Iranian Journal of Pharmaceutical Research最新文献

{"title":"Preparation and Evaluation of Zn₂(BDC)₂(DABCO)-β-CD MOF as a Dual-Drug Delivery Nanocomposite Containing Tetracycline and Indomethacin for Skin Wound Healing in BALB/c Mice.","authors":"Farya Mirzaei, Negar Motakef Kazemi, Naser Mohamadpour Dounighi, Mostafa Saffari, Sepideh Arbabi Bidgoli","doi":"10.5812/ijpr-167924","DOIUrl":"10.5812/ijpr-167924","url":null,"abstract":"<p><strong>Background: </strong>Skin wounds complicated by infection and inflammation represent a major clinical challenge and require effective delivery systems that combine antimicrobial and anti-inflammatory agents to promote healing. Nanobased systems, such as metal-organic frameworks (MOFs), are promising platforms for dual-drug delivery because of their high porosity, tunable structure, and biocompatibility.</p><p><strong>Objectives: </strong>This study aimed to synthesize a Zn₂(BDC)₂(DABCO)-β-cyclodextrin MOF nanocomposite using a hydrothermal method and to load indomethacin and tetracycline to develop a dual-drug delivery system that enhances the efficiency and therapeutic efficacy of topical treatment for skin wound healing.</p><p><strong>Methods: </strong>The morphology of the nanocomposite was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Zeta potential was measured using a Zetasizer; the crystalline structure was evaluated by X-ray diffraction (XRD); the physicochemical structure was assessed by Fourier transform infrared (FTIR) spectroscopy; and structural porosity before and after drug loading was analyzed by Brunauer-Emmett-Teller (BET) analysis. The system was then evaluated for in vitro cytotoxicity using the MTT assay, cytokine levels in blood samples from treated mice, and in vivo efficacy in mice, compared with the corresponding pure drugs.</p><p><strong>Results: </strong>The synthesized MOF exhibited high crystallinity. The average particle size was 277 nm for the blank nanocomposite and 545 nm for the drug-loaded nanocomposite, with a zeta potential of -2.6 mV. The drug-loading efficiency in phosphate-buffered saline (PBS; pH 7.4) was 28%, with biphasic release comprising an initial burst followed by sustained release over 144 hours. The BET surface area decreased after drug loading. In vitro studies showed that the drug-loaded nanocomposite was noncytotoxic to L929 fibroblast cells at all tested concentrations. The loaded MOF nanocomposite group showed significantly accelerated wound closure (97.5% on day 6) compared with all other groups (P < 0.05). Cytokine assays in mouse blood samples showed increased interleukin 10 (IL-10) and decreased interferon gamma (IFN-γ) in the group treated with the loaded nanocomposite compared with the control group.</p><p><strong>Conclusions: </strong>The Zn₂(BDC)₂(DABCO)-β-CD nanocomposite containing tetracycline and indomethacin exhibited noncytotoxic behavior, enhanced wound-healing efficacy, and sustained drug release under physiological conditions. These findings highlight its potential as a promising topical drug delivery system.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e167924"},"PeriodicalIF":1.7,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549058","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 Effects of Ethyl Acetate Extract of <i>Lygodium microphyllum</i> Leaves.","authors":"Hadi Kuncoro, Erna Muliana, Putri Anggreini, Angga Cipta Narsa, Zulhaerana Bahar, Vina Maulidya, Nurul Annisa","doi":"10.5812/ijpr-171722","DOIUrl":"10.5812/ijpr-171722","url":null,"abstract":"<p><strong>Background: </strong><i>Lygodium microphyllum</i> is traditionally used in Chinese medicine as a decoction to treat hepatitis.</p><p><strong>Objectives: </strong>This study evaluated the in vivo hepatoprotective efficacy and optimal dose of the ethyl acetate extract of <i>L. microphyllum</i> leaves (EALM) against paracetamol-induced liver injury.