamak Beheshti, Adeleh Badiyifard, Zahra Badiei Darani, Mansour Azimzadeh, Alireza Halabian","doi":"10.22038/ijbms.2026.90953.19621","DOIUrl":"10.22038/ijbms.2026.90953.19621","url":null,"abstract":"<p><strong>Objectives: </strong>The histaminergic system plays a vital role in memory function, but the underlying cellular and circuit mechanisms remain poorly understood. Pitolisant, an inverse agonist of the histamine H3 receptor (H3R), is widely used in the treatment of narcolepsy and has shown potential anti-seizure effects. However, its impact on memory and synaptic plasticity is unclear. This study investigated the effects of intracerebroventricular administration of pitolisant on passive avoidance memory consolidation. Meanwhile, the impact of pitolisant on synaptic excitability, short-term plasticity, and long-term potentiation (LTP) in the hippocampus was investigated.</p><p><strong>Materials and methods: </strong>Adult male Wistar rats received pitolisant (10 or 100 µg/rat; ICV) or saline immediately after training in the passive avoidance apparatus to test memory consolidation. Meanwhile, pitolisant was microinjected into the CA₁ region to assess its targeted effects. Subsequently, field potentials were recorded to measure fundamental synaptic properties: input-output (I/O) function, paired-pulse facilitation, and LTP function.</p><p><strong>Results: </strong>Pitolisant significantly impaired memory consolidation. It also reduced the fEPSP slope in I/O function and paired-pulse facilitation, suggesting impaired synaptic excitability and increased presynaptic inhibition. Additionally, LTP was reduced in pitolisant-treated groups, indicating disrupted long-term plasticity.</p><p><strong>Conclusion: </strong>These findings highlight a potential inhibitory effect of pitolisant on passive-avoidance memory consolidation in healthy rats and on hippocampal synaptic function, raising concerns about its use in neurological disorders.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 3","pages":"378-386"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815309","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":"Therapeutic potential of a pullulan polysaccharide-based hydrogel with antibacterial peptide for skin wound healing.","authors":"Maziar Malekzadeh, Mehrdad Moosazadeh Moghaddam, Masoud Ghorbani","doi":"10.22038/ijbms.2026.90215.19450","DOIUrl":"10.22038/ijbms.2026.90215.19450","url":null,"abstract":"<p><strong>Objectives: </strong>Eliminating skin defects using scaffolds, especially hydrogels, has been a promising method to accelerate regeneration. The utilization of hydrogels composed of carboxymethyl chitosan and pullulan oxide, synthesized via Schiff base reaction, represents an effective approach for skin repair.</p><p><strong>Materials and methods: </strong>Carboxymethyl chitosan was reacted with oxidized pullulan (CMCS/OPL), and the hydrogel was formed. In addition, an antibacterial peptide was incorporated into a hydrogel. In <i>in vitro</i> conditions, the samples were evaluated by a characterization test. <i>In vivo</i>, H&E and real-time PCR tests were taken from the removed samples. Experiments confirmed the formation of the Schiff base reaction.</p><p><strong>Results: </strong>Two groups of hydrogels exhibited the appropriate viscosity, porosity, and degradation. The rate of cell proliferation on the 7^th day in the hydrogel with the peptide was the same as that of the control group. An <i>in vivo</i> test showed that the peptide-containing hydrogel significantly enhanced the regeneration process (<i>P</i>≤0.05). Tissue examination of the samples showed that the rate of angiogenesis and skin repair increased in the hydrogel with the peptide group. The use of peptides strengthened the repair processes in the skin area.</p><p><strong>Conclusion: </strong>These hydrogels represent a promising strategy to promote skin regeneration and provide a significant avenue for future clinical applications in regenerative medicine.