Iranian Journal of Basic Medical Sciences最新文献

{"title":"Synthesis, radiolabeling, and biodistribution evaluation of novel hyperbranched polyglycerols-based radiotracers for targeting PSMA in prostate cancer.","authors":"Sara Roustaei, Mehdi Akhlaghi, Safura Jokar, Omid Bavi, Mehdi Shafiee Ardestani, Khosrou Abdi, Mona Mosayebnia, Mahboobeh Asadi, Zahra Ghiamaty, Mahshid Kiani, Davood Beiki","doi":"10.22038/ijbms.2026.94567.20396","DOIUrl":"10.22038/ijbms.2026.94567.20396","url":null,"abstract":"<p><strong>Objectives: </strong>Prostate-specific membrane antigen (PSMA) is a valuable target for prostate cancer imaging and therapy. This study aimed to improve the rapid blood clearance and suboptimal tumor uptake and retention of radiolabeled PSMA by developing a hyperbranched polyglycerol (HPG)-based PSMA conjugate.</p><p><strong>Materials and methods: </strong>HPG was synthesized via a one-step ring-opening multibranching polymerization (ROMBP) technique and sequentially functionalized with a PSMA-targeting ligand and a tris (hydroxypyridinone) (THP) chelator. The final construct was radiolabeled with gallium-68 or technetium-99m. Physicochemical properties, including lipophilicity (log P) and <i>in vitro</i> stability, were evaluated. <i>In vivo</i> biodistribution and imaging were assessed in LNCaP tumor-bearing nude mice using PET/SPECT/CT.</p><p><strong>Results: </strong>The THP-HPGs-PSMA derivative (170 kDa, 5-6 PSMA ligands, and 7-8 THP chelators per polymer molecule) achieved radiochemical purity >99%. [⁶⁸Ga]Ga THP HPG PSMA had high stability (>95% after 120 min), and log P of -1.56 ± 0.18. Blood uptake was 13.95 ± 0.75 and 11.82 ± 0.88 %ID/g at 30 and 120 min, respectively. Tumor uptake reached 7.12 ± 0.27, 7.40 ± 0.63, and 7.91 ± 0.20 %ID/g at 30, 60, and 120 min, respectively. Clearance was predominantly hepatobiliary with reduced renal excretion. [^99mTc]Tc-THP-HPG-PSMA showed tumor uptake of 8.74 ± 0.25, 9.41 ± 0.42, and 9.80 ± 0.41 %ID/g at 4, 8, and 16 hr. Blocking studies reduced tumor uptake from 7.12 ± 0.27 to 0.93 ± 0.53 %ID/g.</p><p><strong>Conclusion: </strong>Radiolabeled THP-HPG-PSMA demonstrates improved pharmacokinetics, enhanced tumor uptake, prolonged tumor retention, and favorable tumor-to-blood ratios, indicating strong potential for PSMA-targeted prostate cancer applications.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 7","pages":"1089-1099"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874065","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":"Trigonelline protects against alcohol-induced brain damage by inhibition of oxidative stress, TLR4/NF-κB/proinflammatory cytokines pathway, and apoptosis.","authors":"Keyvan Amirshahrokhi, Ali Niapour, Mahsa Imani","doi":"10.22038/ijbms.2026.94209.20306","DOIUrl":"10.22038/ijbms.2026.94209.20306","url":null,"abstract":"<p><strong>Objectives: </strong>Brain injury is one of the most predominant complications following excessive alcohol consumption. Oxidative, inflammatory, and apoptotic processes are the essential mechanisms involved in alcohol-induced brain damage. Trigonelline is a natural compound that has a variety of pharmacologic activities. The present study investigated the protective effect of trigonelline in alcohol-induced brain injury and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Adult male mice (C57BL/6) were exposed to binge ethanol (6 g/kg/day, by gavage) and treated with trigonelline (50 and 100 mg/kg/day, orally) for 6 days. Mice were sacrificed and the brain tissues were dissected for experimental assessments.</p><p><strong>Results: </strong>The results showed that trigonelline alleviated alcohol-induced locomotor impairment and brain oxidative damage by decreasing lipid peroxidation and protein oxidation. Trigonelline restored the levels of protective antioxidants (GSH, SOD, and HO-1) and reduced the levels of ICAM-1 and MPO in the brains of mice exposed to alcohol. Trigonelline significantly reduced alcohol-induced brain inflammation by the inhibition of iNOS/NO, TLR4, NF-κB, and proinflammatory cytokines (TNF-α, IL-6, IL-1β, and TGF-β1). Moreover, trigonelline treatment reduced the levels of caspase-3, cytochrome c, and TUNEL positive cells in the brains of alcohol-exposed mice.</p><p><strong>Conclusion: </strong>These findings suggest that trigonelline protects brain against alcohol intoxication by inhibition of oxidative and inflammatory and apoptotic responses. Therefore, trigonelline may serve as a potential therapeutic approach for the protection of brain damage associated with binge alcohol consumption.