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1 Quercetin Induces Macrophage Polarization through PI3K-AKT Pathway in Atherosclerosis: Network Pharmacology, Molecule Docking and in vitro Analysis https://brieflands.com/journals/ijpr/articles/168202 10.5812/ijpr-168202 1 Background :Quercetin (QU) is a major flavonoid in multiple herbs with wide biological effects, while its role in preventing atherosclerosis progression remains largely unknown. Objectives :In this study, we aimed to uncover the effect and underlying mechanism of QU in treating atherosclerosis. Methods :Network pharmacology and protein-protein interaction analysis were conducted to predict potential targets of QU in treating atherosclerosis. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Cell viability, apoptosis, and cell cycle assays were conducted to evaluate the biological effects of QU on atherosclerosis-associated macrophages. Genome expression sequencing (RNA-seq) was performed to identify differentially expressed genes and regulated pathways after QU treatments. Macrophage differentiation and fluorescence-activated cell sorting (FACS), western blot, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were further performed to verify the results of RNA-seq and the effects of QU on regulating the indicated pathway. Results :In this study, 180 potential targets were identified by network pharmacology analysis, and multiple anti-inflammatory pathways were enriched in QU treating atherosclerosis. Our data also indicated that QU promotes macrophage cell viability by reducing cell apoptosis and cell cycle arrest in an atherosclerosis-associated macrophage cell model. Additionally, RNA-seq revealed that the PI3K-AKT pathway might be the significantly upregulated pathway after QU treatment in macrophages to induce M2 polarization, which was further verified by protein and RNA detection. Conclusions :Taken together, we are the first to combine multiple database analyses and genome expression data to uncover the protective effect of QU in treating atherosclerosis by inducing M2 polarization through regulating the PI3K-AKT pathway. 1 14 Li Wang The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China China wangli257@mail.sysu.edu.cn Yifan Han The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China China hanyifan923@163.com Yuyu Lei Qinghai University, Xining, China China leiyuyu0621@163.com Jingfeng Liu Peking University Shenzhen Hospital, Shenzhen, China China oscar1356@smu.edu.cn Jiajun Yu The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China China yjjzdby@foxmail.com Guiyu Li The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China China ligy57@mail.sysu.edu.cn No Keyword 1.pdf [0]Wang L, Huang S, Liang X, Zhou J, Han Y, He J, et al.Immuno-modulatory role of baicalin in atherosclerosis prevention and treatment: current scenario and future directions. 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1 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 https://brieflands.com/journals/ijpr/articles/166290 10.5812/ijpr-166290 1 Background :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. Objectives :This study aimed to compare their effects on short-term organ outcomes in deceased donor liver transplant recipients. Methods :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. Results :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). Conclusions :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. 1 8 Mohammadreza Moshari Department of Anesthesiology, Anesthesiology Research Center, School of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran rmoshari@yahoo.com Sadaf Tahery Department of Anesthesiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran sadaf.tahery@gmail.com Mastaneh Dahi Taleghani Department of Anesthesiology, Anesthesiology Research Center, School of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran ma_dahi@yahoo.com Shide Dabir Department of Anesthesiology, Anesthesiology Research Center, School of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran shdabir@yahoo.com Maryam Vosoughian Department of Anesthesiology, Anesthesiology Research Center, School of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran maryam.vosoghian@yahoo.com Soudeh Tabashi Department of Anesthesiology, Anesthesiology Research Center, School of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran soodeh.tabashi@yahoo.com Mohsen Ariannik Department of Anesthesiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran mnannk@gmail.com Firoozeh Madadi Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Department of Anesthesiology, Ayatollah Taleghani Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Iran fmadadi33@gmail.com No Keyword 2.pdf [0]Wang S, Toy M, Hang Pham TT, So S.Causes and trends in liver disease and hepatocellular carcinoma among men and women who received liver transplants in the U.S., 2010-2019. 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[PubMed ID: 30548879]. doi: 10.1002/jcb.27368.##[13]Crowley H, Lewis WD, Gordon F, Jenkins R, Khettry U.Steatosis in donor and transplant liver biopsies. Hum Pathol. 2000;31(10):1209-13. [PubMed ID: 11070113]. doi: 10.1053/hupa.2000.18473.##[14]Ijaz S, Yang W, Winslet MC, Seifalian AM.Impairment of hepatic microcirculation in fatty liver. Microcirculation. 2003;10(6):447-56. [PubMed ID: 14745457]. doi: 10.1038/sj.mn.7800206.