Iranian Journal of Pharmaceutical Research最新文献

{"title":"Evaluation of Antimicrobial Activity of Novel Chimeric M-PEX12 Peptide Against <i>Acinetobacter baumannii</i>.","authors":"Yasin Rakhshani, Hamideh Mahmoodzadeh Hosseini, Seyed Ali Mirhosseini, Fatah Sotoodehnejadnematalahi, Jafar Amani","doi":"10.5812/ijpr-154484","DOIUrl":"10.5812/ijpr-154484","url":null,"abstract":"<p><strong>Background: </strong><i>Acinetobacter baumannii</i>-induced nosocomial pneumonia and its associated biofilm infections pose significant clinical challenges due to high rates of antibiotic resistance. Traditional antibiotic treatments encounter numerous obstacles, making antimicrobial peptides (AMPs) a promising alternative for controlling such pathogens. The emergence of multidrug-resistant strains necessitates the exploration of innovative therapeutic strategies.</p><p><strong>Objectives: </strong>We recently designed a novel hybrid peptide, M-PEX12, which exhibits antimicrobial activity and low toxicity in vitro. To confirm its therapeutic potential, we evaluated it in both in vitro and in vivo settings.</p><p><strong>Methods: </strong>M-PEX12 was evaluated using time-kill kinetics, thermal stability, reactive oxygen species (ROS) generation, biofilm inhibition assays, scanning electron microscopy (SEM), cytotoxicity tests, and virulence gene expression analysis. Its in vivo activity against <i>A. baumannii</i> was also assessed in an animal model.</p><p><strong>Results: </strong>The time-kill kinetics assay indicated that exposure to M-PEX12 at 1x minimum inhibitory concentration (MIC) (33/154) and 2x MIC resulted in over 95% reduction in bacterial populations within 30 minutes. Notably, the bacteria did not develop resistance to increased temperatures. M-PEX12 effectively disrupted biofilm formation at various concentrations. Field emission SEM revealed significant ultrastructural deformities in <i>A. baumannii</i> cell walls. Treatment with M-PEX12 increased production of intracellular ROS and decreased cell viability in a concentration-dependent manner. Cytotoxicity assays showed no significant effect on <i>HEK293</i> cell viability. Additionally, expression levels of <i>omp33</i>, <i>csuE</i>, <i>bfmR</i>, and <i>ompA</i> were significantly reduced. The antimicrobial efficacy of M-PEX12 was confirmed in vivo.</p><p><strong>Conclusions: </strong>M-PEX12 exhibited significant antimicrobial activity and low toxicity in a mouse model, suggesting its potential as a treatment for drug-resistant bacterial infections.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e154484"},"PeriodicalIF":1.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730964","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":"Investigation of the Antioxidant and Cellular Toxicity Activities of Gold Nanoparticles Synthesized Using <i>Cichorium intybus</i> Extract on a Liver Cancer Cell Line.","authors":"Mohammad Mohammad-Alizadeh, Ahmad Asgharzadeh, Maryam Tatari","doi":"10.5812/ijpr-159348","DOIUrl":"10.5812/ijpr-159348","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer is increasing in different parts of the world and is the fourth leading cause of cancer death globally.</p><p><strong>Objectives: </strong>The present study aims to synthesize and analyze the characterization of gold nanoparticles (AuNPs) synthesized by <i>Cichorium intybus</i> extract and evaluate their antioxidant and cellular toxicity activity against liver cancer cells (HepG2).</p><p><strong>Methods: </strong>The synthesized AuNPs were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and fourier-transform infrared spectroscopy (FTIR). The antioxidant activity of the nanoparticles was assessed using the DPPH test, and their cytotoxicity activity was analyzed using the MTT method.