</p><p><strong>Methods: </strong>A pilot experiment was conducted in 24 male Wistar rats divided into six groups: a normal control group, a paracetamol control group (3 g/kg body weight [BW]), and three EALM groups (200, 400, and 600 mg/kg BW). EALM was administered orally for 14 days, and paracetamol was administered once on day 8. The evaluated parameters included body weight, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and liver histopathology. Paracetamol intoxication caused significant weight loss and increased AST and ALT levels (P < 0.0001).</p><p><strong>Results: </strong>All EALM doses significantly attenuated paracetamol-induced enzyme elevations. Histopathological analysis revealed severe injury, including pyknosis, in the paracetamol group, whereas EALM-treated livers maintained near-normal morphology. Among the tested doses, 200 mg/kg BW showed the most pronounced protective effect.</p><p><strong>Conclusions: </strong>These findings indicate that EALM has significant hepatoprotective activity against paracetamol-induced hepatotoxicity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171722"},"PeriodicalIF":1.7,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549041","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":"CRISPR/Cas9-Engineered HEK293T Cellular Model Harboring the Pathogenic CDKL5 c.172A>T Variant Recapitulates Core Molecular Phenotypes of CDKL5 Deficiency Disorder.","authors":"Fatemeh Faghihi, Jafar Amani, Milad Gholami, Iman Salahshourifar","doi":"10.5812/ijpr-172311","DOIUrl":"10.5812/ijpr-172311","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the CDKL5 gene are strongly associated with severe neurodevelopmental disorders, including atypical Rett syndrome and autism spectrum disorder (ASD).</p><p><strong>Objectives: </strong>This study aimed to establish a cell model carrying a targeted CDKL5 mutation using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and to evaluate the phenotypic and molecular consequences.</p><p><strong>Methods: </strong>A single-guide RNA (sgRNA) targeting exon 2 of CDKL5 was designed using in silico tools to minimize off-target activity. The sgRNA and Cas9 nuclease were cloned into the pSpCas9(BB)-2A-green fluorescent protein (GFP) (PX458) vector and transfected into human embryonic kidney 293T (HEK293T) cells. Following fluorescence-activated cell sorting (FACS), genome-editing efficiency was quantified using a T7 endonuclease I (T7E1) assay and Sanger sequencing. Homology-directed repair (HDR) mediated by single-stranded oligodeoxynucleotide (ssODN) templates was used to introduce a specific missense mutation (c.172A>T; p.Lys58Met). Edited clones were evaluated for CDKL5 expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and cell survival and apoptosis were assessed using Annexin V/propidium iodide (PI) staining and caspase-3 activity assays.</p><p><strong>Results: </strong>The CRISPR/Cas9 construct achieved a mean on-target editing efficiency of 41.6 ± 3.2%, as determined by T7E1 digestion, and sequencing confirmed a heterozygous insertion in 28% of sorted clones. HDR-mediated precise editing was detected in 12% of clones. RT-qPCR analysis showed a 55% reduction in CDKL5 mRNA levels (P < 0.01) in edited cells, whereas Western blotting demonstrated a corresponding 48% decrease in protein expression. Functionally, mutant cells exhibited 25% lower viability (P < 0.05) and 2.3-fold higher apoptosis rates (P < 0.01) than wild-type controls. No significant off-target mutations were detected at the top five predicted loci.</p><p><strong>Conclusions: </strong>We successfully generated a human cell line model of CDKL5-related ASD using CRISPR/Cas9 technology. The mutation induced marked reductions in CDKL5 expression and cell survival. Although this HEK293T-based model provides a useful platform for mechanistic and screening studies, its non-neuronal origin limits its ability to fully recapitulate the neuronal context of CDKL5 deficiency disorder (CDD). This study establishes a novel, precisely engineered human cellular model using advanced CRISPR/Cas9 technology to mechanistically dissect the consequences of CDKL5 deficiency. By introducing a defined missense mutation (c.172A>T; p.Lys58Met) into HEK293T cells, this study provides a robust platform for investigating the role of CDKL5 in neurodevelopmental disorders and supports future therapeutic development.