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 3","pages":"412-422"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815286","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":"Quercetin improves ESAT-6-induced pleural mesothelial cell fibrosis by activating the Nrf2/HO-1 pathway.","authors":"Lina Chen, Zhou Yu, Zhuo Zhou, Bin Tian, Zhongfeng Huang, Yiju Cheng, Hai Long, Niwen Huang","doi":"10.22038/ijbms.2026.86824.18778","DOIUrl":"10.22038/ijbms.2026.86824.18778","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigated the mechanism by which quercetin suppresses oxidative stress and improves fibrosis in human pleural mesothelial cells (HPMCs) induced by the Mycobacterium tuberculosis-specific antigen early secretory antigen target protein-6 (ESAT-6) by activating the Nrf2/HO-1 signaling pathway, thereby suppressing oxidative stress.</p><p><strong>Materials and methods: </strong>An in vitro model of ESAT-6-induced HPMC fibrosis was established. The effects of various concentrations of quercetin on HPMCs were assessed using the CCK-8 assay. Markers of oxidative stress, such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH), were assessed. Immunofluorescence was utilized to detect levels of nuclear factor erythroid 2-related factor 2 (Nrf2), and western blot analysis was conducted to evaluate the protein levels of Nrf2, heme oxygenase-1 (HO-1), E-cadherin (E-cad), and α-smooth muscle actin (α-SMA).</p><p><strong>Results: </strong>Quercetin significantly improved ESAT-6-induced HPMC proliferation, reduced the oxidative stress marker MDA, and decreased the fibrosis marker α-SMA levels. It also promoted the translocation of Nrf2 into the nucleus in ESAT-6-induced pleural mesothelial cell fibrosis. Furthermore, quercetin enhanced the enzymatic activity of antioxidants, particularly GSH and SOD, and increased the expression levels of HO-1, Nrf2, and E-cad.</p><p><strong>Conclusion: </strong>The findings indicate that quercetin can inhibit oxidative stress by modulating the Nrf2 pathway and up-regulating HO-1 activity, thereby improving ESAT-6-induced pleural mesothelial cell fibrosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 5","pages":"730-735"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251100","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":"Antibody therapies in glioblastoma: Overcoming micro-environmental barriers.","authors":"Moeen Fuad Dababneh, Faris Anad Muhammad, Abdulkareem Shareef, S Renuka Jyothi, Ashish Singh Chauhan, Apurav Gautam, Lola Makhmudova, Hayder Naji Sameer, Ahmed Yaseen, Zainab H Athab, Mohaned Adil, Amirmohammad Khalifehsoltani, Reza Akhavan-Sigari","doi":"10.22038/ijbms.2026.90689.19548","DOIUrl":"10.22038/ijbms.2026.90689.19548","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains the most aggressive adult brain tumor, with median survival largely unchanged over two decades. Antibody-based therapies have shown promise in hematologic and systemic cancers, but translation to GBM has been hindered by the tumor's hostile microenvironment and immune evasion mechanisms. A structured literature search was conducted in PubMed, Scopus, Web of Science, and ClinicalTrials.gov for studies published between 2010 and 2025. Eligible publications included preclinical investigations, clinical trials, and reviews addressing antibody-based therapies, tumor microenvironmental barriers, and computational innovations. Data were synthesized into thematic categories: mechanisms of resistance, antibody-based platforms, nanotechnology-assisted delivery, and artificial intelligence (AI)-driven strategies. Antibody therapeutics including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and photoimmunotherapy show potential to enhance tumor targeting and immune activation. Key barriers such as the blood-brain barrier, immunosuppressive cell infiltration, and tumor heterogeneity significantly restrict efficacy. Novel approaches, including AI-enabled antibody design, digital twin modeling, and biomarker-driven patient stratification, offer opportunities to improve precision and overcome resistance. Combination strategies with radiotherapy, vaccines, or adoptive cell therapies further expand therapeutic potential. By reframing antibody therapy through the lens of barrier disarmament and technological integration, this review positions antibody-based approaches as realistic pillars of future GBM management. Strategic innovations in delivery, engineering, and computational modeling may transform antibodies from experimental tools into cornerstone therapies for this lethal malignancy.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 3","pages":"353-377"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815122","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}