</p><p><strong>Results: </strong>The results indicate that the AuNPs are crystalline materials with a particle size of less than 100 nm, with a mean particle size of 23.94 nm. The FTIR study reveals the presence of biochemical groups that act as reducing factors. The results demonstrate that antioxidant activity increases with concentration, with 87% inhibition of DPPH free radical scavenging observed at 250 µg/mL. Cell toxicity results in liver cancer cell lines (HepG2) demonstrated significant cytotoxicity in a time- and dose-dependent manner. The percentage of cell viability at a concentration of 1000 µg/ml after 24, 48, and 72 hours was determined to be 45%, 51%, and 22%, respectively.</p><p><strong>Conclusions: </strong>The present study revealed the simple cost-effective and environmentally friendly method that could be employed from food to pharmaceutical industries.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e159348"},"PeriodicalIF":1.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730968","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":"Study on the Role of Schisandrin B in Ameliorating Hepatic Ischemia-Reperfusion Injury by Modulating Hepatocyte Autophagy.","authors":"Zhao Fei, Pan Haihang, Chen Xueyang, Shen Miao","doi":"10.5812/ijpr-157033","DOIUrl":"10.5812/ijpr-157033","url":null,"abstract":"<p><strong>Background: </strong>Hepatic ischemia-reperfusion injury (HIRI) significantly affects the prognosis of liver surgery, such as hepatocellular carcinoma resection and liver transplantation. However, the pathogenesis of HIRI has not been fully elucidated, and prevention and treatment strategies remain challenging.</p><p><strong>Methods: </strong>A mouse model of HIRI was established, and schisandrin B (Sch B) was used to intervene in HIRI. The effect of Sch B on HIRI was assessed using hematoxylin and eosin (HE) staining, quantitative polymerase chain reaction (qPCR), Western blot (WB), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of the HIRI mouse model was significantly increased, indicating the successful construction of the HIRI mouse model. In the Sch B intervention group, serum ALT and AST levels were significantly decreased. Hematoxylin and eosin staining and qPCR results demonstrated that Sch B could reduce HIRI in mice. The qPCR and immunohistochemistry showed that Sch B reduced HIRI in mice by decreasing the expression of autophagy-related factors Beclin-1 and LC3-II.</p><p><strong>Conclusions: </strong>Additionally, qPCR and immunohistochemical results indicated that Sch B reduced HIRI by decreasing the expression of autophagy-related factors (Beclin-1 and LC3-II) and hepatocyte damage-related factors (caspase-3, caspase-9, and Bax), thereby reducing HIRI in mice. The results of electron microscopy, immunohistochemistry, and qPCR confirmed that Sch B could reduce autophagy and alleviate HIRI.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e157033"},"PeriodicalIF":1.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730989","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":"Pharmacokinetics and Bioequivalence of Two Formulations of Apixaban Tablets: A Double-Blind, Single-Dose, Crossover Study in Healthy Subjects.","authors":"Erfan Abdollahizad, Azadeh Haeri, Abolghasem Jouyban, Mohammad Reza Afshar Mogaddam, Zahra Abbasian, Simin Dadashzadeh","doi":"10.5812/ijpr-157714","DOIUrl":"10.5812/ijpr-157714","url":null,"abstract":"<p><strong>Background: </strong>The present study aimed to determine the pharmacokinetic parameters and bioequivalence of the test medicinal product, apixaban 5 mg tablet, and its reference product, Eliquis^®, in healthy male and female subjects under a fasted state.</p><p><strong>Methods: </strong>Before in vivo evaluation, the quality control parameters of the products were evaluated and compared. This study was a single-dose, double-blind, 2-sequence, crossover, 2-period, randomized bioequivalence and pharmacokinetic study in 24 healthy individuals with a two-week washout period between doses. A series of blood samples were obtained over 48 hours after dose administration, and the samples were analyzed for their apixaban content using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. The pharmacokinetic parameters were computed using non-compartmental analysis.