Iranian Journal of Basic Medical Sciences最新文献

{"title":"The role of exosomes in brain tumors: Mechanisms, diagnosis, and therapeutic prospects.","authors":"Haider Falih Shamikh Al-Saedi, Waleed Khalid Younis Al-Bahadli, Waleed Murih Hatab, Arash Abdolmaleki","doi":"10.22038/ijbms.2025.88573.19183","DOIUrl":"10.22038/ijbms.2025.88573.19183","url":null,"abstract":"<p><p>Cancer remains a leading cause of mortality worldwide, with metastases significantly impacting patient prognosis. Brain metastases (BM) and primary malignant gliomas, such as glioblastoma (GBM), are among the most aggressive forms, with survival rates often below 12 months. GBM alone accounts for 2.5% of cancer-related deaths globally and is a leading cause of mortality in young adults aged 15-34. One of the major challenges in treating brain tumors is the blood-brain barrier (BBB), which limits the delivery of therapeutic agents to the central nervous system (CNS). Exosomes, a subset of extracellular vesicles (EVs), have emerged as promising candidates for overcoming these challenges due to their natural ability to transport bioactive molecules across biological barriers. These nanosized vesicles (30-150 nm) are actively involved in tumor progression, angiogenesis, immune modulation, and drug resistance. Recent studies have highlighted their potential as biomarkers for early cancer detection and as drug delivery vehicles capable of crossing the BBB. Despite their promise, challenges such as large-scale production, efficient cargo loading, and targeted delivery remain critical hurdles to clinical translation. This review explores the role of exosomes in brain malignancies, focusing on their involvement in tumor progression, potential utility as diagnostic biomarkers, and prospective therapeutic applications.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 3","pages":"313-321"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815266","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":"Ultrasound medicine in the era of precision theranostics: Mechanisms, molecular strategies, and clinical translation.","authors":"Lei Wang, Zhiyu Luo, Dan Liu","doi":"10.22038/ijbms.2026.90645.19532","DOIUrl":"10.22038/ijbms.2026.90645.19532","url":null,"abstract":"<p><p>Ultrasound (US) has evolved from a solely diagnostic tool into a multifaceted theranostics platform, proficient in both high-resolution imaging and tailored therapeutic intervention. Progress in acoustic physics, microbubble and nanobubble technology, and precision beam-forming has broadened its applications in cancer, neurology, cardiovascular diseases, and regenerative medicine. Notwithstanding these advancements, the translation into conventional clinical procedures is impeded by inadequate mapping of acoustic thresholds, variable safety factors, and insufficient integration with molecular and immunological targeting techniques, such as limited ligand specificity, off-target effects, and inconsistent activation of immune responses. This study consolidates the present knowledge of the mechanical, thermal, and sonochemical processes involved in US tissue interactions, focusing on controlled cavitation, bioheat transfer, and the formation of reactive oxygen species. We investigate novel molecular techniques, such as ultrasound-targeted drug delivery, gene therapy, immunomodulation, and sonodynamic treatment, emphasizing significant preclinical and clinical achievements. The exploration of cross-modality synergies, including magnetic resonance imaging, photoacoustic imaging, and nuclear medicine, demonstrates how US might enhance current diagnostic and therapeutic processes. Particular emphasis is centered on the tumor microenvironment, where US may influence immune cell migration, destroy stromal barriers, and augment the effectiveness of checkpoint inhibitors. In regenerative medicine, low-intensity pulsed ultrasound (LIPUS) is assessed for its function in mechanotransduction and tissue healing.