Iranian Journal of Basic Medical Sciences最新文献

{"title":"Comparative analysis of second and third-generation nanobody-based CAR-NK cells targeting PSMA in prostate cancer immunotherapy: <i>In silico</i> and <i>in vitro</i> studies.","authors":"Masoud Gandomkar Ghalhar, Arezoo Karami Vandishi, Akram Ramazani, Fatemeh Hajari Taheri, Zahra Sharifzadeh, Mohsen Abolhassani, Masoud Soleimani, Niloofar Taghipour, Wytske M van Weerden, Mojgan Bandehpour, Mahmoud Hassani, Kowsar Bagherzadeh","doi":"10.22038/ijbms.2026.92122.19891","DOIUrl":"10.22038/ijbms.2026.92122.19891","url":null,"abstract":"<p><strong>Objectives: </strong>The use of CAR technology in the treatment of cancer cells is progressing, as well as the use of CAR T-cell in the treatment of blood malignancies is in the clinical trial stage. In this study, have compared the second and third generation CAR expressed in NK cells in dealing with prostate cancer cells.</p><p><strong>Materials and methods: </strong>To optimize the CAR design for detection of NK-92 cells, an <i>in silico</i> approach to select between two tags (Flag and c-Myc tags) was initially employed, ultimately favoring the Flag tag. By using lentiviral particles, transduced NK-92 cells with second- and third-generation CAR constructs were subsequently tested as effector cells against prostate cancer cells expressing the Prostate-Specific Membrane Antigen (PSMA). Then assessed both cytokine secretion and cytotoxic responses.</p><p><strong>Results: </strong>Computational analysis indicated that the NB/Flag/hinge configuration would provide superior PSMA recognition. Flow cytometry confirmed successful CAR expression in 47% of second-generation and 49% of third-generation NK-92 cells. Upon co-culture with PSMA-positive LNCaP cells and PSMA-negative PC-3 cells, the third-generation CAR NK cells demonstrated a noticeably stronger cytotoxic effect. Furthermore, higher levels of IL-2, TNF-α, and IFN-γ secretion were observed in the third-generation CAR group compared to the second.</p><p><strong>Conclusion: </strong>According to the computational studies, NB/Flag/hinge interacts with PSMA primarily through electrostatic forces. More importantly, third-generation CAR NK cells targeting PSMA displayed enhanced cytotoxicity and cytokine production relative to second-generation counterparts, pointing to their greater potential for therapeutic application.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 7","pages":"1122-1130"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874104","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":"A lipid metabolism-based gene signature defines diagnosis and molecular heterogeneity in diabetic nephropathy.","authors":"Qingbu Mei, Xinyu Liu, Jing Xu, Shuang Li, Tao Wang, Hui Yuan","doi":"10.22038/ijbms.2026.94356.20339","DOIUrl":"10.22038/ijbms.2026.94356.20339","url":null,"abstract":"<p><strong>Objectives: </strong>To identify lipid metabolism-related biomarkers of diabetic nephropathy (DN), develop and validate a diagnostic model, and further explore immune infiltration patterns and molecular subtypes of DN.</p><p><strong>Materials and methods: </strong>Multiple public transcriptomic datasets were integrated to identify lipid metabolism-related biomarkers for DN using differential expression analysis, weighted gene co-expression network analysis, and machine learning. A diagnostic model was then constructed from these biomarkers, and its performance was evaluated using ROC curve and nomogram analyses, followed by validation in an independent cohort. In addition, immune cell infiltration was assessed with the CIBERSORT algorithm, and consensus clustering identified molecular subtypes of DN. Finally, the findings were validated in a model of type 2 diabetes.</p><p><strong>Results: </strong>A total of 28 lipid metabolism-related differentially expressed genes were identified, and five hub biomarkers (G0S2, PTGDS, CA2, CYP27B1, and HSD17B14) were screened and demonstrated favorable diagnostic performance in both training and validation cohorts. Functional enrichment analysis revealed that these genes were mainly involved in fatty acid metabolism and PPAR signaling pathways. Immune infiltration analysis revealed significant correlations between dysregulated lipid metabolism and immune cell infiltration in DN. Consensus clustering identified distinct molecular subtypes of DN with different lipid metabolic characteristics. Critically, bioinformatic predictions were validated in db/db mice, showing significantly elevated mRNA and protein levels of all five biomarkers in DN kidneys.