</p><p><strong>Results: </strong>Both products passed the in vitro quality control criteria. Following administration of the apixaban tablet, the area under curve (AUC)_0-t, AUC_0-∞, and maximum plasma concentration (C_max) mean values for the test product were 1284.0 ng.h/mL, 1368.2 ng.h/mL, and 157.4 ng/mL, respectively, and for the reference product were 1310.6 ng.h/mL, 1406.5 ng.h/mL, and 157.6 ng/mL, respectively. The 90% confidence intervals (CI) of the geometric mean ratio for AUC_0-t (91.4 - 105.9), AUC_0-∞ (92.9 - 106.9), and C_max (87.1 - 101.9) fell within the predefined accepted range of 80% - 125%. No serious adverse events were observed.</p><p><strong>Conclusions: </strong>The test product (apixaban 5 mg tablet) and reference product (Eliquis^®) achieved regulatory requirements for bioequivalence in healthy individuals under a fasted state.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e157714"},"PeriodicalIF":1.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730986","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":"Antimicrobial, Anti-inflammatory, Angiogenesis, and Wound Healing Activities of Copper Nanoparticles Green Synthesized by <i>Lupinus arcticus</i> Extract.","authors":"Nizar H Saeedi, Abdullah D Alanazi, Rawaf Alenazy, Abdullah F Shater","doi":"10.5812/ijpr-147434","DOIUrl":"10.5812/ijpr-147434","url":null,"abstract":"<p><strong>Background: </strong>Wound healing and antibiotic resistance of pathogenic microbes have become global issues with serious consequences for the treatment of infectious diseases.</p><p><strong>Objectives: </strong>The present study aimed to evaluate the antibacterial, anti-inflammatory, angiogenic, and wound healing properties of copper nanoparticles (CuNPs) synthesized using <i>Lupinus arcticus</i> extract.</p><p><strong>Methods: </strong>The green synthesis was conducted using the precipitation method. The antibacterial activity of CuNPs against both methicillin-sensitive and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) strains was evaluated. The effects of CuNPs on protein leakage, the expression levels of biofilm-related genes [e.g., intracellular adhesion A (icaA), intracellular adhesion D (icaD), and elastin-binding protein (EbpS) genes] in MRSA, as well as its impact on wound healing, angiogenesis, and anti-inflammatory effects, were assessed.</p><p><strong>Results: </strong>The CuNPs exhibited a spherical shape with dimensions ranging from 10 to 85 nm. Both CuNPs alone and in combination with gentamicin (GNT) inhibited biofilm formation in MRSA, with minimum biofilm inhibitory concentration (MBIC₅₀) values of 6.6 µg/mL and 0.50 µg/mL for MRSA, respectively. The CuNPs significantly (P < 0.05) downregulated the expression levels of icaA, icaD, and EbpS in MRSA, particularly at half the minimum inhibitory concentration (1/2 MIC) and the minimum inhibitory concentration (MIC). Additionally, CuNPs markedly (P < 0.001) increased protein leakage in MRSA. The CuNPs demonstrated potent in vitro wound healing effects, promoting fibroblast cell proliferation and wound closure in a dose-dependent manner. Our results indicated a significant (P < 0.05) increase in the expression of HLA-G5 and VEGF-A genes in cells exposed to CuNPs. Furthermore, CuNPs reduced the expression levels of inflammatory genes in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (P < 0.05).</p><p><strong>Conclusions: </strong>The findings of this experimental test indicate that CuNPs, particularly in conjunction with GNT, exhibits promising antibacterial effects against MRSA without causing cytotoxicity to normal cells. This study also demonstrated that green-synthesized CuNPs possesses significant wound-healing properties through its antibacterial activity, inhibition of biofilm formation, induction of angiogenesis, and reduction of inflammation. However, further experiments are necessary to elucidate the precise mechanisms of action and potential toxicity of CuNPs.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e147434"},"PeriodicalIF":1.