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e172311"},"PeriodicalIF":1.7,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561939","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":"Comparison of Naringenin and Alendronate in the Attenuation of Ovariectomy-Induced Osteoporosis by Modulating Autophagy, Apoptosis, and Oxidative Stress in Rats.","authors":"Hongwei Gao, Pengcheng Ma, Huizhi Chen, Zhengkai Zhang, Nara Davtyan, Jiachun Zheng","doi":"10.5812/ijpr-171182","DOIUrl":"10.5812/ijpr-171182","url":null,"abstract":"<p><strong>Background: </strong>Estrogen deficiency after menopause is a major driver of osteoporosis and has been increasingly linked to dysregulated cellular stress responses, including autophagy and apoptosis, that affect bone remodeling and microarchitecture.</p><p><strong>Objectives: </strong>This study aimed to evaluate the therapeutic effects of naringenin (NA) and alendronate (AL) on ovariectomy (OVX)-induced osteoporosis in rats, with emphasis on autophagy- and apoptosis-related molecular signatures.</p><p><strong>Methods: </strong>Female Sprague-Dawley rats were assigned to sham-operated (SH), OVX, OVX+NA (50 mg/kg/day), or OVX+AL (5 µg/kg/day) groups (n = 10/group) and were treated by oral gavage for 10 weeks. Bone health markers, including bone cell numbers and trabecular weight and volume, were assessed using stereology. Serum estradiol and osteocalcin levels were assayed by enzyme-linked immunosorbent assay. Oxidative markers, including catalase (CAT) and glutathione reductase (GR) activities, were measured using spectrophotometric assays. Femoral mRNA expression of microtubule-associated protein 1 light chain 3 (LC3), beclin 1 (BECN1), autophagy-related 5 (ATG5), caspase 9 (CASP9), and B-cell lymphoma 2 (BCL2) was quantified by reverse transcription quantitative polymerase chain reaction.</p><p><strong>Results: </strong>Ovariectomy reduced estradiol levels compared with SH, and estradiol was not restored by NA or AL. Both treatments mitigated OVX-associated changes in osteocalcin and improved femoral stereological/histomorphometric outcomes, with AL exerting a greater effect across multiple structural and molecular outcomes. NA, but not AL, significantly increased CAT and GR activities relative to OVX. Ovariectomy increased CASP9 and autophagy markers and decreased BCL2; both treatments shifted these transcripts toward SH values, with a stronger effect for AL.</p><p><strong>Conclusions: </strong>Naringenin and AL mitigated OVX-associated osteoporotic changes without restoring systemic estradiol levels, and these effects were accompanied by shifts in apoptosis- and autophagy-related gene expression. These findings suggest that the beneficial effects of AL and NA may be associated with the modulation of oxidative stress and apoptosis- and autophagy-related mechanisms.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171182"},"PeriodicalIF":1.7,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912037","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":"Novel Ethyl 2-Aminopyrano[3,2-c]isochromene-3-carboxylate Derivatives: Synthesis, Spectral Characterization, and Cytotoxicity.","authors":"Mehdi Abaszadeh, Fatemeh Haghani, Ehsan Faghihmirzaei, Salehe Sabouri","doi":"10.5812/ijpr-168116","DOIUrl":"10.5812/ijpr-168116","url":null,"abstract":"<p><strong>Background: </strong>Cancer remains one of the most challenging threats to human health and has prompted intensive research in anticancer drug discovery and synthesis. Isocoumarins are natural lactones with several pharmacological activities, including cytotoxic and anticancer effects.</p><p><strong>Objectives: </strong>This study aimed to synthesize novel ethyl 2-aminopyrano[3,2-c]isochromene-3-carboxylate derivatives and evaluate their cytotoxicity against the MCF-7 breast cancer and A549 lung cancer cell lines, in comparison with a normal cell line (MCF-10A human breast cells).