##[15]Peralta C, Brenner C.Endoplasmic reticulum stress inhibition enhances liver tolerance to ischemia/reperfusion. Curr Med Chem. 2011;18(13):2016-24. [PubMed ID: 21517773]. doi: 10.2174/092986711795590039.##[16]Selzner N, Rudiger H, Graf R, Clavien PA.Protective strategies against ischemic injury of the liver. Gastroenterology. 2003;125(3):917-36. [PubMed ID: 12949736]. doi: 10.1016/s0016-5085(03)01048-5.##[17]Jimenez-Castro MB, Cornide-Petronio ME, Gracia-Sancho J, Peralta C.Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury. Cells. 2019;8(10). [PubMed ID: 31547621]. [PubMed Central ID: PMC6829519]. doi: 10.3390/cells8101131.##[18]Cai Z, Suo L, Huang Z.Isoflurane Suppresses Proliferation, Migration, and Invasion and Facilitates Apoptosis in Colorectal Cancer Cells Through Targeting miR-216. Front Med. 2021;8:658926. [PubMed ID: 34458282]. [PubMed Central ID: PMC8385302]. doi: 10.3389/fmed.2021.658926.##[19]Taylor B, Scott TE, Shaw J, Chockalingam N.Renal safety of critical care sedation with sevoflurane: a systematic review and meta-analysis. J Anesth. 2023;37(5):794-805. [PubMed ID: 37498387]. doi: 10.1007/s00540-023-03227-y.##[20]Park M, Jung K, Cho HS, Min JJ.Renal injury from sevoflurane in noncardiac surgery: a retrospective cohort study. Br J Anaesth. 2022;129(2):182-90. [PubMed ID: 35688659]. doi: 10.1016/j.bja.2022.04.026.##[21]Ma H, Yang B, Yu L, Gao Y, Ye X, Liu Y, et al.Sevoflurane protects the liver from ischemia-reperfusion injury by regulating Nrf2/HO-1 pathway. Eur J Pharmacol. 2021;898:173932. [PubMed ID: 33631180]. doi: 10.1016/j.ejphar.2021.173932.##[22]Sondekoppam RV, Narsingani KH, Schimmel TA, McConnell BM, Buro K, Ozelsel TJ.The impact of sevoflurane anesthesia on postoperative renal function: a systematic review and meta-analysis of randomized-controlled trials. Can J Anaesth. 2020;67(11):1595-623. [PubMed ID: 32812189]. doi: 10.1007/s12630-020-01791-5.##[23]Zhang K, Xu X, Hu L.Sevoflurane attenuates hepatic ischemia reperfusion injury by the miR-122/Nrf2 pathway. Ann Transl Med. 2022;10(6):350. [PubMed ID: 35433991]. [PubMed Central ID: PMC9011315]. doi: 10.21037/atm-22-115.##[24]Beck-Schimmer B, Bonvini JM, Schadde E, Dutkowski P, Oberkofler CE, Lesurtel M, et al.Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial. Transplantation. 2015;99(8):1606-12. 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1 Wedelolactone Inhibits Hepatitis B Virus Replication by Modulating NF-κB and Nrf2/HO-1 Signaling: An in-vitro Huh7 1.3-mer HBV Plasmid Model https://brieflands.com/journals/ijpr/articles/168329 10.5812/ijpr-168329 1 Background :Chronic hepatitis B virus (HBV) infection is a well-recognized cause of hepatic injury through prolonged viral replication, inflammation, and oxidative stress. Existing antiviral drugs limit viral replication but cannot eliminate viral transcription or even totally preclude liver injury, thus reemphasizing the significance of drugs with combined antiviral and hepatoprotective effects. Objectives :To evaluate the effects of wedelolactone on HBV replication, gene expression, inflammation, and oxidative stress in an in-vitro model of HBV plasmid transfection with human hepatic cells. Methods :Human hepatocellular carcinoma cells (Huh7) were transfected with a 1.3-mer plasmid and treated with wedelolactone (2.5 - 10 µM). Luciferase assays for HBV promoter activity, Northern blotting and Southern blotting for transcripts and replicative intermediates, qPCR for extracellular HBV DNA, and western blotting for viral antigens such as HBx were performed. Cell cytotoxicity was measured. NF-κB/IκB, inflammatory cytokines (TNF-α, IL-6), and antioxidant markers (Nrf2, HO-1, Keap1) were assessed to evaluate inflammatory and oxidative responses. Results :Wedelolactone significantly suppresses HBV promoter activity, RNAs, core particle formation, and extracellular HBV DNA. It reduced the expression of HBcAg and HBsAg. It inhibited NF-κB activation and cytokine release, while simultaneously enhancing Nrf2/HO-1 signaling, including induction of heme oxygenase-1 by lowering levels of Keap1. Conclusions :Wedelolactone exerts dual antiviral and hepatoprotective actions by inhibiting HBV replication and modulating inflammatory and oxidative stress pathways. 1 14 Bin Wang Department of Hepatology, Public Health Clinical Center Affilliated to Shandong University, Jinan, China China iamlittlebinbin@163.com Xuehui Bu Department of Hepatology, Public Health Clinical Center Affilliated to Shandong University, Jinan, China China buxuehui@126.com Umar Saeed Clinical and Biomedical Research Center (CBRC), Foundation University School of Health Sciences (FUSH), Foundation University, Islamabad, Pakistan Korea University, Seoul, Republic of Korea Pakistan Republic of Korea umarsaeed15@yahoo.com Zahra Zahid Piracha Institute of Graduate Studies and Research, Cyprus International University, Nicosia, Northern Cyprus Széchenyi István University, Győr, Hungary Northern Cyprus Hungary piracha.zahra@gmail.com Di Xiao Department of Hepatology, Public Health Clinical Center Affilliated to Shandong University, Jinan, China China xiaodi791126@sina.com No Keyword 3.pdf [0]World Health Organization.WHO publishes new guidelines on hepatitis B. 