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707494","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":"Design, Synthesis, and Evaluation of Cytotoxic Effects of Functional Fatty Acid Derivatives as Potential Antineoplastic Agents for Breast Cancer.","authors":"Maryam Hosseini, Farzad Kobarfard, Salimeh Amidi, Shaya Mokhtari, Anna Sedaghat, Soraya Shahhosseini","doi":"10.5812/ijpr-159523","DOIUrl":"10.5812/ijpr-159523","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is among the most prevalent cancers in women and is the leading cause of mortality among women worldwide. Although a definitive cure for breast cancer remains elusive, essential fatty acids offer a promising therapeutic avenue.</p><p><strong>Objectives: </strong>The present study aimed to synthesize 16 derivatives of docosahexaenoic acid (DHA) and linoleic acid (LA) and evaluate their anti-cancer properties in vitro.</p><p><strong>Methods: </strong>Fourteen derivatives of LA and DHA were synthesized using a coupling method, while two ethylenediamine derivatives were synthesized via an ester intermediate. Molecular modeling was conducted using AutoDock Vina software. The cytotoxic effects of all compounds were assessed using the MTT assay on breast adenocarcinoma (MCF-7) cells. The mechanism of cell death induction by derivatives with the most favorable EC₅₀ values was determined through annexin V-FITC/PI flow cytometry analysis, focusing on early and late apoptosis.</p><p><strong>Results: </strong>Docking results revealed that these compounds effectively interact with residues in the PTPB1 active site. All synthesized DHA and LA derivatives demonstrated cytotoxic effects on the MCF-7 cell line, with no significant cytotoxicity observed in normal human dermal fibroblasts (HDFs). Compounds D3 and L3, with EC₅₀ values of 15.96 ± 2.89 μM and 24.64 ± 1.81 μM, respectively, were identified as the most potent anti-cancer compounds among the derivatives.</p><p><strong>Conclusions: </strong>The findings indicate that these functional fatty acid derivatives significantly reduce cancer cell viability. In addition to necrosis, compounds L3 and D3 induced apoptosis, with apoptosis rates of 20.5% and 47.1%, respectively.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e159523"},"PeriodicalIF":1.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730958","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":"Development of a Potential Bone-Seeking Radiopharmaceutical by Sodium Pyrophosphate Labeled ¹⁸⁸Rhenium (¹⁸⁸Re-PYP) for Bone Pain Palliation.","authors":"Mahmoud Moradi, Mehdi Salehi Barough, Leila Moghaddam-Banaem, Fariba Johari Daha, Sahar Rajabi-Moghadam","doi":"10.5812/ijpr-153691","DOIUrl":"10.5812/ijpr-153691","url":null,"abstract":"<p><strong>Background: </strong>Technetium-^99m (^99mTc)-pyrophosphate (PYP) has been widely utilized in diagnosing bone disorders and certain cardiac conditions, such as amyloidosis, allowing for accurate imaging and detection of abnormalities within heart tissue. Rhenium, being in the same group as technetium in the periodic table, shares similar chemical properties. Rhenium-¹⁸⁸ (¹⁸⁸Re) possesses favorable nuclear properties for theranostic applications.</p><p><strong>Objectives: </strong>This study focused on labeling sodium PYP with ¹⁸⁸Re and its biodistribution.</p><p><strong>Methods: </strong>Different samples with varying amounts of PYP (5 - 22 mg), SnCl₂.2H₂O (0.2 - 6.0 mg), and ascorbic acid (0.3 - 7 mg) were prepared in vials. Initially, 0.08 mg of potassium perrhenate as a carrier in 1 mL saline was added to each vial. Subsequently, 370 - 3700 MBq of ¹⁸⁸ReO₄ ^- was added to the initial solution. The pH of the solutions was varied between 3 and 8. The compound was shaken vigorously for 30 seconds. Product incubation was performed in a secured container for 30 minutes at room temperature.</p><p><strong>Results: </strong>Maximum labeling yield was achieved with 10 mg of PYP, 1 mg of SnCl₂.2H₂O, 0.3 mg of ascorbic acid, and 0.08 mg of potassium perrhenate as a carrier in 1 mL with 370 MBq of ¹⁸⁸ReO₄ ^- at pH 5. This compound showed good stability, and a radiochemical purity of 98.96% ± 0.1% was obtained. The biodistribution results of the radiolabeled ligand revealed that the maximum affinity for ¹⁸⁸Re-PYP was for bone after 4 hours, which was 2.24% ± 0.667% ID/g. The maximum uptake for the kidney, spleen, and liver was 1.53% ± 0.378%, 0.13% ± 0.086%, and 0.18% ± 0.12% ID/g, respectively.