</p><p><strong>Conclusion: </strong>Our findings reveal a validated lipid-metabolism-based diagnostic signature with potential for early detection, molecular stratification, and mechanistic investigation.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 10","pages":"1510-1520"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038641","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":"Acute and chronic zolpidem administration changes hippocampal long-term potentiation (LTP) as a possible mechanism of memory impairment.","authors":"Zahra Rezaeiasl, Mahmoud Salami, Hamid Reza Banafshe","doi":"10.22038/ijbms.2026.95516.20587","DOIUrl":"10.22038/ijbms.2026.95516.20587","url":null,"abstract":"<p><strong>Objectives: </strong>Zolpidem is a non-benzodiazepine GABAA receptor positive modulator commonly used to treat short-term insomnia. Given its widespread use, understanding its potential impact on cognitive function and synaptic mechanisms is of great interest. This study aimed to investigate the effects of acute and chronic zolpidem administration on hippocampal long-term potentiation (LTP) as a possible mechanism underlying memory impairment in rats.</p><p><strong>Materials and methods: </strong>Three groups of rats were used in this study: control, acute (received a single dose of zolpidem, 15 mg/kg), and chronic (received daily doses of zolpidem, 15 mg/kg, for 30 consecutive days). Spatial learning and memory were assessed using the Morris water maze. Basic synaptic transmission and LTP were assessed by recording field excitatory postsynaptic potentials in the hippocampus.</p><p><strong>Results: </strong>No significant differences were observed in spatial learning among the groups. However, evaluation of spatial memory showed that acute and chronic treatment significantly impaired memory performance compared to the control group. Spatial memory was more severely impaired in the chronic group than in the acute group. Electrophysiological data showed that although LTP was induced in both acute and chronic treatment groups, both had significantly lower LTP magnitude than the control group.</p><p><strong>Conclusion: </strong>Chronic zolpidem administration caused significantly greater impairment of spatial memory than acute administration, whereas LTP induction was similarly reduced in both groups. These findings suggest that long-term zolpidem use may pose a greater risk to cognitive function than acute exposure.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 11","pages":"1670-1676"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215807","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":"Evaluation of cytotoxic, anti-oxidant, and apoptotic effects of <i>Dysphania botrys</i> extract on B16F10 and MCF-7 cell lines.","authors":"Fatemeh Forouzanfar, Elham Ramazani, Mohammad Esmaeili, Seyed Ahmad Emami, Zahra Tayarani-Najaran","doi":"10.22038/ijbms.2025.87553.18912","DOIUrl":"10.22038/ijbms.2025.87553.18912","url":null,"abstract":"<p><strong>Objectives: </strong><i>Dysphania botrys</i> (L.) Mosyakin & Clemants (Basionym: <i>Chenopodium botrys</i> L.), belonging to the Amaranthaceae family, has been used for the treatment of inflammation, bacterial and viral infections, and diabetes. In this study, we aimed to evaluate the potential cytotoxic, anti-oxidant, and apoptotic activities of methanol (MeOH) extract and petroleum ether (PE) and dichloromethane (DCM) fractions of <i>D. botrys</i> against B16F10 and MCF-7 cell lines.</p><p><strong>Materials and methods: </strong>The anti-oxidant activities of fractions were measured using FRAP, DPPH, and β-carotene assays. The cytotoxicity of extracts and the intracellular ROS content were assessed using resazurin and DCFH-DA assays, respectively. A flow cytometry assay using PI staining was performed to measure the apoptotic activity of the fractions. Total phenolic and flavonoid content was determined using spectrophotometric methods.</p><p><strong>Results: </strong>The DCM fraction of <i>D. botrys</i> exhibited the highest anti-oxidant activity in FRAP, DPPH, and β-carotene assays, which also showed the highest amount of phenolic and flavonoid content compared to the MeOH extract and PE fraction. Cell viability and intracellular ROS content were significantly decreased following the treatment of B16F10 and MCF-7 cells with 100 and 200 µg/ml DCM and PE fractions. Treatment with 200 µg/ml DCM and PE fractions increased apoptosis in B16F10 cells.