</p><p><strong>Methods: </strong>First, 4-hydroxyisocoumarin was prepared. A series of ethyl 2-aminopyrano[3,2-c]isochromene-3-carboxylate derivatives was then synthesized via a one-pot, three-component reaction of 4-hydroxyisocoumarin, ethyl cyanoacetate, and aromatic aldehydes in ethanol under reflux in the presence of triethylamine. The resulting compounds were characterized using standard spectroscopic techniques, including IR, ¹H NMR, and ¹³C NMR, as well as elemental analyses. Finally, the cytotoxicity of the synthesized compounds was evaluated in MCF-7, A549, and MCF-10A cell lines using a colorimetric MTT assay.</p><p><strong>Results: </strong>The compounds were successfully synthesized, and the cytotoxicity assay demonstrated dose-dependent cytotoxic effects in the tested cell lines. Most compounds exhibited moderate or low toxicity, whereas some were non-toxic in these cells. The most cytotoxic compounds were 4g, 4n, and 4m, with IC₅₀ values of 120.77 ± 7.64, 141.43 ± 13.81, and 168.62 ± 3.59 μg/mL against MCF-7 cells, respectively, and 4a, with an IC₅₀ value of approximately 131.12 ± 11.00 μg/mL against A549 cells. Compared with MCF-10A non-cancerous cells, these compounds showed selectivity indices (SIs) of 4.14, 1.64, 2.47, and 3.42, respectively.</p><p><strong>Conclusions: </strong>The compounds were synthesized in high yields and exhibited moderate-to-mild toxicity toward MCF-7, A549, and MCF-10A cells. Notably, halogen substitution at the ortho position of the phenyl ring increased toxicity, particularly in the MCF-7 cell line. However, the lack of selectivity observed for most compounds indicates that further structural refinement is required before this scaffold can be considered a viable anticancer lead.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168116"},"PeriodicalIF":1.7,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561937","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 a Saffron-Based (<i>Crocus sativus</i> L.) Herbal Supplement on Sleep Disturbances in Pulmonary Sarcoidosis: A Randomized Single-Blind Controlled Trial.","authors":"Zahra Moghimi Dehkordi, Jamshid Salamzadeh, Maria Tavakoli-Ardakani, Atefeh Abedini, Farzaneh Dastan","doi":"10.5812/ijpr-169041","DOIUrl":"10.5812/ijpr-169041","url":null,"abstract":"<p><strong>Background: </strong>Sleep disturbances in pulmonary sarcoidosis increase fatigue and reduce quality of life; however, standard anti-inflammatory treatments provide limited benefit. Saffron (<i>Crocus sativus</i> L., family Iridaceae), which has anti-inflammatory and neuromodulatory properties, may improve sleep, although its effects in this population have not been studied.</p><p><strong>Objectives: </strong>This study evaluated whether 60 days of saffron supplementation (30 mg twice daily) improves sleep quality, reduces daytime sleepiness and fatigue, and enhances quality of life in patients with pulmonary sarcoidosis.</p><p><strong>Methods: </strong>In this single-blind randomized controlled trial, 76 adults with pulmonary sarcoidosis, confirmed according to the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders criteria, and Pittsburgh Sleep Quality Index (PSQI) scores ≥ 5 were assigned to groups using permuted block randomization (block size, 4). Allocation concealment was ensured using opaque, sealed, sequentially numbered envelopes. Participants were randomly allocated to receive either saffron (30 mg twice daily) plus sleep-hygiene counseling or counseling alone for 60 days. Sleep quality, daytime sleepiness, fatigue, and quality of life were assessed at baseline and day 60 using the PSQI, General Sleep Disturbance Scale (GSDS), Epworth Sleepiness Scale (ESS), Fatigue Assessment Scale (FAS), Patient-Reported Outcomes Measurement Information System (PROMIS)-fatigue, and 12-item Short Form Health Survey (SF-12).</p><p><strong>Results: </strong>Of the 76 participants enrolled, 72 completed the study (36 per group). Compared with the control group, saffron supplementation significantly improved PSQI (adjusted mean difference [MD], -2.21), GSDS (adjusted MD, -14.60), ESS (adjusted MD, -2.46), FAS (adjusted MD, -4.58), and the PROMIS global physical health score (adjusted MD, 1.65) (all P < 0.001). Significant improvements were also observed in the SF-12 physical (P = 0.03) and mental (P = 0.003) component scores. No serious adverse events occurred.