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 7","pages":"1079-1088"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874047","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 efficacy of thymol in testicular ischemia/reperfusion injury in rats: A biochemical and histopathological evaluation.","authors":"Ahmet Mentese, Ilke Onur Kazaz, Zeynep Sagnak Yilmaz, Nihal Turkmen Alemdar, Elif Ayazoglu Demir, Fatih Colak, Selim Demir","doi":"10.22038/ijbms.2026.91992.19847","DOIUrl":"10.22038/ijbms.2026.91992.19847","url":null,"abstract":"<p><strong>Objectives: </strong>Testicular torsion represents a critical urological emergency, characterised by the rotation of the testicle around the spermatic cord and the only treatment option to prevent testicular loss is detorsion. Testicular ischemia/reperfusion injury (IRI) may result from ischemia due to torsion and reperfusion due to detorsion, which cause injury as a result of the loss of blood flow to the testicular tissue. Thymol (THY), known for its antioxidant properties, is a phenolic monoterpenoid used in the cosmetic and agricultural industries. The objective of this study was to evaluate the hypothesis that THY can safeguard the testicular tissue in a rat model of testicular IRI.</p><p><strong>Materials and methods: </strong>Eighteen Wistar-Albino rats were randomly divided into 3 groups: control, IRI, and IRI+THY (100 mg/kg). In order to create the IRI model, a four-hour period of ischemia was initiated by rotating the left testis 720°, which was then followed by a two-hour period of reperfusion. The rats were sacrificed at the six-hour mark, after which biochemical and histopathological analyses were conducted on the excised testicular tissues.</p><p><strong>Results: </strong>THY treatment resulted in a notable improvement in testicular damage, as evidenced by the reduction of IRI-induced histopathological findings and an increase in Johnsen scores. In addition, THY treatment led to a significant decrease in the levels of biomarkers associated with IRI-induced inflammation, oxidative stress and endoplasmic reticulum stress.</p><p><strong>Conclusion: </strong>These initial preclinical findings indicate that THY may confer protection against testicular damage induced by IRI. However, further comprehensive studies are required to substantiate this effect.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 7","pages":"1115-1121"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874124","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 differentiation of the umbilical cord blood-derived mesenchymal stem cells into male germ-line cells in two-dimensional and three-dimensional scaffolds containing naringin.","authors":"Arian Azimi, Arian Ehterami, Sepehr Zamani, Seyede Nazanin Aghayan, Seyed Meysam Yekesadat, Fariborz Sharifianjazi, Sina Sohrabi, Morteza Alizadeh, Majid Salehi","doi":"10.22038/ijbms.2026.88928.19199","DOIUrl":"10.22038/ijbms.2026.88928.19199","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the differentiation potential of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) into male germ-like cells using a three-dimensional poly (L-lactic acid)/gelatin nanofiber (PLLA/GNF) scaffold incorporated with naringin (Nar).</p><p><strong>Materials and methods: </strong>The composite scaffold was fabricated by freeze-drying a PLLA solution containing 1% Nar and electrospun GNFs. Scaffold characterization included morphological analysis, porosity assessment, drug release profiling, and biodegradation testing. UCB-MSCs were isolated and characterized for surface markers (CD44⁺/CD90⁺/CD34⁻/CD45⁻) via flow cytometry. Cells were seeded onto scaffolds and differentiated using BMP4 (25 ng/ml) alone or in combination with retinoic acid (10⁻⁶ M). Evaluations included the MTT assay for viability, immunofluorescence for germ cell markers (PLZF, DAZL, OCT4), and <i>in vivo</i> biocompatibility assessed by subcutaneous implantation in rat models.</p><p><strong>Results: </strong>The scaffold demonstrated optimal physical properties, with a porosity of 81.13 ± 2.22% and an average pore size of 108.31 ± 9.29 μm. Nar release profile showed sustained delivery with cumulative release of 38.5 ± 5.72% over 14 days. Biodegradation rate reached 51.07 ± 5.64% after 14 days. MTT assay revealed significantly enhanced cell proliferation in Nar-containing scaffolds at both 24 and 72 hr (<i>P</i>< 0.05). Immunofluorescence analysis demonstrated markedly higher expression of germ cell markers in 3D cultures compared to 2D controls. In vivo evaluation confirmed excellent biocompatibility with minimal inflammatory response.