</p><p><strong>Conclusion: </strong>DCM fraction of <i>D. botrys</i> had significant anti-oxidant effects that may be associated with its phenolic and flavonoid compounds. It seems that terpenoid compounds are responsible for cytotoxic effects. Hence, complementary studies are needed to assess other bioactive compounds of <i>D. botrys</i> and their protective mechanisms.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"19 1","pages":"74-80"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118753","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":"Ashwagandha (<i>Withania somnifera</i>) in insulin resistance and metabolic syndrome: A literature review on mechanisms.","authors":"Emad Azimi, Maryam Rameshrad, Mahboobeh Ghasemzadeh Rahbardar, Hossein Hosseinzadeh","doi":"10.22038/ijbms.2025.86747.18741","DOIUrl":"10.22038/ijbms.2025.86747.18741","url":null,"abstract":"<p><p>Metabolic syndrome is characterized by obesity, insulin resistance, dyslipidemia, and hypertension. <i>Withania somnifer</i>a, commonly known as ashwagandha or Indian winter cherry, belongs to the <i>Solanaceae</i> family. <i>W. somnifera</i>, particularly its powdered root, is a fundamental component of traditional Indian medicine. <i>W. somnifera</i> (Ashwagandha) exhibits pharmacological activities, including immunomodulatory, anti-stress, and neuroprotective effects in animal models. Also, preclinical and clinical studies demonstrate its anti-inflammatory and antiviral properties. In rodent studies, ashwagandha regulates apoptosis and modulates reactive oxygen species (ROS) levels as well as mitochondrial activity. Additionally, it improves endothelial function in rats, dogs, and human brain endothelial cells. Research conducted in both living organisms and controlled laboratory conditions has demonstrated that <i>W. somnifera</i> alleviates the symptoms of metabolic syndrome. It positively affects diabetes by inhibiting dipeptidyl peptidase-4 (DPP-4), α-glucosidase, and α-amylase, while simultaneously increasing pancreatic insulin secretion and improving insulin sensitivity in organs. It has a vasodilatory and diuretic effect. Ashwagandha reduces the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. It modulates the gene expression of peroxisome proliferator-activated receptor (PPAR)-γ. It regulates the gene expression of sterol regulatory element-binding protein (SREBP)-1c and <i>CYP7A1</i>. It increases the secretion of bile acids that eliminate excess cholesterol. It reduces oxidative stress and inflammation while protecting the body from the harmful effects of elevated cholesterol. This study aims to compile a variety of research findings on the effectiveness of ashwagandha in managing metabolic syndrome.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 1","pages":"3-21"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118859","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":"HIPK2 protects neurons from oxidative stress and modulates central nervous system responses following traumatic brain injury.","authors":"Qiangbin Zhu, Fan Wang, Bojun Zhang, Zhigang Pan, Xiaodong Kang, Weipeng Hu","doi":"10.22038/ijbms.2026.90522.19511","DOIUrl":"10.22038/ijbms.2026.90522.19511","url":null,"abstract":"<p><strong>Objectives: </strong>Traumatic brain injury (TBI) induces oxidative stress, contributing to secondary neuronal damage. This study aimed to elucidate the role of the stress-responsive kinase HIPK2 in regulating endogenous antioxidant defenses in neural tissue following TBI.</p><p><strong>Materials and methods: </strong>We employed complementary <i>in vitro</i> and <i>in vivo</i> models: an H₂O₂-induced oxidative stress model in PC12 cells (with HIPK2 inhibited by tBID) and a controlled cortical impact mouse model of TBI (with HIPK2 overexpressed via intracerebroventricular Ad-HIPK2 injection). Analyses included assessments of cell viability, mRNA expression, and protein levels of key antioxidant factors (HO-1, UGT1A1, NQO1).</p><p><strong>Results: </strong><i>In vitro</i>, HIPK2 inhibition markedly increased oxidative stress-induced cell death and significantly down-regulated UGT1A1 expression. <i>In vivo</i>, endogenous HIPK2 expression was significantly suppressed post-TBI. Conversely, HIPK2 overexpression effectively rescued the expression of antioxidant proteins UGT1A1 and NQO1.</p><p><strong>Conclusion: </strong>These results demonstrate that HIPK2 is a critical modulator of the antioxidant response after TBI, capable of orchestrating key defense genes and conferring neuroprotection. Our findings identify HIPK2 as a promising molecular target for therapeutic intervention against TBI-related oxidative damage.