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1 Comparative Study on the Effects of Ginseng and Green Tea Extracts on Selected Lipid Metabolism Markers in Adipocyte https://brieflands.com/journals/ijpr/articles/162445 10.5812/ijpr-162445 1 Background :Dietary patterns are effective in obesity treatment. This has led to more investigations on its mechanisms in combating obesity. Objectives :This study investigated the effects of ginseng and green tea extracts (GTE) on selected markers of lipid metabolism and the expression of some related genes in adipocytes. Methods :After a one-month period of consuming a high fatty content diet, a total of 42 male Wistar rats were assigned to seven groups randomly. The rats were then subjected to an eight-week treatment where they were administered different dosages of GTE and ginseng extract (GE) through oral administration. Then, some serologic parameters pertaining to lipid metabolism were analyzed in the treated rats. Furthermore, alterations in the expression levels of select genes, bone morphogenetic protein 7 (BMP7), hormone-sensitive lipase (HSL), and leptin, implicated in lipid metabolism, were quantified within the adipose tissue of the rats utilizing the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methodology. Ultimately, the chemical composition of the extracts was analyzed by high performance liquid chromatography (HPLC). Results :The findings indicated that the utilization of the extracts had a notable impact on the reduction of body weight. There was a noteworthy enhancement of high-density lipoprotein levels across all study groups, as indicated by a statistically significant increase at a confidence level of 95%. The efficacy of the administered extracts was observed in a significant upregulation in BMP7 and HSL gene expression. Conversely, there was a notable reduction in leptin expression, which reached statistical significance at a confidence level of 95%. HPLC results detected 9 ginsenosides in the GE, among which Rb1 (100 mAU) was present in the largest amount, and 9 alkaloids in the GTE, among which epicatechin (EC) (380 mAU) and caffeine (320 mAU) were present in the largest amount. Conclusions :The present study holds the potential to offer novel insights regarding the mechanism through which GE and GTE exert their anti-obesity effects. 1 12 Mandana Salehi Department of Biochemistry, Fal.C., Islamic Azad University, Isfahan, Iran Iran salehi.mandana1389@gmail.com Kahin Shahanipour Department of Biochemistry, Fal.C., Islamic Azad University, Isfahan, Iran Iran shahanipur_k@yahoo.com Ramesh Monajemi Department of Biology, Fal.C., Islamic Azad University, Isfahan, Iran Iran monajemi@iaufala.ac.ir Parisa Mohamadynejad Department of Biology, ShK.C., Islamic Azad University, Shahr-eKord, Iran Iran amoshtaghie@gmail.com No Keyword 4.pdf [0]Chen LH, Chien YW, Liang CT, Chan CH, Fan MH, Huang HY.Green tea extract induces genes related to browning of white adipose tissue and limits weight-gain in high energy diet-fed rat. Food Nutr Res. 2017;61(1):1347480. [PubMed ID: 28804438]. 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1 KIM-1 as an Early Diagnostic Biomarker of Cisplatin-Induced Acute Kidney Injury https://brieflands.com/journals/ijpr/articles/164432 10.5812/ijpr-164432 1 Background :Acute kidney injury (AKI) is a frequent complication of cisplatin chemotherapy, largely due to its toxic accumulation in renal proximal tubules. Current biomarkers show limited sensitivity in early detection, underscoring the need for more specific indicators. Kidney Injury Molecule-1 (KIM-1), upregulated in damaged tubular cells, shows promise as an early and accurate AKI biomarker.Objectives :This multimodal study integrates bioinformatic analyses, in vitro experiments, and a systematic review with meta-analysis to comprehensively evaluate KIM-1 expression, function, and early diagnostic performance. Methods :We analyzed single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data to assess HAVCR1 expression and co-regulated genes in kidney tissue and cisplatin-treated HK-2 cells. Protein interactions were mapped using STRING and Cytoscape. In vitro assays, including quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and Cell Counting Kit-8 (CCK-8), were conducted on cisplatin-treated HK-2 cells. For the systematic review and meta-analysis, a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)–guided search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, and CNKI to identify studies evaluating urinary KIM-1 for early (≤ 24 h) detection of cisplatin-induced AKI. Study eligibility was based on clinical AKI defined by serum creatinine criteria, early KIM-1 measurement, and extractable 2 × 2 diagnostic data. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, and pooled estimates were generated using a bivariate model. Results :Single-cell and bulk RNA-seq analyses revealed that HAVCR1 (KIM-1) is specifically expressed in proximal tubular cells and is upregulated following cisplatin-induced injury. Gene enrichment and protein interaction analyses confirmed its association with epithelial transport and injury response pathways. In vitro, cisplatin treatment led to dose-dependent increases in KIM-1 mRNA and protein levels. Meta-analysis showed that urinary KIM-1 has acceptable diagnostic accuracy (AUC = 0.76; 95% CI: 0.65 - 0.86) as an early biomarker for cisplatin-induced AKI. Conclusions :KIM-1 is a proximal tubule–specific, injury-responsive biomarker that is upregulated early during cisplatin-induced kidney damage. Integrative bioinformatic and experimental analyses underscore its potential for early AKI detection, and the meta-analysis further supports its emerging clinical utility. 