</p><p><strong>Conclusions: </strong>The present study investigated the initial labeling efficiency of ¹⁸⁸Re-PYP along with its biodistribution and in vitro stability. The ¹⁸⁸Re-PYP conjugate, prepared under optimized conditions, demonstrated radiochemical purity and stability. The biodistribution of the compound in mice exhibited high affinity for bone, whereas the complex was eliminated through the kidneys.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e153691"},"PeriodicalIF":1.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730960","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":"Ellagitannins (Ellagic Acid, Urolithin A, Urolithin B) Inhibit the Catalytic Activity of Human Recombinant Metalloproteinase 9.","authors":"Nigar Houssein-Zadeh, Leila Sadeghi, Gholamreza Dehghan","doi":"10.5812/ijpr-148332","DOIUrl":"10.5812/ijpr-148332","url":null,"abstract":"<p><strong>Background: </strong>Ellagitannins are well-recognized for their antioxidant, chemopreventive, anti-inflammatory, and neuroprotective efficacy. Due to their poor absorption and extensive catabolism, it is proposed that urolithins, as ellagic acid (EA) metabolites, are the real active molecules exerting these biological functions.</p><p><strong>Objectives: </strong>This research evaluated the inhibitory effects of EA, urolithin A (Uro A), and urolithin B (Uro B) on the activity of recombinant human matrix metalloproteinase 9 (rhMMP-9). Dysregulation of MMP-9 activity is directly involved in various pathologies; therefore, inhibition of this enzyme has clinical importance.</p><p><strong>Methods: </strong>The rhMMP-9 activity was measured by a standard protease assay with casein as the substrate in the presence and absence of natural compounds, and the corresponding kinetic parameters were calculated. Interaction affinity between the enzyme and each of the ellagitannins studied was determined by the surface plasmon resonance (SPR) method. Molecular docking was performed using the C-terminally truncated human pro-MMP-9 structure as the receptor protein (PDB ID 1L6J) to predict ligand-receptor interaction and visualize the in vitro results.</p><p><strong>Results: </strong>The rhMMP-9 assay showed that EA, Uro A, and Uro B demonstrated inhibitory activity with IC₅₀ values of 17.14 µM, 33.29 µM, and 13.17 µM, respectively. Kinetic interaction parameters calculated using SPR analysis showed the lowest KD for Uro B (4.3 × 10^-5 M), compatible with its IC₅₀. KD values calculated were 11.3 × 10^-5 M for EA and 6.7 × 10^-5 M for Uro A. A mixed type of inhibition with a non-competitive-uncompetitive pattern for Uro A and Uro B and a competitive-non-competitive pattern for EA was revealed.</p><p><strong>Conclusions: </strong>Our results showed the promising inhibitory potential of EA, Uro B, and Uro A to affect the catalytic activity of the MMP-9 enzyme and also confirmed the fibronectin domain as a potential site for drug design against MMP-9.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e148332"},"PeriodicalIF":1.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730962","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 Early TLR4 Blockade with Compound C34 in Temporal Lobe Epilepsy: Alleviation of Neuroinflammation and Apoptosis.","authors":"Roya Varmazyar, Nima Naderi, Hanieh Javid, Rasoul Ghasemi, Hamid Gholami Pourbadie","doi":"10.5812/ijpr-159165","DOIUrl":"10.5812/ijpr-159165","url":null,"abstract":"<p><strong>Background: </strong>Temporal lobe epilepsy (TLE) is a chronic neurological disorder characterized by hippocampal necrosis and apoptosis. Neuroinflammation plays a critical role in the pathophysiology of TLE, with toll-like receptor 4 (TLR4) serving as a key mediator. Activation of TLR4 leads to the release of pro-inflammatory cytokines, such as IL-6 and TNF-α, which contribute to neuronal injury and apoptosis. The TLR4 signaling pathway promotes neuroinflammation through nuclear factor kappa-B (NF-κB) activation, further exacerbating neuronal damage over time. Therefore, timely inhibition of TLR4 may help mitigate neuroinflammation and alleviate epilepsy symptoms.