</p><p><strong>Conclusion: </strong>The 3D PLLA/GNF/Nar scaffold creates a favorable microenvironment that effectively promotes UCB-MSC differentiation into male germ-like cells, representing a promising platform for reproductive tissue engineering applications.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 2","pages":"249-260"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722759","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":"Neuroprotective effects of kojic acid and nano-kojic acid in experimental brain ischemia induced by bilateral common carotid artery occlusion.","authors":"Mohammad Shokati Sayyad, Majid Saeedi, Fatemeh Shaki, Fereshteh Talebpour Amiri, Reza Negarandeh, Mohammad Seyedabadi","doi":"10.22038/ijbms.2025.89790.19367","DOIUrl":"10.22038/ijbms.2025.89790.19367","url":null,"abstract":"<p><strong>Objectives: </strong>Brain ischemia remains a leading cause of death and neurological disability worldwide, with current treatments limited by narrow therapeutic windows and insufficient neuroprotection. Kojic acid (KA), a natural compound with demonstrated anti-oxidant and anti-inflammatory properties, has not been thoroughly evaluated in cerebral ischemia. Its limited brain bioavailability may have hindered the identification of its potential therapeutic effects. This study aimed to investigate the effects of both KA and its nanostructured lipid carriers (nKA) in a rat bilateral common carotid artery occlusion (BCCAO) model.</p><p><strong>Materials and methods: </strong>Adult male rats were randomly allocated to seven groups: sham, BCCAO, KA (1 and 10 mg/kg), nKA (1 and 10 mg/kg), and vehicle. Following BCCAO surgery, animals received intraperitoneal treatments for seven days. Behavioral assessments included the modified neurological severity score and grid walk test. Brain and serum samples were collected to evaluate histopathology, gene expression, oxidative stress markers, inflammatory cytokines, and pharmacokinetic parameters.</p><p><strong>Results: </strong>Histological analysis indicated reduced neuronal loss in both KA and nKA-treated groups. Notably, only nKA significantly improved behavioral outcomes. Both treatments reduced the pro-apoptotic gene BAX and the pro-inflammatory cytokine TNF-α, while nKA additionally increased Nrf2 and reduced IL-6 expression. Both formulations mitigated oxidative stress by decreasing reactive oxygen species, protein carbonylation, and malondialdehyde levels, while also increasing glutathione concentrations.</p><p><strong>Conclusion: </strong>Nano-kojic acid showed better neurobehavioral improvements, while both forms reduced oxidative stress and inflammation, indicating neuroprotective potential. Further studies are needed to clarify mechanisms and long-term safety.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 1","pages":"43-54"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118974","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":"Artificial intelligence (AI) in academic publishing: Legitimate use, plagiarism detection, and ethical challenges.","authors":"Leila Arabi, Ali Roohbakhsh, Bizhan Malaekeh-Nikouei, Bibi Sedigheh Fazly Bazzaz","doi":"10.22038/ijbms.2026.27130","DOIUrl":"10.22038/ijbms.2026.27130","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to determine the effect of 8-week high-intensity interval training (HIIT) on oxidative stress and apoptosis in the hippocampus of male rats with type 2 diabetes (T2D). The study focused on examining the role of proliferator-activated receptor gamma co-activator 1α (PGC1α)/Kelch-like ECH-associated protein Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.</p><p><strong>Materials and methods: </strong>Twenty-eight 8-week-old Wistar rats were randomly assigned to one of four groups (n=7): control (Con), type 2 diabetes (T2D), exercise (Ex), and exercise + type 2 diabetes (Ex+T2D). The Ex and Ex+T2D groups completed an 8-week exercise program consisting of 80-100% Vmax and 4-10 intervals. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to assess insulin resistance. The levels of Bcl2, BAX, musculoaponeurotic fibrosarcoma (Maf), Nrf2, Keap1, and PGC1α in the hippocampus were assessed using the western blot method. Additionally, the levels of antioxidant enzymes in the hippocampus were measured using ELISA.</p><p><strong>Results: </strong>The findings indicated that the T2D group had lower levels of antioxidant enzymes, Maf, Bcl2, PGC1α, and Nrf2, and higher levels of BAX and Keap1 in the hippocampus. Conversely, the HIIT group exhibited increased levels of antioxidant enzymes, Maf, Bcl2, Nrf2, and PGC1α, along with decreased levels of BAX and Keap1 in the hippocampus.