1 14 Ai-Hui Jin Ningbo Hospital of Integrated Traditional Chinese and Western Medicine, Ningbo, Zhejiang Province, China China 694294629@qq.com Yan-Jie Zheng Ningbo Hospital of Integrated Traditional Chinese and Western Medicine, Ningbo, Zhejiang Province, China China 260615963@qq.com Chen-Long Xu Ningbo Hospital of Integrated Traditional Chinese and Western Medicine, Ningbo, Zhejiang Province, China China xuchenlong1245@126.com Li Zhou Ningbo Hospital of Integrated Traditional Chinese and Western Medicine, Ningbo, Zhejiang Province, China China zhoulizhejiang@163.com Hao Wang Ningbo Hospital of Integrated Traditional Chinese and Western Medicine, Ningbo, Zhejiang Province, China China wh13819892073@163.com Wen-Juan Wang Ningbo College of Health Sciences, Ningbo, Zhejiang Province, China China 350503813@qq.com No Keyword 5.pdf [0]Ronco C, Bellomo R, Kellum JA.Acute kidney injury. 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1 Innovative Peptide Therapeutics for SARS-CoV-2: Design, Docking, and Functional Analysis https://brieflands.com/journals/ijpr/articles/160762 10.5812/ijpr-160762 1 Background :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. Objectives :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. Methods :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. Results :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. Conclusions :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 safety profiles of the identified peptide candidates. 1 22 Samaneh Karimkhanilouei Department of Biology, Ah.C., Islamic Azad University, Ahar, Iran Iran n.biotechnology@yahoo.com Saeid Ghorbian Department of Biology, Ta.C., Islamic Azad University, Tabriz, Iran Iran saeid.ghorbian@iau.ac.ir Sanaz Mahmazi Department of Biology, Za.C., Islamic Azad University, Zanjan, Iran Iran sanazmahmazi@iauz.ac.ir Changiz Ahmadizadeh Department of Biology, Ah.C., Islamic Azad University, Ahar, Iran Iran ch-ahmadizadeh@iau-ahar.ac.ir Keivan Nedaei Department of Medical Biotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Iran nedaee.k@gmail.com No Keyword 6.pdf [0]Cui J, Li F, Shi ZL.Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181-92. [PubMed ID: 30531947]. 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1 Determining Modern Marketing Mix Elements and Their Measurement Indicators for Selling Cosmetic and Health Products in Iranian Pharmacies: A Descriptive-Analytical Cross-sectional Study https://brieflands.com/journals/ijpr/articles/166280 10.5812/ijpr-166280 1 Background :The cosmetic and health products market is a competitive market. Traditional marketing elements do not respond to the market, and the use of modern marketing mixes is necessary for sales success. With the increase in the number of pharmacies in Iran, they are forced to use modern marketing mix elements for this purpose Objectives :The present study aims to identify and define modern marketing mix elements and their measurement indicators that are effective on the sale of cosmetic and health products. Methods :The research method is conducted as a descriptive-analytical cross-sectional study. The statistical population consists of two groups. The first group is experts to determine modern marketing mix elements and the validity of their items, who have been identified and selected with the Snowball method. The second group is customers in Iranian pharmacies. In the experts' point of view, mix elements are determined using the fuzzy Delphi method, and the validity of their elements and items is determined using content and face validity assessment. Subsequently, the effect of the determined factors in Iranian pharmacies is determined using factor analysis of structural equations, and the validity and reliability of their measurement indicators are confirmed (Cronbach's alpha and composite reliability obtained were higher than 0.7). Results :The results indicated that out of the twelve elements of the modern marketing mixes, the seven elements of price, quality, attractiveness, brand image, emotions, advertising, and customer trust are effective elements on the sale of cosmetic and health products, for which measurement indicators have been proposed in the market. The model showed an acceptable fit with CFI values above 0.93, indicating good consistency between the model and the observed data, and path analysis showed that price (β = 0.78), product quality (β = 0.75), and emotional appeal (β = 0.75) had the strongest positive effects on cosmetic and hygiene product sales. Conclusions :This study highlights that traditional marketing mix elements are insufficient to explain customer behavior in the competitive cosmetic and hygienic products market in Iran. Instead, seven modern marketing mix elements (price, quality, attractiveness, brand image, emotions, advertising, and customer trust) play a crucial role in shaping customer satisfaction and purchasing decisions. 