</p><p><strong>Objectives: </strong>This study aimed to determine whether early inhibition of TLR4 can regulate seizures and apoptosis by targeting the NF-κB1 signaling pathway.</p><p><strong>Methods: </strong>The TLR4 inhibitor C34 was administered intraventricularly to two experimental groups. The first group received the injection immediately after pilocarpine-induced seizures, while the second group was treated 24 hours post-pilocarpine injection. The expression levels of NF-κB1, TNF-α, and caspase-3 were analyzed using western blotting. Neuronal death in the hippocampus was assessed using hematoxylin and eosin (H&E) staining.</p><p><strong>Results: </strong>The results demonstrated that early inhibition of TLR4 by C34, administered immediately after seizure induction, significantly reduced NF-κB1, TNF-α, and caspase-3 expression levels compared to the group that received C34, 24 hours later. Additionally, early treatment with C34 significantly prevented pilocarpine-induced neuronal death in the hippocampus compared to the late treatment group.</p><p><strong>Conclusions: </strong>These findings highlight the importance of early intervention in reducing neuronal death and suppressing neuroinflammation in an epilepsy model. Inhibiting TLR4 immediately after seizure induction may serve as a potential therapeutic strategy to minimize inflammation-mediated neuronal damage in TLE. Further research is needed to explore the long-term effects of TLR4 inhibition in epilepsy treatment.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e159165"},"PeriodicalIF":1.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730972","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":"KMT2D Induces M1 Macrophage Polarization to Repress Non-small Cell Lung Cancer Progression via Transcription Activation of ITGAL.","authors":"Wen-Tao Wang, Jie Yang, Peng-Fei Jiang","doi":"10.5812/ijpr-159395","DOIUrl":"10.5812/ijpr-159395","url":null,"abstract":"<p><strong>Background: </strong>Recent evidence has demonstrated the crucial role of macrophage polarization in promoting non-small cell lung cancer (NSCLC) progression within the tumor microenvironment.</p><p><strong>Objectives: </strong>This study investigated the possible regulatory mechanism of macrophage polarization during NSCLC development.</p><p><strong>Methods: </strong>The proportion of M1/M2 macrophages was examined by flow cytometry. The expression of macrophage markers and target molecules was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical staining. Non-small cell lung cancer cells were treated with conditioned medium (CM) from THP-1 macrophages. Cell counting kit-8 (CCK-8), scratch, and transwell assays were used to assess NSCLC cell growth and metastasis. Gene promoter activity was evaluated by dual-luciferase reporter assay. A xenograft model was adopted to determine NSCLC growth in vivo.</p><p><strong>Results: </strong>Histone-lysine N-methyltransferase 2D (KMT2D) and integrin subunit alpha L (ITGAL) were lowly expressed in NSCLC tissues and cells. The KMT2D overexpression facilitated the polarization of macrophages from M2 to M1 type, which repressed the growth, migration, and invasion of NSCLC cells. Mechanistically, KMT2D promoted the transcription and expression of ITGAL. Inhibition of ITGAL abrogated KMT2D overexpression-mediated M1 macrophage polarization and its anti-cancer effects on NSCLC.</p><p><strong>Conclusions: </strong>The KMT2D transcriptionally activated ITGAL to trigger M1 macrophage polarization, thereby delaying NSCLC progression. Our findings suggest KMT2D as a potential therapeutic target for NSCLC.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e159395"},"PeriodicalIF":1.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730969","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}