{"title":"Innovative Peptide Therapeutics for SARS-CoV-2: Design, Docking, and Functional Analysis.","authors":"Samaneh Karimkhanilouei, Saeid Ghorbian, Sanaz Mahmazi, Changiz Ahmadizadeh, Keivan Nedaei","doi":"10.5812/ijpr-160762","DOIUrl":"10.5812/ijpr-160762","url":null,"abstract":"<p><strong>Background: </strong>The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates the rapid development of novel therapeutics, particularly those targeting conserved viral proteins. Peptide-based drugs offer high specificity and low toxicity, making them ideal candidates.</p><p><strong>Objectives: </strong>This study employed an integrated computational approach, combining structural biology, molecular docking, and molecular dynamics (MD) simulations, to design and evaluate novel peptide analogs targeting three key proteins of SARS-CoV-2: the Spike (S) protein, RNA-dependent RNA polymerase (RdRp), and nucleocapsid (N) protein.</p><p><strong>Methods: </strong>The first step involved preparing a dataset containing anti-SARS-CoV-2 peptides using the DRAVP database and a literature survey. Then, the best inhibitory peptides were screened using the AVPPred tool, and analogous peptides were designed based on the selected lead peptide. The designed peptides were then investigated in terms of their structure, physicochemical properties, and antiviral potency. Additionally, molecular docking, performed using the specialized nCoVDock2 server, showed that all designed analogs exhibited highly favorable binding. Specifically, the best-performing analogs achieved remarkable docking scores in the range of -200 to -300 a.u. (arbitrary units), indicating a strong predicted relative binding affinity for their respective targets. The top-ranked complexes were then subjected to 100 ns explicit solvent MD simulations.</p><p><strong>Results: </strong>Our findings suggest that peptide W is the most effective analogue for inhibiting S protein, achieving a relative docking score of -303.41 a.u., in contrast to the -284.12 a.u. relative docking score of the EK1 lead peptide. Regarding the inhibition of RdRp protein, the top newly designed analogue is peptide A5, which has a relative docking score of -187.36 a.u., compared to the score of -121.3 a.u. for lead peptide 5, respectively. The leading novel analogue for inhibiting the N protein is A7, which has a relative docking score of -317.69 a.u., surpassing the relative docking score of -255.48 a.u. for Plectasin. The MD results confirmed the high dynamic stability of the W (targeting S protein) and A5 (targeting RdRp) complexes, demonstrating low Root Mean Square Deviation (RMSD) and maintaining critical hydrogen bonds and hydrophobic interactions throughout the trajectory.</p><p><strong>Conclusions: </strong>The use of bioinformatics algorithms to develop engineered peptides with high affinity for SARS-CoV-2 virulence proteins offers a promising outlook for peptide-based therapies against SARS-CoV-2. It also presents a promising approach for developing therapeutic methods against other viral diseases. Furthermore, these computational insights lay the groundwork for subsequent in vitro and in vivo validation studies to ascertain the therapeutic efficacy and saf","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e160762"},"PeriodicalIF":1.8,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306181","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":"Pharmaceutical Utilization Review: A Five-Year Time Trend Analysis of the Pharmaceutical Market in Iran.","authors":"Mohammadamir Nemati, Behzad Fatemi, Fatemeh Soleymani, Meysam Seyedifar, Donya Zali, Zahra Shahali, Hossein Ranjbaran","doi":"10.5812/ijpr-158927","DOIUrl":"10.5812/ijpr-158927","url":null,"abstract":"<p><strong>Background and objectives: </strong>The primary objective of this study was to compare the total and insurance-covered utilization of pharmaceuticals in Iran from March 2018 to March 2023. The findings of this study can offer valuable insights to healthcare professionals, researchers, and policymakers to make informed decisions.</p><p><strong>Methods: </strong>A retrospective cross-sectional study in Iran examined drug utilization patterns (specific databases, e.g., Iranian Health Insurance Organization and Social Security Organization) using Joinpoint regression. The study calculated the Defined Daily Doses per 1000 inhabitants per day (DID) for each medicine based on the anatomical therapeutic chemical/defined daily dose (ATC/DDD) system. All medicines with valid ATC/DDD assignments available during 2018 - 2023 were included to ensure comprehensive national coverage rather than a selected sample. Joinpoint regression was employed for trend analysis, focusing on annual and monthly percent changes in pharmaceutical utilization. Statistical analysis was conducted using MS Excel and Joinpoint software, with significance set at P-value < 0.05.