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 4","pages":"498-521"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13213432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054243","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 role of oxidative stress in sleep deprivation-induced reproductive dysfunction: A rationale for anti-oxidant intervention.","authors":"Keke Chen, Kaixing Huang, Xiaoyu Liu, Fengyou Luo, Qiping Hu, Changlong Xu","doi":"10.22038/ijbms.2025.90559.19517","DOIUrl":"10.22038/ijbms.2025.90559.19517","url":null,"abstract":"<p><p>Sleep deprivation (SD) is a significant risk factor for reproductive dysfunction. This review aims to synthesize evidence establishing that oxidative stress (OS) is the key pathological mediator of SD-induced reproductive impairments in both sexes and to provide a comprehensive rationale for anti-oxidant intervention. We conducted a narrative review of peer-reviewed studies (2000-2025) from PubMed, ScienceDirect, Scopus, and Google Scholar. We examined the evidence linking SD, OS, and reproductive health, with a specific focus on recent preclinical and clinical studies that directly investigate the mechanistic role of OS and the efficacy of anti-oxidant therapies. The evidence demonstrates that SD induces systemic OS, which in turn drives reproductive pathology. In males, SD leads to increased testicular OS, resulting in impaired sperm quality and hormonal disruption. In females, SD is associated with diminished ovarian reserve and reduced oocyte quality, mediated by ovarian OS. Crucially, preclinical studies show that various anti-oxidants, including bromelain, vitamin C, and zinc, can successfully ameliorate SD-induced testicular damage. In women, clinical evidence links sleep disorders to lower melatonin levels in follicular fluid and decreased ovarian reserve, supporting a similar OS-mediated mechanism. The synthesized evidence strongly suggests that OS is a key pathological mechanism through which SD impairs reproductive function. This provides a strong scientific foundation for anti-oxidant therapies as a promising strategy to mitigate these harms. Future clinical trials are warranted to develop effective anti-oxidant regimens for individuals whose fertility is compromised by SD.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 2","pages":"191-201"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722965","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":"Potential role of ferroptosis in sterile acute lung injury induced by a non-hypoxic ischemia-reperfusion insult.","authors":"Farzaneh Kianian, Xiaoli Tian, Daisuke Maruyama, Arun Prakash","doi":"10.22038/ijbms.2026.92610.19992","DOIUrl":"10.22038/ijbms.2026.92610.19992","url":null,"abstract":"<p><strong>Objectives: </strong>Ferroptosis, a regulated form of necrotic cell death, is implicated in the pathogenesis of hypoxic lung ischemia-reperfusion injury (LIRI). However, its role in non-hypoxic LIRI, which occurs in common clinical conditions such as trauma and pulmonary embolism, remains unclear. Given that ferroptosis has been implicated in sterile inflammation and lipid peroxidation is a hallmark of this process, this study aimed to investigate the potential role of ferroptosis in inflammatory responses during non-hypoxic LIRI.</p><p><strong>Materials and methods: </strong>Non-hypoxic LIRI was induced in C57BL/6 mice by occluding the left pulmonary artery for 1 hr, followed by 30 min of reperfusion. The treatment group received liproxstatin-1 (Lip-1; 10 mg/kg, IP) 1 hr before surgery. IL-6 levels in plasma and lung tissue were measured by ELISA. For the <i>in vitro</i> model, normal human bronchial epithelial (NHBE) cells were exposed to nutritional ischemia for 1 hr and then reperfused for 2 hr. Cells were pretreated with Lip-1 (200 nM) 12 hr before ischemia. CXCL1 release was measured by ELISA, and lipid reactive oxygen species (ROS) accumulation was assessed by BODIPY 581/591 C11 fluorescence.</p><p><strong>Results: </strong>Non-hypoxic LIRI markedly increased IL-6 levels in plasma and lung tissue, as well as CXCL1 levels and lipid ROS accumulation in NHBE cells. Pretreatment with Lip-1 significantly reduced these inflammatory responses and lipid ROS accumulation compared with untreated LIRI.</p><p><strong>Conclusion: </strong>Our findings suggest that ferroptosis-associated lipid peroxidation is associated with sterile inflammatory responses during non-hypoxic LIRI in both systemic and epithelial compartments. Lip-1 attenuated these responses, highlighting a potential strategy for non-hypoxic LIRI.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 9","pages":"1355-1360"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900550","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":"Investigating the effects of taurine on Aβ-degradation proteins and neurogenesis-related genes in an LPS-induced neuroinflammatory SH-SY5Y cell model.","authors":"Pirouz Pourmohammad, Fereshteh Rahmati, Fatemeh Siadat, Sara Simorgh","doi":"10.22038/ijbms.2026.91521.19754","DOIUrl":"10.22038/ijbms.2026.91521.19754","url":null,"abstract":"<p><strong>Objectives: </strong>Taurine, a brain-abundant sulfonic acid, shows potential neuroprotective effects and may counter neurodegenerative processes. This study investigated the effects of taurine on neuroinflammation, focusing on Aβ-degrading proteins and gene expression related to neurogenesis in an LPS-stimulated SH-SY5Y cell model.