</p><p><strong>Conclusions: </strong>Adjunctive saffron supplementation significantly improved sleep quality, reduced daytime sleepiness and fatigue, and enhanced quality of life in patients with pulmonary sarcoidosis. Larger, placebo-controlled studies are warranted to confirm these findings.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169041"},"PeriodicalIF":1.7,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549079","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":"Pharmacologic Sedation-Related Respiratory Complications in Pediatric Dentistry: A Decade-Long Scoping Review.","authors":"Leila Mohammadpour-Belvirdy, Elham Sadati, Maryam Hassanzad, Ali Valinejadi","doi":"10.5812/ijpr-170313","DOIUrl":"10.5812/ijpr-170313","url":null,"abstract":"<p><strong>Context: </strong>Procedural sedation is widely used in pediatric dentistry to facilitate dental care in uncooperative children. From a pharmacological perspective, sedative agents differ substantially in their mechanisms of action, routes of administration, and safety profiles. Among the reported adverse effects, respiratory complications remain the most clinically significant and potentially life-threatening. Despite extensive clinical use, a comprehensive synthesis of respiratory adverse events (RAEs) associated with commonly used sedative drugs in pediatric dental settings is lacking. This scoping review aimed to map the existing evidence on respiratory complications associated with pharmacological sedation in pediatric dentistry.</p><p><strong>Evidence acquisition: </strong>A scoping review was conducted in accordance with established methodological frameworks. Electronic databases were systematically searched for studies reporting the use of sedative or anesthetic agents in pediatric dental procedures. Eligible studies included clinical trials, cohort studies, case series, and retrospective analyses that documented respiratory outcomes. Data were extracted on patient characteristics, sedative agents and combinations, dosages, routes of administration, monitoring methods, and reported respiratory complications.</p><p><strong>Results: </strong>The included studies showed substantial variability in sedation protocols. The most frequently reported agents were benzodiazepines, chloral hydrate, ketamine, propofol, dexmedetomidine, and opioid combinations. For clarity, respiratory complications in this review are categorized as mild (e.g., transient oxygen desaturation, partial airway obstruction), moderate (e.g., hypoventilation requiring intervention), and severe (e.g., laryngospasm, apnea requiring advanced airway management). RAEs ranged from mild, transient events (e.g., oxygen desaturation and airway obstruction) to more serious conditions, including laryngospasm and apnea. Most complications were managed successfully with basic airway maneuvers, supplemental oxygen, or brief positive-pressure ventilation. Severe outcomes requiring advanced airway intervention were rare. Continuous respiratory monitoring, particularly pulse oximetry and capnography to facilitate earlier detection of ventilatory compromise, was consistently associated with prompt management of adverse events.</p><p><strong>Conclusions: </strong>Pharmacological sedation in pediatric dentistry is generally safe when appropriate drug selection, dosing, and monitoring are used. Respiratory complications are relatively common but are typically mild and reversible. From a pharmacological perspective, careful consideration of sedative combinations, cumulative respiratory depressant effects, and vigilant monitoring is essential to optimize patient safety. Further high-quality studies are needed to refine evidence-based sedation protocols and minimize respiratory risks.