</p><p><strong>Results: </strong>The study assessed 1185 ATC codes, out of which 751 were found eligible for analysis. Among these, 728 were covered by two major Iranian insurance organizations. The study found that the share of insurance utilization of these pharmaceuticals ranged from 27 to 48 percent. The trend utilization showed significant increases in overall utilization in classes C, J, L, N, and P. The utilization trends under insurance coverage revealed that classes L, R, and S showed a significant increase. After the implementation of the Daruyar Plan and the removal of the preferred currency exchange rate for all classes, there has been an increase in utilization under insurance coverage.</p><p><strong>Conclusions: </strong>This study reveals notable patterns and discrepancies in utilization levels within different drug classes, as well as the impact of insurance coverage and the Daruyar Plan on medication utilization.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e158927"},"PeriodicalIF":1.8,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306194","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 the Effects of Sevoflurane and Isoflurane During Liver Transplant Surgery on the Short-Term Cardiac, Hepatic, and Renal Outcome: A Randomized Clinical Trial.","authors":"Mohammadreza Moshari, Sadaf Tahery, Mastaneh Dahi Taleghani, Shide Dabir, Maryam Vosoughian, Soudeh Tabashi, Mohsen Ariannik, Firoozeh Madadi","doi":"10.5812/ijpr-166290","DOIUrl":"10.5812/ijpr-166290","url":null,"abstract":"<p><strong>Background: </strong>Liver transplantation is frequently complicated by ischemia-reperfusion injury (IRI), which may impair hepatic, renal, and cardiac function. Volatile anesthetics such as isoflurane and sevoflurane are believed to mitigate this injury.</p><p><strong>Objectives: </strong>This study aimed to compare their effects on short-term organ outcomes in deceased donor liver transplant recipients.</p><p><strong>Methods: </strong>In this study, 70 liver transplantation candidates at Taleghani Hospital in Tehran were enrolled after obtaining informed consent, and various variables were assessed before, during, and at two intervals immediately after surgery and one week post-operation. Patients were randomly allocated to receive either isoflurane or sevoflurane for anesthesia maintenance using the sealed opaque envelope technique for allocation concealment. Randomization was performed by a study nurse not involved in patient care using computer-generated random numbers. The primary outcome was defined as the postoperative peak serum alanine aminotransferase (ALT) level. Secondary outcomes included peak aspartate aminotransferase (AST), total bilirubin, creatinine, troponin I, C-reactive protein (CRP), intraoperative blood product requirements (packed red blood cells and fresh frozen plasma), hemodynamic parameters, and urine output.</p><p><strong>Results: </strong>Baseline characteristics were comparable between groups. No significant differences were found in intraoperative hemodynamics or postoperative laboratory values of liver and renal function (P > 0.05). Postoperative liver enzyme levels increased in both groups following reperfusion, consistent with IRI. However, no statistically significant differences were observed between the isoflurane and sevoflurane groups in peak serum ALT levels, measured 6 hours after reperfusion and on postoperative day 7 (P > 0.05 for all comparisons). Similarly, AST levels did not differ significantly between groups at any postoperative time point. Renal and cardiac biomarkers, including creatinine and troponin I, were also comparable between groups. In contrast, patients receiving sevoflurane required significantly higher volumes of packed red blood cells and fresh frozen plasma intraoperatively compared with the isoflurane group (P < 0.05).</p><p><strong>Conclusions: </strong>The results obtained in this study showed that the use of isoflurane and sevoflurane did not have a significant difference in the severity of ischemic reperfusion injury caused after liver transplantation surgery on the liver, kidney, and heart; also, in this study, the functional conditions of these organs during and after surgery were evaluated, and by examining at different time intervals, these two inhalation anesthetics did not have a different effect on the short-term outcome of patients after receiving a liver transplant.