</p><p><strong>Materials and methods: </strong>The effects of taurine (0.5 and 1 mg/ml) and LPS (0.5 and 10 μg/ml) on SH-SY5Y cell viability were assessed using the MTT assay. IL-1β and IL-6 expression was measured by real-time PCR, while matrix metalloproteinases (MMPs) and angiotensin-converting enzyme (ACE) levels were quantified via ELISA. Neurogenesis-related gene expression was evaluated using the Neurogenesis Plus RT² Profiler PCR array.</p><p><strong>Results: </strong>The MTT assay results demonstrated that taurine treatment at concentrations of 0.5 and 1 mg/ml significantly attenuated the cytotoxicity induced by LPS stimulation in SH-SY5Y cells. Also, treatment with taurine significantly reduced the expression levels of the inflammatory genes IL-1β and IL-6 in LPS-stimulated SH-SY5Y cells (<i>P</i><0.05). ELISA results further revealed that taurine treatment significantly increased the secretion levels of ACE and MMP-9 enzymes in LPS-stimulated SH-SY5Y cells (<i>P</i><0.05). LPS exposure in SH-SY5Y cells significantly up-regulated genes related to apoptosis, cell migration, and synaptic function (<i>P</i><0.005). Conversely, taurine treatment significantly increased the expression of genes involved in cell adhesion, synaptic function, growth factors, cytokines, differentiation, cell cycle, signaling, transcription, and cofactor activity (<i>P</i><0.005).</p><p><strong>Conclusion: </strong>These results suggest that taurine may act as a potential neuroprotective agent by increasing the secretion of MMP-9 and ACE, regulating neurogenesis-related genes, and reducing LPS-induced neuroinflammation.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 7","pages":"1043-1051"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874122","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":"Modulation of CCL5 and CXCR4 as EMT signaling biomarkers by cold atmospheric plasma and Anti-PD-1 combination therapy in melanoma: Insights from integrated bioinformatics and <i>in vitro</i> and <i>in vivo</i> validation.","authors":"Zeinab Rostami, Fatemeh Akhoundi, Zahra Yazdani, Mohammad Eslamijouybari, Mansooreh Mirzaei, Forouzan Bousaeedi, Ghazaleh Rostami, Alireza Rafiei","doi":"10.22038/ijbms.2026.91340.19707","DOIUrl":"10.22038/ijbms.2026.91340.19707","url":null,"abstract":"<p><strong>Objectives: </strong>Cold atmospheric plasma (CAP) has emerged as a promising non-thermal modality with anticancer effects. Combining CAP with immune checkpoint blockade (ICB) may enhance therapeutic efficacy, yet the molecular targets underlying this synergy remain incompletely understood.</p><p><strong>Materials and methods: </strong>Epithelial--mesenchymal transition (EMT)--associated genes responsive to CAP and Anti-PD-1 therapy were identified by integrating bioinformatics analyses of melanoma transcriptomic data with <i>in vitro</i> and <i>in vivo</i> experiments. Weighted gene co-expression network analysis (WGCNA), GO, and KEGG enrichment identified key modules and candidate genes. The effects of CAP, Anti-PD-1, and their combination on cell viability and gene expression were evaluated in B16F10 melanoma cells, L929 fibroblasts, and a syngeneic mouse melanoma model.</p><p><strong>Results: </strong>WGCNA highlighted CCL5 and CXCR4 as hub genes enriched in EMT-related pathways. MTT assays showed that CAP reduced B16F10 cell viability, an effect further enhanced by Anti-PD-1, while sparing L929 fibroblasts. In tumor-bearing mice, combination therapy produced the most pronounced tumor regression and down-regulation of CCL5 and CXCR4 compared with single treatments. Minimal viability or expression changes were observed in normal fibroblasts or untreated controls.</p><p><strong>Conclusion: </strong>CAP and Anti-PD-1 combination therapy effectively suppressed melanoma cell viability and modulated EMT-associated gene expression both <i>in vitro</i> and <i>in vivo</i>. We further explored a potential molecular mechanism underlying this therapeutic effect, revealing that the EMT-related genes CCL5 and CXCR4 play a vital role in this response. These findings highlight the relevance of these pathways and support the potential of combining CAP with ICB as a promising approach for melanoma treatment.