1 8 Reza Yaghoubi Nezhad Student Research Committee, Faculty of Pharmacy , Tehran University of Medical Science , Islamic Azad university , Tehran , Iran Iran rrrryaghoubi@gmail.com Majid Annabi Department of Pharmacoeconomics, Faulty of Pharmacy, Tehran Medical Sciences, Islamic Azad university, Tehran, Iran Iran m.annabi@iautmu.ac.ir Amin Akbari Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran Iran aminakbari88@gmail.com Yasaman Bastami Student Research Committee, Faculty of Pharmacy , Tehran University of Medical Science , Islamic Azad University , Tehran , Iran Iran yasamanbastami1380@gmail.com Mahdi Maleki Zadeh Student Research Committee, Faculty of Pharmacy , Tehran University of Medical Science , Islamic Azad University , Tehran , Iran Iran mahdimaleki0180@gmail.com No Keyword 7.pdf [0]Leonidou CN, Katsikeas CS, Morgan NA.“Greening” the marketing mix: do firms do it and does it pay off? J Acad Market Sci. 2012;41(2):151-70. doi: 10.1007/s11747-012-0317-2.##[1]Harini S, Yuningsih E, Gemina D. Enhancing competitiveness of creative industry strategy with resource-based marketing mix. 2nd International Seminar on Business, Economics, Social Science and Technology (ISBEST 2019). 2020.##[2]Sang-Hyeon Y, Myung Soo K, Sang-Yeon S.The Growth and Change of Korean Cosmetics Market in Distribution Structure. J Distribution Sci. 2020;18(1):5-13. doi: 10.15722/jds.18.1.202001.5.##[3]Brkanlić S, Sánchez-García J, Esteve EB, Brkić I, Ćirić M, Tatarski J, et al.Marketing Mix Instruments as Factors of Improvement of Students’ Satisfaction in Higher Education Institutions in Republic of Serbia and Spain. Sustainability. 2020;12(18). doi: 10.3390/su12187802.##[4]Iyengar V, Chandrashekar SR.Factors that affect consumer decision making on choosing sustainable cosmetic products: an empirical study. Int J Progressive Res Engin Manag Sci. 2023;3(4):54-67.##[5]Andrean D, Anwar M. The Effect of Perceived Quality, Brand Image, and Price Perception on Purchase Decision. Proceedings of the 4th International Conference on Sustainable Innovation 2020-Accounting and Management (ICoSIAMS 2020). 2021.##[6]Pourjabbar Z, Niazmand Badabi M, Salami F, Sadeghi N, Amini M, Hajimahmoodi M.Quantification of Active Ingredients in Skin Lightening Creams Using HPLC Method in Iranian Market. Jundishapur J Natural Pharm Prod. 2025;20(3). doi: 10.5812/jjnpp-160628.##[7]Salman D, Tawfik Y, Samy M, Artal-Tur A.A new marketing mix model to rescue the hospitality industry: Evidence from Egypt after the Arab Spring. Future Business J. 2017;3(1):47-69. doi: 10.1016/j.fbj.2017.01.004.##[8]Booms B.Marketing strategies and organizational structures for service firms. In: Donnelly JH, George WR, editors. Marketing of services. Chicago, USA: American Marketing Association; 1981.##[9]Goi CL.A Review of Marketing Mix: 4Ps or More? Int J Market Stud. 2009;1(1). doi: 10.5539/ijms.v1n1p2.##

1 Affordability Analysis of Selected Medicines in Iran: A National Cross-sectional Survey Using World Health Organization Out-of-Pocket Methodology https://brieflands.com/journals/ijpr/articles/163774 10.5812/ijpr-163774 1 Background :Increased costs of prescription drugs impose tremendous economic burdens on patients globally, which usually result in low drug adherence and poor health outcomes. In Iran, out-of-pocket (OOP) expenditures are severe, particularly among vulnerable groups such as the elderly. This analysis reviews OOP expenditures of 51 medications in Iran to provide useful insights regarding healthcare policy. Objectives :To analyze OOP payments for medications in Iran during a seven-year period, revealing trends, financial needs, and policy requirements that increase financial protection and drug access. Methods :We included 51 medicines, meeting the WHO/HAI minimum sample size requirement for reliability (n = 50), consisting of the universal core list (n = 14) and a supplementary list based on local disease prevalence (n = 37). Following RECORD guidelines for observational studies, data were sourced from the two largest national health insurance funds [Social Security Organization (SSO), Iran Health Insurance Organization (IHIO)], covering the majority of the Iranian population, and pharmacy records from 2016 to 2022. OOP costs, insurance coverage, and affordability were analyzed using impoverishing health expenditure (IHE) and catastrophic health expenditure (CHE) metrics. To control for economic confounders, costs were adjusted using purchasing power parity (PPP). Joinpoint regression assessed annual OOP changes, with significance set at P-value < 0.05. Results :Over the seven-year period, PPP-OOP payments showed a non-significant decreasing trend [average annual percent change (AAPC): -1.2% for SSO; -1.38% for IHIO]. Despite this, OOP expenditure remained high, averaging approximately 40% of total medication costs. Significant heterogeneity was observed; for instance, Spironolactone saw the highest cost increase (AAPC +8.29%), while Insulin Glargine showed the largest decrease (AAPC -12.59%). High OOP payments were observed for medications like dexamethasone and chlorpromazine, while insulin and clozapine also carried high costs under insurance. The variability in OOP expenses across medicines highlights differences in pricing and insurance policies. Catastrophic expenses were prominent for certain medications, such as enoxaparin, especially at higher expenditure thresholds based on the 40% capacity-to-pay metric. Limitations included the use of administrative claims data subject to potential operational errors and the restriction of the sample to 51 medicines, which may limit generalizability to the broader pharmaceutical market. Conclusions :This research reveals high OOP spending for Iranian patients, with considerable drug-specific heterogeneity. The implications suggest that policy action in terms of price reform and wider insurance coverage is needed to minimize financial burden and ensure access to medicines. Further studies are required to determine the impact of high OOP spending on patient adherence and to inform specific health policies in Iran and beyond. 