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e166290"},"PeriodicalIF":1.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306206","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":"Effect of Lemon Inhalation Aromatherapy on Postoperative Pain, Nausea and Vomiting, Delirium, and Inflammatory Markers After Coronary Artery Bypass Grafting: A Triple-Blind Randomized Trial.","authors":"Siavash Sangi, Seyed Mohammadreza Amouzegar Zavareh, Hedayat Sahraei, Mojtaba Sepandi, Alireza Moradi","doi":"10.5812/ijpr-168770","DOIUrl":"10.5812/ijpr-168770","url":null,"abstract":"<p><strong>Background: </strong>Complementary and integrative medicine has gained increasing attention as a safe adjunct for improving postoperative outcomes, particularly in cardiac surgery where pain, postoperative nausea and vomiting (PONV), and delirium remain common and debilitating complications.</p><p><strong>Objectives: </strong>This randomized clinical trial aimed to investigate the effect of lemon inhalation aromatherapy on postoperative pain, PONV, delirium, and inflammatory markers in patients undergoing coronary artery bypass grafting (CABG) surgery.</p><p><strong>Methods: </strong>In this triple-blind, parallel-group randomized controlled trial, 104 adult patients scheduled for elective CABG surgery were randomly allocated to either lemon aromatherapy or an odorless placebo. Aromatherapy began the evening before surgery, was administered every two hours until anesthesia induction, and resumed continuously during mechanical ventilation and for 72 hours after extubation. Pain and PONV were assessed every 6 hours across eight postoperative shifts using a 0 - 10 Numeric Rating Scale. Delirium was evaluated at 24, 48, and 72 hours using the intensive care delirium screening checklist (ICDSC). Inflammatory markers [C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR)] were measured at baseline and 72 hours. Data were entered after double-checking into SPSS version 26. Continuous variables were tested for normality using the Shapiro-Wilk test; normally distributed variables were compared using independent <i>t</i>-tests, and non-normal variables with the Mann-Whitney U test. Categorical variables were analyzed using chi-square or Fisher's exact test. All analyses were two-tailed with a significance level of P < 0.05.</p><p><strong>Results: </strong>Of the 104 randomized patients, 103 completed the study (one patient in the intervention group was withdrawn due to postoperative cerebrovascular insult). The two groups were well-balanced at baseline with respect to demographic and clinical characteristics. Pain scores were significantly lower in the intervention group at all eight postoperative shifts (P < 0.001). Postoperative nausea and vomiting severity was significantly reduced across all shifts (P < 0.001), with fewer vomiting episodes and lower need for rescue antiemetic medications. The incidence of delirium was significantly lower in the intervention group at 24 hours (11.8% vs. 28.8%), 48 hours (15.7% vs. 34.6%), and 72 hours (7.8% vs. 23.1%) (all P < 0.05). Significant improvements were also observed in multiple ICDSC subscales, particularly inattention, disorientation, sleep-wake disturbances, and inappropriate speech/mood. At 72 hours, both CRP and NLR levels were significantly lower in the aromatherapy group, suggesting attenuation of the postoperative inflammatory response. No aromatherapy-related adverse events were observed.</p><p><strong>Conclusions: </strong>Lemon inhalation aromatherapy was effective in significant","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168770"},"PeriodicalIF":1.8,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306254","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}
Umar Saeed, Zahra Zahid Piracha, Andromeda M Nauli, Surya M Nauli
{"title":"Dual TYK2/JAK1 Inhibition by Brepocitinib Reprograms Synoviocyte Pathobiology: Mechanistic Insights Into Targeted Therapy for Rheumatoid Arthritis.","authors":"Umar Saeed, Zahra Zahid Piracha, Andromeda M Nauli, Surya M Nauli","doi":"10.5812/ijpr-166019","DOIUrl":"10.5812/ijpr-166019","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, persistent inflammation, and joint destruction. Targeted inhibition of intracellular signaling pathways, such as JAK-STAT, has improved RA treatment outcomes, though safety and selectivity remain as concerns. Brepocitinib, a dual TYK2/JAK1 inhibitor, has shown clinical efficacy in the management of autoimmune diseases, yet its mechanistic impact on synoviocytes remains underexplored.</p><p><strong>Objectives: </strong>To investigate the molecular and functional effects of brepocitinib on MH7A and RA-FLS synoviocytes, a key effector cell type in RA pathogenesis.