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 5","pages":"804-811"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251622","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":"Down-regulation of AGXT2L1 promotes the development of nonalcoholic fatty liver disease.","authors":"Yue Yu, Lu Wu","doi":"10.22038/ijbms.2026.89567.19546","DOIUrl":"10.22038/ijbms.2026.89567.19546","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of alanine-glyoxylate aminotransferase 2-like1 (AGXT2L1) in Nonalcoholic fatty liver disease (NAFLD) and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Changes in AGXT2L1 expression during NASH progression were analyzed using tissue samples, cell experiments, and animal models. RNA sequencing was performed on experimental mice to explore potential mechanisms by assessing inflammatory factors, cell apoptosis, and endoplasmic reticulum stress.</p><p><strong>Results: </strong>Compared with normal tissues, AGXT2L1 expression was reduced in multiple liver diseases. Both <i>in vitro</i> and <i>in vivo</i> experiments confirmed that down-regulation of AGXT2L1 exacerbated NASH severity. RNA sequencing initially indicated that abnormal AGXT2L1 expression primarily affects phospholipid metabolism. Additionally, animal experiments showed that AGXT2L1 deficiency increased the number of apoptotic hepatocytes and elevated the expression of endoplasmic reticulum stress markers.</p><p><strong>Conclusion: </strong>Decreased AGXT2L1 expression is an evident alteration in liver injury. It has been indicated that down-regulation of AGXT2L1 promotes NAFLD development, possibly through three pathways: activation of inflammatory responses, promotion of hepatocyte apoptosis, and enhancement of endoplasmic reticulum stress.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 9","pages":"1390-1397"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900244","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":"Electroacupuncture ameliorates diabetic renal injury by regulating the AMPK-autophagy signaling pathway.","authors":"Zehao Zhang, Meijuan Xiang, Lejian Lan, Duo Peng, Lixia You, Mengmeng Jia, Jianyun Peng","doi":"10.22038/ijbms.2026.93505.20169","DOIUrl":"10.22038/ijbms.2026.93505.20169","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and the leading cause of end-stage renal disease worldwide. Despite evidence supporting the renoprotective effects of electroacupuncture (EA), the underpinning molecular mechanisms require further investigation. This study was designed to evaluate the therapeutic efficacy of EA in mice with DN and to elucidate its potential mechanisms of action.</p><p><strong>Materials and methods: </strong>A DN model was established in male C57BL/6 mice by streptozotocin (STZ) injection and validated. Mice were randomly allocated into four groups: control, normal+electroacupuncture (EA), DN, and DN+EA. EA was applied at Yanglingquan and Zusanli acupoints in the treatment groups. Renal histology and ultrastructure were examined. AMPK and downstream autophagy-related molecule expression were analyzed by qRT-PCR and Western blot.</p><p><strong>Results: </strong>Renal tissues from DN mice exhibited suppressed autophagy, marked by decreased microtubule-associated protein 1 light chain 3-II (LC3-II) and increased Sequestosome-1 (p62) expression, along with reduced phosphorylation of AMP-activated protein kinase (AMPK) and Unc-51 Like Autophagy Activating Kinase 1(ULK1) and increased Phosphorylated mammalian target of rapamycin (p-mTOR) levels after 8 weeks, indicating impaired autophagy and renal injury. EA treatment reversed these alterations by enhancing AMPK and ULK1 phosphorylation, restoring autophagy, and mitigating renal damage.</p><p><strong>Conclusion: </strong>The AMPK signaling pathway represents a novel therapeutic target for DN. Our data indicate that EA facilitates renal protection by activating AMPK/ULK1-mediated autophagy, implicating EA as a viable strategy for targeting this pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 9","pages":"1424-1432"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900542","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":"Impact of TGF-β and ERK1/2 inhibition on preimplantation embryo development and quality.","authors":"Faezeh Mohammadi Ghazani, Fatemeh Shirvanizadeh, Seyedeh-Nafiseh Hassani, Azam Dalman, Nahid Nasiri, Maryam Zarei, Saman Maroufizadeh, Poopak Eftekhari-Yazdi","doi":"10.22038/ijbms.2026.89761.19359","DOIUrl":"10.22038/ijbms.2026.89761.19359","url":null,"abstract":"<p><strong>Objectives: </strong>Preimplantation embryo culture is a critical phase in assisted reproductive technologies. The use of small molecules to modulate signaling pathways has emerged as a strategy to improve embryo viability. SB431542 inhibits the TGF-β pathway, while PD0325901 inhibits the MEK/ERK pathway. This study investigates whether their combined application affects embryonic development and cellular composition during early culture, independent of stem cell derivation.