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170313"},"PeriodicalIF":1.7,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549013","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":"RNA-Seq Analysis of Morphine-Induced Gene Expression Changes in the Mouse Nucleus Accumbens.","authors":"Seyed Mahmoud Pourmand, Shahrzad Nazari, Elham Nazari, Reza Arezoomandan, Gholamreza Hassanzadeh, Sahar Eshrati, Morteza Karami-Zarandi, Mohammad Bagher Saberi-Zafarghandi","doi":"10.5812/ijpr-169453","DOIUrl":"10.5812/ijpr-169453","url":null,"abstract":"<p><strong>Background: </strong>Opioid use disorder (OUD) remains a critical global health challenge. The nucleus accumbens (NAc), a key region of the brain reward system, plays an essential role in opioid-induced neuroadaptations. Characterizing gene expression alterations in reward-system regions, such as the NAc, is essential for elucidating the molecular mechanisms underlying addiction. In recent years, bioinformatics has emerged as a rapidly advancing field and has played a pivotal role in elucidating molecular mechanisms and in advancing computational biology.</p><p><strong>Objectives: </strong>This study aimed to characterize transcriptomic changes in the NAc of mice following chronic morphine administration using RNA sequencing and bioinformatic analysis.</p><p><strong>Methods: </strong>RNA sequencing (RNA-Seq) data from morphine- and saline-treated mice were obtained from the Gene Expression Omnibus database via the Sequence Read Archive. Following quality control and alignment, differentially expressed genes (DEGs) were identified using the DESeq2 package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, as well as protein-protein interaction (PPI) network analyses, were performed to evaluate the functional implications of these genes.</p><p><strong>Results: </strong>Principal component analysis (PCA) revealed distinct transcriptomic profiles between the morphine and control groups. A total of 143 DEGs were identified, including 125 up-regulated and 18 down-regulated genes. Enrichment analyses indicated significant involvement in synaptic signaling, ion transport, and neurodegenerative pathways. Protein-protein interaction (PPI) network analysis identified several hub genes, including fgf3 (fibroblast growth factor 3), mki67 (marker of proliferation Ki-67), grin2a/grin2b (glutamate receptor NMDA subunits 2A/2B), gli1 (GLI family zinc finger 1), and ago2 (argonaute RISC catalytic component 2), which are associated with synaptic plasticity, neurogenesis, and epigenetic regulation.</p><p><strong>Conclusions: </strong>Chronic morphine exposure induces widespread gene expression changes in the NAc, engaging pathways associated with synaptic remodeling, neuronal excitability, and addiction-related neuroplasticity. These findings provide a molecular framework for understanding opioid-induced adaptations and identify candidate targets, including N-methyl-D-aspartate (NMDA) receptor subunits, fgf3, and ago2, for potential therapeutic intervention. Future studies should functionally validate these targets and evaluate their translational relevance in the context of OUD.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169453"},"PeriodicalIF":1.7,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549077","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":"Berberine Alleviates Hepatic Steatosis by Restoring CPT1α Histone Acetylation and Modulating HDAC2/SIRT2.","authors":"Chenye Shi, Shuai Ma, Hua Bian, Qiong Liu, Huandong Lin, Xin Gao, Haifu Wu, Hongmei Yan, Xinxia Chang","doi":"10.5812/ijpr-170783","DOIUrl":"10.5812/ijpr-170783","url":null,"abstract":"<p><strong>Background: </strong>High-fat diet (HFD)-driven hepatic steatosis is associated with impaired mitochondrial fatty acid oxidation and dysregulated expression of genes that control lipid disposal. Carnitine palmitoyltransferase 1α (CPT1α), encoded by Cpt1a, is the rate-limiting enzyme for mitochondrial fatty acid β-oxidation and responds to nutritional stress. However, the chromatin mechanisms that regulate Cpt1a in diet-induced steatosis remain incompletely defined.</p><p><strong>Objectives: </strong>To map histone modifications at the hepatic Cpt1a locus and determine whether berberine (BBR) is associated with the restoration of Cpt1a transcription through histone acetylation remodeling.