</p><p><strong>Methods: </strong>MH7A and RA-FLS cells were treated with brepocitinib (0.5 µM, 1 µM, and 5 µM) for 24 hours. Cell viability was assessed. Western blotting was used to examine phosphorylation of TYK2, JAK1, STAT1/3, and apoptotic markers (BAX, BCL-2, caspase-3). Quantitative PCR and ELISA were performed to evaluate mRNA and protein levels, respectively, of IL-6, TNF-α, and IFN-γ. Wound healing assays measured synoviocyte migration.</p><p><strong>Results: </strong>Brepocitinib maintained ≥ 85% cell viability across all doses, compared with ~20% viability in doxorubicin-treated controls. At 5 µM, phosphorylation of JAK1 and STAT3 was suppressed by > 80%, while TYK2 and STAT1 inhibition reached ~70%. IL-6 and TNF-α transcripts were reduced by > 80% and IFN-γ by ~70%, with corresponding decreases in secreted cytokines (IL-6: 100 pg/mL to 20 pg/mL; TNF-α: 150 pg/mL to 15 pg/mL; IFN-γ: 41 pg/mL to 11 pg/mL). Brepocitinib shifted the BAX/BCL-2 ratio fourfold in favor of apoptosis and increased cleaved caspase-3 levels to ~80% of maximal response. Functionally, it reduced wound closure from ~75% in controls to ~20% at 5 µM, confirming potent inhibition of synoviocyte migration.</p><p><strong>Conclusions: </strong>Brepocitinib exerts multi-faceted effects on RA synoviocytes by simultaneously inhibiting inflammatory signaling, suppressing cytokine expression, restoring apoptotic sensitivity, and reducing migratory potential. These findings provide mechanistic support for brepocitinib as a targeted therapeutic agent in RA.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e166019"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306262","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}
Wei Meng, Zahra Zahid Piracha, Umar Saeed, Dilber Uzun Ozsahin, Ilker Ozsahin, Yongwei Tao, Zhanping Ren
{"title":"MEK1/2 Inhibitor (U0126) and PI3K Inhibitor (LY294002) Suppress Herpes Simplex Virus Type 1 Replication by Targeting MAPK/ERK1/2 and PI3K/AKT Signaling Pathways: Implications for Oral Health and Translational Control of Orolabial HSV-1 Infection.","authors":"Wei Meng, Zahra Zahid Piracha, Umar Saeed, Dilber Uzun Ozsahin, Ilker Ozsahin, Yongwei Tao, Zhanping Ren","doi":"10.5812/ijpr-164639","DOIUrl":"10.5812/ijpr-164639","url":null,"abstract":"<p><strong>Background: </strong>Current antivirals for orolabial Herpes simplex virus type 1 (HSV-1) often provide incomplete suppression and limited reactivation control, sustaining recurrent oral lesions and inflammation that compromise oral health. HSV-1 subverts host signaling networks to enhance its replication and trigger inflammation. Among these, the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways are hijacked to facilitate viral gene expression and cell survival.</p><p><strong>Objectives: </strong>In this study, we employed U0126 [a mitogen-activated protein kinase 1/2 (MEK1/2) inhibitor] and LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor] as targeted pharmacological tools to intercept HSV-1's exploitation of host keratinocyte signaling.</p><p><strong>Methods: </strong>Human HaCaT keratinocytes were infected with HSV-1 and treated with U0126 or LY294002. Western blotting was used to assess phosphorylation of ERK1/2 and activation of protein kinase B (AKT). MTT assays were performed to evaluate cell viability. Real-time PCR was utilized to quantify viral transcripts (ICP0, ICP4, gB, and gC) and inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)]. Confocal microscopy was employed to visualize the intracellular distribution of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), phosphorylated activation of protein kinase B (p-AKT), and HSV-1 glycoprotein D (gD). Viral titers were determined using plaque assays.</p><p><strong>Results: </strong>The HSV-1 infection induced a time-dependent increase in phosphorylation of ERK1/2 and AKT, with p-ERK1/2 peaking at 12 h and p-AKT increasing 2.5-fold by 24 h. Cell viability declined from 100% at baseline to 45% at 24-hours post-infection (hpi). Treatment with U0126 and LY294002 reduced p-ERK1/2 and p-AKT levels to 25% and 30% of infected controls, respectively, restoring viability to 82 - 86%. Both inhibitors markedly suppressed viral gene expression (ICP0, ICP4, gB, gC down by 60 - 80%) and inflammatory cytokines (IL-6 and TNF-α reduced by > 50%). Plaque assays showed a strong decline in infectious titers - from 175 plaques per well in untreated infection to 60 and 45 plaques after U0126 and LY294002, respectively. Confocal imaging further revealed diminished nuclear accumulation of p-ERK1/2 and p-AKT, indicating disruption of post-entry signaling critical for viral replication.