1 8 Fatemeh Soleymani Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Pharmaceutical Management and Economics Research Center (PMERC), Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran Iran Iran fsolemani@yahoo.com Amirhossein Abdi Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Iran ahossein.abdi78@gmail.com Alireza Mirzaei Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Iran alirezamirzaee1378@gmail.com Mohammad Mahdi Raeis Zadeh Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Pharmaceutical Management and Economics Research Center (PMERC), Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran Iran Iran mahdi.raeszadeh@yahoo.com Ali Zeinalkhani Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Iran ali.zeynalkhanii@gmail.com Behzad Fatemi Pharmaceutical Management and Economics Research Center (PMERC), Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran Iran behzad.fatemi63@gmail.com No Keyword 8.pdf [0]Vincent Rajkumar S.The high cost of prescription drugs: causes and solutions. Blood Cancer J. 2020;10(6):71. [PubMed ID: 32576816]. [PubMed Central ID: PMC7311400]. doi: 10.1038/s41408-020-0338-x.##[1]Luiza VL, Chaves LA, Silva RM, Emmerick IC, Chaves GC, Fonseca de Araujo SC, et al.Pharmaceutical policies: effects of cap and co-payment on rational use of medicines. Cochrane Database Syst Rev. 2015;2015(5). CD007017. [PubMed ID: 25966337]. [PubMed Central ID: PMC7386822]. doi: 10.1002/14651858.CD007017.pub2.##[2]Davari M, Haycox A, Walley T.The Iranian health insurance system; past experiences, present challenges and future strategies. Iran J Public Health. 2012;41(9):1-9. [PubMed ID: 23193499]. [PubMed Central ID: PMC3494208].##[3]Parnian E, Aboutorabi A, Mohseni M, Mousavi Isfahani H.Estimating Out-of-Pocket Payments Among Iranian Women with Breast Cancer. 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1 Dual TYK2/JAK1 Inhibition by Brepocitinib Reprograms Synoviocyte Pathobiology: Mechanistic Insights Into Targeted Therapy for Rheumatoid Arthritis https://brieflands.com/journals/ijpr/articles/166019 10.5812/ijpr-166019 1 Background :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. Objectives :To investigate the molecular and functional effects of brepocitinib on MH7A and RA-FLS synoviocytes, a key effector cell type in RA pathogenesis. Methods :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. Results :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. Conclusions :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. 1 11 Umar Saeed University College, Korea University, Seoul 02418, Republic of KOREA (South KOREA) Clinical and Biomedical Research Center (CBRC), Foundation University School of Health Sciences (FUSH), Foundation University Islamabad (FUI), Islamabad, Pakistan Republic of KOREA (South KOREA) Pakistan usaeed@chapman.edu Zahra Zahid Piracha Széchenyi István University, Győr, Hungary Institute of Graduate Studies and Research, Cyprus International University, Nicosia, Cyprus Hungary Cyprus zahra.zahid@riphah.edu.pk Andromeda M. Nauli Department of Biomedical Sciences, School of Medicine, Western Michigan University Homer Stryker, Kalamazoo, USA USA andromeda.nauli@wmed.edu Surya M. Nauli Department of Biomedical and Pharmaceutical Sciences, Chapman University, Irvine, United States United States nauli@chapman.edu No Keyword 9.pdf [0]Schuerwegh AJ, Ioan-Facsinay A, Dorjee AL, Roos J, Bajema IM, van der Voort EI, et al.Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis. Proc Natl Acad Sci USA. 2010;107(6):2586-91. [PubMed ID: 20133791]. [PubMed Central ID: PMC2823893]. doi: 10.1073/pnas.0913054107.##[1]Hunter TM, Boytsov NN, Zhang X, Schroeder K, Michaud K, Araujo AB.Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004-2014. Rheumatol Int. 2017;37(9):1551-7. [PubMed ID: 28455559]. doi: 10.1007/s00296-017-3726-1.##[2]Bartok B, Firestein GS.Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233-55. [PubMed ID: 20193003]. [PubMed Central ID: PMC2913689]. doi: 10.1111/j.0105-2896.2009.00859.x.##[3]Pap T, Dankbar B, Wehmeyer C, Korb-Pap A, Sherwood J.Synovial fibroblasts and articular tissue remodelling: Role and mechanisms. Semin Cell Dev Biol. 2020;101:140-5. [PubMed ID: 31956018]. doi: 10.1016/j.semcdb.2019.12.006.##[4]Bottini N, Firestein GS.Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat Rev Rheumatol. 2013;9(1):24-33. [PubMed ID: 23147896]. [PubMed Central ID: PMC3970924]. doi: 10.1038/nrrheum.2012.190.##[5]Wang Z, Wang J, Lan T, Zhang L, Yan Z, Zhang N, et al.Role and mechanism of fibroblast-activated protein-alpha expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis. Front Immunol. 2023;14:1135384. [PubMed ID: 37006278]. [PubMed Central ID: PMC10064071]. doi: 10.3389/fimmu.2023.1135384.##[6]Agashe RP, Lippman SM, Kurzrock R.JAK: Not Just Another Kinase. Mol Cancer Ther. 2022;21(12):1757-64. [PubMed ID: 36252553]. [PubMed Central ID: PMC10441554]. doi: 10.1158/1535-7163.MCT-22-0323.##[7]Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, et al.Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018;61(19):8597-612. [PubMed ID: 30113844]. doi: 10.1021/acs.jmedchem.8b00917.##[8]Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA.JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis. 2021;80(7):865-75. [PubMed ID: 33741556]. 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1 Vitamin P Significantly Inhibits the Expression of Ki67 and VEGF and Promotes the Apoptosis of Colorectal Cancer Cells https://brieflands.com/journals/ijpr/articles/163955 10.5812/ijpr-163955 1 Background :Colorectal cancer is a common malignant tumor of the digestive tract, with a high incidence and mortality rate. Ki67 and vascular endothelial growth factor (VEGF) play important roles in tumor cell proliferation and angiogenesis. Vitamin P is a natural flavonoid compound with various biological activities. Objectives :To explore the effects of vitamin P on the proliferation, angiogenesis, and apoptosis of colorectal cancer cells and its underlying molecular mechanisms. Methods :In vitro cultivation of human colorectal cancer cell lines (HCT116 and SW480) was performed. Vitamin P was added to the cells in varying quantities. Cell proliferation was identified using the CCK-8 technique. The flow cytometry method was used to determine the proportion of apoptotic cells. Real-time fluorescence quantitative PCR and Western blot methods were used to measure the expression levels of the VEGF and Ki67 genes and proteins. Secretion of VEGF was observed via immunofluorescence staining. Results :Vitamin P treatment significantly inhibited the proliferation of colorectal cancer cells in a dose-dependent manner. The half-maximal inhibitory concentrations (ICs50) at 48 hours were 72.3 μM (HCT116) and 85.6 μM (SW480). Moreover, in the vitamin P treatment group (42.7 - 68.9% and 35.4 - 61.2%), the secretion of VEGF decreased by 52.3 - 79.8%. The percentage of apoptotic cells induced by 20 - 80 μM vitamin P increased from 5.3% in the control group to 18.6 - 37.9%, with increased caspase-3 activity. In vivo experiments showed that vitamin P significantly inhibited the growth of colorectal cancer transplanted tumors and reduced the expression of Ki67 and VEGF in the tumors. Meanwhile, vitamin P treatment induced apoptosis of tumor cells, and this effect was closely related to the regulation of the Bax/Bcl-2 ratio and the promotion of caspase-3 activation. Vitamin P may play a regulatory role by inhibiting the phosphorylation of the STAT3 signaling pathway and downregulating the expression of proteins related to the PI3K/AKT pathway. Conclusions :Vitamin P can inhibit the malignant biological behavior of colorectal cancer cells by suppressing Ki67-mediated cell proliferation, blocking VEGF-related angiogenesis pathways, and activating mitochondrial apoptotic pathways. 1 8 Xin Zhao First Central Hospital of Tianjin Medical University, Tianjin, China Tianjin First Central Hospital, Tianjin, China China China ecolizx@hotmail.com Shang Guo Tianjin First Central Hospital, Tianjin, China China gsdxy2018@163.com Rongwei Shen Sun Yat-sen University First Affiliated Hospital, Guangzhou, China China rongweishen199608@126.com Wei Zhang Sun Yat-sen University First Affiliated Hospital, Guangzhou, China China wei_zhang1879@163.com Yamin Zhang First Central Hospital of Tianjin Medical University, Tianjin, China Tianjin First Central Hospital, Tianjin, China China China zhangyamin@nankai.edu.cn No Keyword 10.pdf [0]Wang F, Jin Y, Wang M, Luo HY, Fang WJ, Wang YN, et al.Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial. 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1 Phytochemicals Characterization and Antidiabetic Efficacy of <i>Muntingia calabura</i> L. Leaves Extract: In vitro and in vivo Studies https://brieflands.com/journals/ijpr/articles/169399 10.5812/ijpr-169399 1 Background :Muntingia calabura L. leaves are traditionally used in West Java to manage hyperglycemia, yet integrated evidence linking their chemical profile with bioactivity remains limited. Objectives :To profile secondary metabolites in M. calabura leaf extract (MCLE), evaluate antioxidat capacity, and perform an assessment of antihyperglycemic efficacy in a diabetic rat model. Methods :Muntingia calabura L. leaves extract was characterized by ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC–HRMS/MS). Antioxidant activity was measured using the ABTS•⁺ decolorization assay. Antihyperglycemic activity was evaluated in streptozotocin (STZ)-induced diabetic rats treated orally with MCLE (125 or 250 mg/kgBW) for 14 days. Fasting blood glucose (FBG), 2-hour postprandial glucose (2hPP), and body weight were analyzed using two-way repeated-measures analysis of variance (ANOVA). Results :Ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry annotated diverse secondary metabolites, with the most intense signals assigned to 5-hydroxy-6,7-dimethoxy-2-phenyl-4H-chromen-4-one (19.99%), isokaempferide (16.94%), and scrophulein (10.90%). Muntingia calabura L. leaves extract and its n-hexane and ethyl acetate fractions exhibited ABTS•⁺ radical scavenging activity. In STZ-induced rats, significant group × day interactions were observed for all outcomes (P < 0.001). The 250 mg/kgBW dose attenuated diabetes-associated weight loss and reduced FBG (P < 0.01), and 2hPP at this dose (134.0 ± 4.0 mg/dL) was not significantly different from the normal control or glibenclamide groups (P > 0.05). Conclusions :Muntingia calabura L. leaves extract demonstrated antihyperglycemic activity in STZ-induced diabetic rats, improving both FBG and 2hPP alongside measurable antioxidant capacity. 