</p><p><strong>Materials and methods: </strong>To assess the effects of SB431542 and PD0325901 on early embryo development, mouse embryos at 2PN, two-cell, and eight-cell stages were collected <i>in vivo</i> and cultured in LIF-supplemented medium containing both molecules until the blastocyst stage. Embryo quality, apoptosis, and developmental progression were assessed using differential staining, TUNEL assay, and continuous monitoring throughout the culture period.</p><p><strong>Results: </strong>Embryos treated with SB431542 and PD0325901 showed a slightly higher rate of blastocyst formation than controls, though the difference was not statistically significant. Degeneration and apoptosis rates were also comparable between groups. However, treated embryos exhibited a significant reduction in ICM cells at early stages, suggesting compromised inner cell mass development. These findings indicate that dual inhibition may not enhance embryo quality under the tested conditions.</p><p><strong>Conclusion: </strong>SB431542 and PD0325901, when applied during preimplantation embryo culture, do not significantly improve developmental progression or reduce degeneration and apoptosis. The observed decrease in ICM cells suggests limited benefit for embryo culture protocols designed to support early development. Further studies are needed to evaluate their relevance in stem cell derivation contexts.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 4","pages":"578-589"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054289","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":"Protocatechuic acid mitigates diazinon-induced lung injury in rats through modulation of oxidative stress, inflammatory, Keap-1/Nrf-2/HO-1 and ER stress-mediated apoptotic pathways.","authors":"Tuba Karaarslan, Omercan Alat, Ismail Can, Esra Aktas Senocak, Cihan Gur, Ilyas Bozkurt, Mohammad Alhilal, Mesut Bunyami Halici","doi":"10.22038/ijbms.2025.90102.19424","DOIUrl":"10.22038/ijbms.2025.90102.19424","url":null,"abstract":"<p><strong>Objectives: </strong>Diazinon (DZN), a widely used organophosphate pesticide, induces pulmonary toxicity through oxidative stress, inflammation, endoplasmic reticulum (ER) stress, and apoptosis. This study investigated the potential protective effects of protocatechuic acid (PCA) against DZN-induced lung injury in rats.</p><p><strong>Materials and methods: </strong>Thirty-five adult rats were randomly assigned to five groups (n = 7): Control, DZN (20 mg/kg), PCA100 (100 mg/kg), DZN + PCA50, and DZN + PCA100. Lung tissues were evaluated histopathologically, and oxidative stress markers (GSH, SOD, CAT, and GPx) and inflammatory mediators (TNF-α, IL-1β, IL-6, NF-κB, COX-2, and iNOS) were measured by ELISA. The protein levels of Keap-1, Nrf2, and HO-1 were assessed via Western blotting. Expression of ER stress-related genes (XBP-1, eIF2, ATF4, CHOP) and apoptotic markers (Bax, Bcl-2, caspase-3, -6, -9) was analyzed by qRT-PCR.</p><p><strong>Results: </strong>DZN exposure caused severe histopathological damage and significantly increased oxidative, inflammatory, ER stress, and apoptotic responses. PCA administration, particularly at 100 mg/kg, markedly improved lung morphology, normalized antioxidant enzyme levels, reduced cytokine production and NF-κB activation, and downregulated ER stress and apoptosis-related genes. PCA also enhanced Bcl-2 expression and activated the Nrf2/HO-1 signaling pathway.</p><p><strong>Conclusion: </strong>PCA exerts dose-dependent protective effects against DZN-induced pulmonary toxicity by modulating oxidative stress, inflammation, ER stress, and apoptosis. These findings suggest that PCA may serve as a promising therapeutic candidate for mitigating pesticide-related lung injury.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 2","pages":"261-270"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722938","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}