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 7","pages":"1052-1065"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874133","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":"Non-coding RNAs related to PD1/PD-L1 signaling with potential diagnostic, prognostic, and therapeutic value in the tumorigenesis of brain cancers.","authors":"Reihane Behnam-Rassouli, Farzaneh Entezari, Majid Ghorbanzadeh, Ali Reyhani, Mohammadreza Nassiri, Fereshteh Golab, Farzad Rahmani","doi":"10.22038/ijbms.2026.94213.20304","DOIUrl":"10.22038/ijbms.2026.94213.20304","url":null,"abstract":"<p><p>Brain cancers are among the most aggressive malignancies associated with significant global morbidity and mortality. Cancer immunotherapy has emerged as a promising novel approach for the treatment of brain cancer through regulating the PD-1/PD-L1 signaling and disrupting tumor immune escape. Several targeted therapies have been developed to inhibit the PD-1/PD‑L1 route, but reduced therapeutic responses and drug resistance remain a major challenge that needs to be addressed. Notably, non-coding RNAs (ncRNAs), which include microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), exert crucial effects on cell proliferation, invasion, and immune escape in the tumor microenvironment (TME). It has been shown that ncRNAs reduce tumor formation and progression by regulating the PD-1/PD-L1 pathway and by down-regulating key transcription factors, including NF-κB, JAK, and STAT. Therefore, identifying novel regulatory ncRNAs and their associated target genes offers promising opportunities for developing therapeutic interventions against brain cancer. This review highlights recent advances in understanding the regulatory role of ncRNAs on the PD-1/ PD-L1 pathway in brain cancer tumorigenesis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 8","pages":"1174-1183"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864522","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":"Cordycepin ameliorates ischemia/reperfusion-induced acute kidney injury via inhibiting apoptosis and necroptosis.","authors":"Xiuzhao Fan, Xiutao Han, Zhibo Zhao, Junhu Li, Shuangshuang Tian, Fang Zhang, Xiaoshuang Zhou","doi":"10.22038/ijbms.2026.92098.19878","DOIUrl":"10.22038/ijbms.2026.92098.19878","url":null,"abstract":"<p><strong>Objectives: </strong>Cordycepin (COR) is a natural bioactive compound derived from <i>Cordyceps militaris</i>. Relevant studies have shown that COR can alleviate kidney damage, but the underlying mechanism of its action in the treatment of acute kidney injury (AKI) remains to be further clarified.</p><p><strong>Materials and methods: </strong>The GSE148420 dataset and GeneCards were used to identify AKI-related targets. GeneCards was used to obtain ischemia/reperfusion (I/R)-related targets. BATMAN 1.0 and GeneCards were used to identify potential drug targets of COR. Renal function, tissue damage, and molecular markers were assessed to explore the effects of COR on apoptosis and necroptosis in the treatment of AKI.</p><p><strong>Results: </strong>Network pharmacological analysis showed that AKI and COR shared 28 drug targets. Enrichment analysis showed that the targets were involved in signaling pathways, including apoptosis and necroptosis. <i>In vitro</i> experiments revealed that COR alleviated hypoxia/re-oxygenation(H/R)-induced HK-2 cells injury by reducing the expression of Bax and cleaved-Caspase3 while increasing the expression of Bcl-2. Necroptosis was lessened under COR treatment <i>in vitro</i> and in H/R-induced HK-2 cells by reducing the expression of RIPK1, RIPK3, MLKL, and p-MLKL. COR and Nec-1 (a RIPK1 inhibitor) had the same inhibitory effect, confirming the role of COR in alleviating AKI by inhibiting RIPK1-driven necroptosis. COR alleviated AKI by ameliorating renal morphology injury and pathological injury in vivo, manifested as a decrease in Scr and BUN levels, a significant reduction in the mRNA expression levels of <i>KIM-1</i> and NGAL, and a decrease in p-MLKL at the immunohistochemical level.</p><p><strong>Conclusion: </strong>COR may ameliorate I/R-induced AKI by inhibiting apoptosis and RIPK1/RIPK3/p-MLKL-mediated necroptosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 8","pages":"1218-1228"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864883","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":"Allele-specific disruption of KRAS p.G12V in colorectal cancer cells using electroporated Cas9 RNPs.","authors":"Firouzeh Morshedzadeh, Samaneh Sharif, Maryam Peymani, Malihe Lotfi, Mohammad Reza Abbaszadegan","doi":"10.22038/ijbms.2026.94681.20422","DOIUrl":"10.22038/ijbms.2026.94681.20422","url":null,"abstract":"<p><strong>Objectives: </strong>Colorectal cancer (CRC) is a major cause of mortality, and KRAS mutations drive tumorigenesis and therapy resistance. Although CRISPR-Cas9 enables precise genome editing, intracellular delivery of Cas9 ribonucleoproteins (RNPs) remains challenging. We evaluated direct electroporation of Cas9-sgRNA RNPs targeting KRAS p.G12V in SW480 CRC cells to assess delivery efficiency, on-target editing, off-target activity, and viability effects.