</p><p><strong>Conclusions: </strong>Targeting host signaling bottlenecks with U0126 and LY294002 offers a dual-pronged antiviral strategy against HSV-1 by dismantling the ERK/AKT axis critical for replication and inflammatory amplification. These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e164639"},"PeriodicalIF":1.8,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306110","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":"Quercetin-Loaded Avocado Oil Nanoemulsion Reverses High-fat and High-carbohydrate Diet-Induced Testicular Dysfunction: Role of Oxidative Stress and NPY Signaling in a Randomized Trial.","authors":"Hamidreza Mazangi, Negar Panahi, Saeed Hesaraki, Shahabeddin Safi","doi":"10.5812/ijpr-165025","DOIUrl":"https://doi.org/10.5812/ijpr-165025","url":null,"abstract":"<p><strong>Background: </strong>High-fat and high-carbohydrate diets (HF) can negatively affect male reproductive function, impairing spermatogenesis and testosterone production. Quercetin (Qu) may mitigate testicular damage, but its effectiveness is limited by poor bioavailability. Avocado oil (AO) improves blood lipid levels and enhances the absorption of fat-soluble nutrients.</p><p><strong>Objectives: </strong>We explore the impact of AO combined with quercetin on weight gain, dyslipidemia, hormonal dysregulation, testicular oxidative stress, and NPY signaling, all induced by a HF diet, to highlight testicular dysfunction and metabolic disorders.</p><p><strong>Methods: </strong>A nanoemulsion of avocado oil containing quercetin (NAOQu) was developed as an oil-in-water (O/W) nanoemulsion, utilizing the hydrophilic-lipophilic balance (HLB) value and conducting stability assessments, followed by characterization (DLS, Zeta potential, and TEM). Thirty rats were fed an HF diet for 8 weeks and treated with either Qu, a nanoemulsion of avocado oil (NAO), or NAOQu. Body weight was determined, and serum was analyzed for triglycerides (TG), cholesterol, HDL, and testosterone levels. Testicular homogenates were assessed for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) activity, and cholesterol. Hypothalamic NPY mRNA expression was quantified using qPCR.</p><p><strong>Results: </strong>The NAOQu (1% Qu, 1:1 avocado: Coconut oil) exhibited a stable, spherical morphology with a particle size of 286.7 nm, a zeta potential of -25.8 mV, and enhanced physical stability. The NAOQu significantly reduced body weight, improved lipid profiles (lowering TG and cholesterol while increasing HDL), and restored testosterone levels by 85% compared to high-fat diet (HFD) controls and reduced testicular MDA by 62% while increasing GSH and SOD activities by 2.3-fold and 1.8-fold, respectively. Molecular analyses revealed decreased testicular cholesterol levels and downregulated NPY mRNA expression, indicating reduced metabolic stress.</p><p><strong>Conclusions: </strong>The combined NAOQu formulation showed greater protective effects than Qu or AO alone, suggesting a synergistic effect. These findings highlight the potential of avocado oil-based nanoemulsion as an effective delivery system for Qu, offering a novel therapeutic strategy to counteract HF-induced male reproductive dysfunction and metabolic disease.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e165025"},"PeriodicalIF":1.8,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226818","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 GRP78/ATF6/IRE1 and Caspase-12 Signaling Pathways in the Protective Effects of n-Hexane Oil Extract of Black Soldier Flies' Larvae (<i>Hermetia illucens</i>) Against Aflatoxin-Induced Hepatotoxicity in Rats.","authors":"Fateme Heidari, Tahereh Zarei Taher, Yalda Arast","doi":"10.5812/ijpr-167846","DOIUrl":"https://doi.org/10.5812/ijpr-167846","url":null,"abstract":"<p><strong>Background: </strong>Global contamination of agricultural products with aflatoxin (AF) is one of the most important concerns in the field of food safety and quality. Aflatoxin, when entering the food chain, can cause oxidative stress and hepatotoxicity. Black soldier fly larvae (BSFL) are an environmentally friendly insect whose extract is rich in valuable bioactive compounds with antioxidant properties.</p><p><strong>Objectives: </strong>This study aimed to investigate the protective effect of the n-hexane extract of BSFL on oxidative stress, inflammation, and histopathological changes caused by Aflatoxin B1 (AFB1)-induced hepatotoxicity in rats.