</p><p><strong>Conclusion: </strong>The study demonstrated that 8-week HIIT was effective in reducing hippocampal apoptosis and oxidative stress induced by T2D by activating the PGC1α-Keap1-Nrf2 signaling pathway. The metabolic changes induced by exercise may lead to an increase in PGC1 expression, which is the primary stimulator of the Keap1-Nrf2 signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 1","pages":"1-2"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118862","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":"Enhancing clomipramine antidepressive effect using nanocomplexes via different routes of administration: A comparative study.","authors":"Abeer Salama, Rabab Kamel, Nourina N Ghoneim, Shereen S Elshaer","doi":"10.22038/ijbms.2025.88730.19176","DOIUrl":"10.22038/ijbms.2025.88730.19176","url":null,"abstract":"<p><strong>Objectives: </strong>Enhancing clomipramine anti-depressive effect using a nanoformulation and investigating its effect via different routes of administration (oral and intranasal) in a depression rat model. Polyelectrolytes nanocomplexes (NC) were prepared by an all-aqueous technique and were composed of different ratios of chitosan (CS) and gum arabic (GA).</p><p><strong>Materials and methods: </strong>Ciprofloxacin (CPX) was administered orally to adult male Wistar albino rats at a dose of 50 mg/kg for 14 days to induce depression. Clomipramine HCl solution and the drug-loaded nano complexes (NC) were administrated for 14 days via the oral route (50 mg/kg) and intranasal route (500 µg/kg).</p><p><strong>Results: </strong>All the prepared drug-loaded nano-complexes (NC) were uniformly distributed (PDI ˂0.2), NC1 (composed of CS:GA 1:1) attained the smallest particle size (200.30 ± 26.07nm) and the most sustained release profile (Mean Release Time= 96.02± 8.36 min.) and has a spherical outline as detected by transmission electron microscope. Treatment with clomipramine-loaded NC via oral and intranasal routes elevated swimming time, serotonin (5-HT), excitatory amino acid transporter 2 (EAAT2) and Gamma-aminobutyric acid (GABA) brain contents, decreased brain content of malondialdehyde (MDA) and nitric oxide (NO), and ameliorated nuclear pyknosis and degeneration of neurons compared to CPX and clomipramine solution. Clomipramine-loaded NC via intranasal routes returned the brain content of 5-HT and EAAT 2 to its normal level and has effect superior than oral route.</p><p><strong>Conclusion: </strong>Clomipramine-loaded NC administered via intranasal route showed an enhanced effect and a higher antidepressant activity than the traditional oral route through alleviating CPX neurological toxicity.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 1","pages":"55-64"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12869017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124728","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":"Hesperidin mitigates DEHP-induced nephrotoxicity through anti-oxidant, anti-apoptotic, and anti-inflammatory pathway modulation: Evidence from Nrf2/HO-1/Keap-1, Bax/Bcl-2/caspase-3, and TLR4/NF-κB axis activation.","authors":"Tuba Karaarslan, Betul Apaydin Yildirim, Fatih Yildirim, Omercan Alat","doi":"10.22038/ijbms.2026.89049.19222","DOIUrl":"https://doi.org/10.22038/ijbms.2026.89049.19222","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to assess the protective role of hesperidin (HSP), a citrus flavonoid, against di-(2-ethylhexyl) phthalate (DEHP)-induced kidney toxicity in rats, focusing on oxidative stress, apoptosis, inflammation, and anti-oxidant defense pathways.</p><p><strong>Materials and methods: </strong>Thirty-five male rats were randomly assigned into five groups (7 per group): control group, DEHP-treated group (1 g/kg), DEHP + HSP (100 mg/kg) group, DEHP + HSP (200 mg/kg) group, and HSP-alone group, and treated orally for 10 consecutive days. Kidney tissues were collected for biochemical assays, including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Gene expression of Nrf2, Keap1, HO-1, Bax, Bcl-2, Caspase-3, TLR-4, and NF-κB was analyzed using real-time PCR, and protein levels were evaluated using Western blotting.</p><p><strong>Results: </strong>DEHP significantly increased oxidative damage and the expression of inflammatory and apoptotic markers, while decreasing anti-oxidant parameters. Co-treatment with HSP, particularly at 200 mg/kg, restored anti-oxidant balance, reduced lipid peroxidation, and down-regulated the expression of TLR-4, NF-κB, and Caspase-3. Moreover, HSP increased Bcl-2 levels and enhanced Nrf2/HO-1 signaling, as confirmed by both gene and protein expression data.