</p><p><strong>Materials and methods: </strong>An sgRNA targeting KRAS p.G12V was designed computationally. Cas9-sgRNA RNPs were assembled and validated by <i>in vitro</i> digestion. RNPs were electroporated into SW480 cells using a square-wave electroporation protocol; pmaxGFP served as the delivery control. On-target editing and five predicted off-target loci were assessed by Sanger sequencing and TIDE analysis. Cell viability was measured by the MTT assay.</p><p><strong>Results: </strong>Electroporation resulted in high GFP expression (~97%). TIDE analysis at the KRAS locus estimated ~27% total indels. Cells treated with KRAS-targeting RNPs exhibited significantly reduced viability compared with controls (<i>P</i><0.05). No detectable indels were observed at the five off-target sites. While supporting feasibility, deeper sequencing and mechanistic analyses are needed to confirm specificity.</p><p><strong>Conclusion: </strong>Direct electroporation of Cas9-sgRNA RNPs enabled efficient intracellular delivery and targeted disruption in SW480 cells, reducing viability without detectable editing at selected off-target loci. This approach is practical for KRAS-targeted studies in CRC and warrants further investigation. Direct electroporation of Cas9--sgRNA RNPs enabled efficient delivery in SW480 cells, accompanied by reduced viability, with no detectable editing at selected off-target candidates by Sanger/TIDE. These findings support RNP electroporation as a practical approach for KRAS-targeted studies in CRC and justify follow-up with amplicon deep sequencing and additional cell models.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 8","pages":"1278-1285"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864952","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":"Efficacy of finerenone and/or roflumilast in alleviation of intestinal ischemic reperfusion injury via regulation of IL10/AMPK/VEGF/eNOS pathway in rats.","authors":"Marwa Monier Mahmoud Refaie, Randa Ahmed Ibrahim, Sayed Shehata, Asmaa A Muhammed, Shereen Mohammed Mohammed Elsaghir, Asmaa S M Abdel Fattah, Asmaa A Hasan, Amany H Abdel Naiem, Nagwa Zenhom Mustafa Ahmed, Mohamed Rabie Saad, Doaa Mohamed Elroby Ali, Heba A Habib, Nardien Ekram Haliem Saleh","doi":"10.22038/ijbms.2026.94574.20397","DOIUrl":"10.22038/ijbms.2026.94574.20397","url":null,"abstract":"<p><strong>Objectives: </strong>Intestinal ischemia is a serious emergency that requires immediate management and surgical intervention. Finding an effective therapeutic strategy, in addition to surgical treatment, is essential to mitigate the harmful effects of intestinal ischemia-reperfusion (IIR)-induced tissue injury not only in the intestine itself but also in distant organs, especially the liver. This prompted us to evaluate, for the first time, the role of finerenone (FIN), a non-steroidal selective mineralocorticoid receptor antagonist, and/or roflumilast (ROF), a selective phosphodiesterase 4 inhibitor, in experimentally induced IIR injury in both hepatic and intestinal tissues, with a detailed study of various mechanisms.</p><p><strong>Materials and methods: </strong>Wistar rats were randomly assigned to 5 groups (N=10): Sham group, IIR group, FIN/ROF, FIN, and ROF-administered groups, with IIR induction.</p><p><strong>Results: </strong>Interestingly, FIN/ROF significantly reduced elevated levels of liver function enzymes, tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), caspase-3 expression, and aldosterone. Furthermore, FIN/ROF could normalize the tissue level of interleukin 10 (IL-10), adenosine monophosphate-activated protein kinase (AMPK), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), antioxidant parameters, reduced glutathione (GSH), and total antioxidant capacity (TAC) with remarkable improvement in the histopathological features.</p><p><strong>Conclusion: </strong>FIN/ROF could mitigate IIR-induced hepatic and intestinal damage via FIN-mediated blockade of mineralocorticoid receptors and ROF-mediated inhibition of phosphodiesterase 4, and through antioxidant, anti-apoptotic, and anti-inflammatory properties with regulation of the IL-10/AMPK/VEGF/eNOS pathway. Thus, FIN/ROF is a potential medical treatment for IIR, in addition to surgery.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 10","pages":"1535-1546"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038572","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}