</p><p><strong>Methods: </strong>Thirty-five male Wistar rats with a weight range of 200 to 250 g were randomly divided into 5 equal groups including Control, AFB1 (75 μg/kg), BSFL (360 mg/kg), BSFL 180 mg/kg+AFB1, and BSFL 360 mg/kg+AFB1. At the end of the treatment on the twenty-eighth day, the animals were euthanized and samples were taken for liver enzymes, oxidative stress, inflammation, endoplasmic reticulum (ER) stresses, apoptosis marker, histopathology, and expression of ER stress-related proteins analyses. Data were analyzed by one-way ANOVA followed by Tukey's post-hoc test, with P < 0.05 considered statistically significant.</p><p><strong>Results: </strong>According to the results of the study, AFB1 administration significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) (P < 0.001) and also decreased the levels of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) compared to the control group (P < 0.001). These biochemical and inflammatory abnormalities caused by AFB1 were confirmed by histopathological observations of liver tissue. Administration of BSFL extract (at the higher dose of 360 mg/kg) resulted in significant reversal of biochemical, inflammatory, and hepatic markers and modulated GRP78/ATF6/IRE1 signaling in AF-poisoned rats. Our histological results showed that BSFL extract (360 mg/kg) could reduce steatosis, cellular swelling, and lobular inflammation induced after AF exposure.</p><p><strong>Conclusions: </strong>The results of this study indicate that BSFL extract, as a valuable bioactive substance with antioxidant properties, may attenuate biochemical indices, oxidative stress, and inflammation caused by AF-induced hepatotoxicity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e167846"},"PeriodicalIF":1.8,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226874","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":"Evaluating the Impact of Strategic Alignment on Performance Components of Iranian Pharmaceutical Companies Using Machine Learning Techniques.","authors":"Simin Sadeghi, Mahdi Mohammadzadeh","doi":"10.5812/ijpr-165722","DOIUrl":"https://doi.org/10.5812/ijpr-165722","url":null,"abstract":"<p><strong>Background: </strong>Sustainable performance in the pharmaceutical industry hinges on the strategic alignment of human resources (HR), marketing, and information technology (IT). Prior studies often examined these domains separately; evidence on their joint influence in Iran's pharmaceutical sector remains limited.</p><p><strong>Objectives: </strong>To assess how HR, marketing, and IT strategic alignment relate to profitability, liquidity, and revenue growth using machine-learning methods, and to document model generalization and measurement validity.</p><p><strong>Methods: </strong>This applied, cross-sectional study surveyed 323 managers in Tehran Stock Exchange (TSE)-listed pharmaceutical firms (May to Nov, 2024). A validated questionnaire [CVI/CVR; EFA/ confirmatory factor analysis (CFA); reliability reported] was used only to construct composite indices of HR, marketing, and IT alignment; organizational performance outcomes, profitability, liquidity, and revenue growth (year-over-year) were computed from audited financial statements and then z-standardized. Inputs were min-max scaled to [0, 1]. A feed-forward artificial neural network (ANN; 3-15-1 per outcome; ReLU hidden, linear output) was trained with Levenberg-Marquardt, early stopping, and L2 regularization. Data were split 70/15/15 (train/validation/test) with 5 × 10 repeated cross-validation; bootstrap resampling (B = 1000) produced BCa 95% CIs. Model performance was assessed using mean squared error (MSE), mean absolute error (MAE), root mean square error (RMSE), and R<sup>2</sup>.</p><p><strong>Results: </strong>Aggregate fit was strong (R<sup>2</sup> = 0.91; RMSE = 0.134), with comparable validation/test metrics indicating good generalization. The triadic alignment factor showed the highest association with overall strategic alignment (R<sup>2</sup> = 0.76; P < 0.001). At the subcomponent level, organizational commitment related to profitability (R<sup>2</sup> = 0.59), and aggressive marketing to profitability (R<sup>2</sup> = 0.66). Results are associative, not causal.</p><p><strong>Conclusions: </strong>Machine-learning evidence suggests that coordinated alignment across HR, marketing, and IT is strongly associated with key performance components. The validated instrument, explicit splits, cross-validation, and bootstrap CIs enhance robustness and provide a practical, data-driven framework for managerial action in Iran's pharmaceutical industry.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e165722"},"PeriodicalIF":1.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226913","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}