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were assigned to the normal diet (ND), high-fat diet (HFD), or berberine (BBR)+HFD group (n = 8 initially), with individual rats as the experimental unit. ChIP-qPCR was performed on archived liver samples (ND, n = 6; HFD, n = 8; BBR+HFD, n = 8) and normalized to input DNA. In BRL cells, TSA (100 nM) and SAHA (20 μM) were used to assess HDAC-sensitive regulation of Cpt1a.</p><p><strong>Results: </strong>HFD reduced H3/H4 acetylation and increased H3K9 methylation at Cpt1a regulatory regions. BBR restored H3/H4 acetylation, selectively reduced H3K9me3 at +12 kb, and attenuated HFD-induced increases in HDAC2 and SIRT2 mRNA (approximately 40-fold and 3.8-fold, respectively) toward baseline. TSA and SAHA increased Cpt1a mRNA at 24 h by approximately 8.1-fold and 5.4-fold, respectively. Palmitate reduced Cpt1a expression by approximately 58%, and this repression was reversed by BBR or TSA.</p><p><strong>Conclusions: </strong>BBR alleviates HFD-induced hepatic steatosis, concomitant with the restoration of Cpt1a histone acetylation and modulation of HDAC2/SIRT2. These data support, but do not prove, an HDAC2/SIRT2-linked chromatin mechanism and should be interpreted as a candidate pathway requiring further functional validation.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170783"},"PeriodicalIF":1.7,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549050","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":"miR-146a-Enriched Mesenchymal Stem Cell-Derived Extracellular Vesicles Prolong Corneal Allograft Survival by Modulating Local and Systemic Immune Responses.","authors":"Xuting He","doi":"10.5812/ijpr-171093","DOIUrl":"10.5812/ijpr-171093","url":null,"abstract":"<p><strong>Background: </strong>Corneal allograft rejection remains a leading cause of graft failure. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may provide new options for modulating the immune response to allografts.</p><p><strong>Objectives: </strong>This study aimed to determine whether miR-146a-enriched EVs could prolong corneal allograft survival by modulating local and systemic immune responses.</p><p><strong>Methods: </strong>After corneal allografting from C57BL/6 to BALB/c mice, recipients received subconjunctival injections of PBS, miR-NC-EVs, or miR-146a-EVs isolated from human umbilical cord mesenchymal stem cells (hUCSCs). Local inflammatory and regulatory factors in ocular tissues were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) to quantify the expression of interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), tumor necrosis factor (TNF)-α, and forkhead box protein 3 (Foxp3). Systemic cytokine profiles were assessed in recipient sera using enzyme-linked immunosorbent assay (ELISA) to measure interferon (IFN)-γ, interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-β.</p><p><strong>Results: </strong>Clinical rejection scores were markedly reduced, with significant improvements in opacity, edema, and neovascularization. RT-PCR analysis of corneal tissue showed miR-146a overexpression, downregulation of IRAK1 and TRAF6, a significant reduction in TNF-α mRNA, and increased Foxp3 expression. ELISA analysis of systemic IFN-γ and IL-17 showed that treatment with miR-146a-EVs resulted in lower systemic IFN-γ and IL-17 levels and significantly higher levels of the anti-inflammatory cytokines, IL-10 and TGF-β.</p><p><strong>Conclusions: </strong>This study identifies miR-146a-EVs as a novel cell-free therapy that effectively prolongs corneal transplant survival. The treatment exerts dual immunomodulatory effects by regulating local inflammatory pathways and shifting systemic cytokine profiles toward an anti-inflammatory state, thereby offering a targeted strategy to prevent transplant rejection.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171093"},"PeriodicalIF":1.7,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591813","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}