</p><p><strong>Conclusion: </strong>HSP demonstrates dose-dependent renoprotective effects against DEHP-induced nephrotoxicity in rats. The protective mechanism involves anti-oxidant enhancement and inhibition of oxidative stress-induced inflammation and apoptosis, supporting the therapeutic potential of HSP in managing phthalate-related renal injury.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 6","pages":"942-951"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793146","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":"Emerging trends in nanomedicine: The role of RNAi-based therapies and onpattro's clinical journey.","authors":"Dilpreet Singh, Satvir Singh, Nitin Tandon, Akshay Thakur, Neena Bedi","doi":"10.22038/ijbms.2026.89795.19366","DOIUrl":"https://doi.org/10.22038/ijbms.2026.89795.19366","url":null,"abstract":"<p><p>Nanomedicine has transformed therapeutic strategies by enabling precise delivery of nucleic acid-based drugs, including small interfering RNA (siRNA), messenger RNA (mRNA), and antisense oligonucleotides. A landmark achievement is Onpattro (patisiran), the first FDA-approved RNAi therapy, which employs lipid nanoparticles (LNPs) to silence transthyretin in hereditary amyloidosis. Its approval validates RNAi as a viable therapeutic modality and underscores the central role of nanocarriers in clinical translation. Despite this success, barriers such as nanoparticle stability, targeted delivery, immunogenicity, and manufacturing scalability remain. Recent advances in mRNA vaccines, CRISPR-based gene editing, and stimuli-responsive nanoparticles are addressing these challenges, supported by growing clinical case studies and real-world data. This review highlights Onpattro's clinical development, compares delivery platforms, discusses translational challenges, and examines emerging technologies that will guide the next generation of RNAi nanomedicines in personalized therapy.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 6","pages":"812-822"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793195","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":"Intranasal administration of spike-specific mRNA-LNP confers more protection than the intramuscular route against SARS-CoV-2.","authors":"Mohsen Abdoli, Hoorieh Soleimanjahi, Sara Soudi, Asghar Abdoli","doi":"10.22038/ijbms.2026.94328.20333","DOIUrl":"10.22038/ijbms.2026.94328.20333","url":null,"abstract":"<p><strong>Objectives: </strong>Intranasal vaccination mimics natural infection and induces mucosal immunity against respiratory viruses. This study compared the immunogenicity and protective efficacy of a nucleoside-modified messenger RNA (mRNA) encoding the SARS-CoV-2 spike protein, encapsulated in lipid nanoparticles (LNPs), administered via intranasal (I.N) versus intramuscular (I.M) routes.</p><p><strong>Materials and methods: </strong>BALB/c mice received mRNA-LNP vaccines at 1, 5, or 10 µg doses intramuscularly. Antibody responses (Immunoglobulin G/IgA [IgG/IgA]), neutralization titers (conventional virus neutralization test [cVNT]), and interferon-gamma (IFN-γ) responses were assessed to select the optimal dose. The selected 5 µg dose was then administered to mice and Syrian hamsters via I.N or I.M routes. Post-challenge, lung viral loads (50% Tissue Culture Infectious Dose [TCID₅₀]/ml) and weight changes were evaluated.</p><p><strong>Results: </strong>The 5 µg dose induced robust humoral and cellular immunity (cVNT >5 log₂). Intranasal delivery elicited strong spike-specific IgA in nasal washes. Although I.M vaccination produced higher serum neutralizing titers (51.2 vs. 22.0), I.N vaccination conferred superior protection with a 4-log reduction in lung viral load (~10¹ TCID₅₀/ml) versus I.M and controls (~10² TCID₅₀/ml). I.N-vaccinated hamsters were completely protected from weight loss, whereas I.M-vaccinated animals showed mild weight reduction (~1%).</p><p><strong>Conclusion: </strong>Intranasal mRNA-LNP administration elicits potent mucosal and systemic immunity and provides superior protection against SARS-CoV-2 challenge compared to I.M vaccination, underscoring its promise as a transformative strategy for respiratory virus vaccines.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"29 9","pages":"1413-1423"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900518","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}