1 10 Raden Maya Febriyanti Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia Herbal Study Center, Universitas Padjadjaran, Indonesia Indonesia Indonesia raden.maya@unpad.ac.id Mayra Fauzia Bachelor Program in Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia Indonesia mayra22002@mail.unpad.ac.id Nurqisthi Iqlimia Bachelor Program in Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia Indonesia nurqisthi22001@mail.unpad.ac.id Aalbrecht Alby Irawan Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Indonesia Indonesia aalbrecht23001@mail.unpad.ac.id Dwintha Lestari Faculty of Pharmacy, Universitas Muhammadiyah Bandung, Indonesia Indonesia dwinthalestari@umbandung.ac.id Yoppi Iskandar Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia Herbal Study Center, Universitas Padjadjaran, Indonesia Indonesia Indonesia y.iskandar@unpad.ac.id Yasmiwar Susilawati Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia Herbal Study Center, Universitas Padjadjaran, Indonesia Indonesia Indonesia yasmiwar@unpad.ac.id Ajeng Diantini Department of Pharmacological and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia Indonesia ajeng.diantini@unpad.ac.id No Keyword 11.pdf [0]Dasumani M, Houénafa SE, Cédric GL, Lassong BS, Moore SE.Deterministic and stochastic models for analyzing the dynamics of diabetes mellitus. 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1 Establishing 18F-PSMA-1007 Production in Armenia: Radiosynthesis and Comprehensive Quality Control https://brieflands.com/journals/ijpr/articles/169428 10.5812/ijpr-169428 1 Background :18F-prostate-specific membrane antigen (18F-PSMA-1007) is a recognized positron emission tomography (PET) radiotracer commonly used for prostate tumor imaging due to its excellent tumor-to-background contrast and advantageous pharmacokinetics. Although 18F-PSMA-1007 has been extensively manufactured and used in many countries, it has not been available in Armenia until now. The aim of this work is to synthesize 18F-PSMA-1007 for the first time in Armenia for local clinical implementation and to demonstrate the reproducibility of the process. Objectives :Based on this, the objective of this work was to synthesize 18F-PSMA-1007 with high synthesis efficiency and chemical purity, which would enable us to perform precise studies in the field of prostate cancer diagnosis. The start of its production also represents a major advancement in the country's nuclear medicine capabilities. Methods :This study presents the initial report of the first successful production of 18F-PSMA-1007 in Armenia, detailing the synthesis method, quality control criteria, and adherence to good manufacturing practices (GMP) standards to ensure safe and efficient clinical use. An 18 MeV cyclotron was used to produce the 18F radioisotope needed for the production of the radiopharmaceutical. Starting ingredients, chromatographic resins, and a semi-automatic device were used in closed lead-shielded cells to synthesize 18F-PSMA-1007. The chemical reaction started after 18F ions were eluted into the reaction vessel using tetrabutylammonium bicarbonate (TBA). Residual solvents were then removed at 110°C for 5 minutes. The fluorination process was carried out using one-step radiolabeling at 95°C for 10 minutes, after which the resulting product was purified on a chromatographic resin for 10 minutes. Finally, 18F-PSMA-1007 was eluted into the dispensing cell. Comprehensive quality control analyses have been carried out in accordance with the guidelines of the European Pharmacopoeia (EP). To demonstrate the reproducibility of the synthesis of 18F-PSMA-1007 at the Radioisotope Production Center, as well as the quality control results, the work also presents the results of two additional syntheses and the corresponding quality control. Results :The successful synthesis of 18F-PSMA-1007 in Armenia, with a 52.2 % decay not corrected yield and 95 % purity, marks a significant advancement in the country’s nuclear medicine capabilities, providing highly sensitive and accurate PET examinations. The product met all specifications. Conclusions :The start of 18F-PSMA-1007 production locally has become a significant turning point for Armenian nuclear medicine. In addition to providing patients in the nation with access to cutting-edge PET diagnostic techniques, it also opens the door for the domestic radiopharmaceutical industry to grow and concentrate on exports. 1 13 Hayk Petrosyan Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia Yerevan State University, 1 A. Manoogian str․, 0025 Yerevan, Armenia Armenia Armenia haykpetrosyan2@gmail.com Marine Mnatsakanyan Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia Armenia marina_mnatsakanyan@yahoo.com Isabella Karapetyan Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia Armenia isabellakarati@gmail.com Andranik Manukyan Alikhanyan National Science Laboratory, 2 Alikhanyan Brothers str., 0036, Yerevan, Armenia Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia Armenia Armenia andoman89@gmail.com Gurgen Elbakyan Alikhanyan National Science Laboratory, 2 Alikhanyan Brothers str., 0036, Yerevan, Armenia Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia Armenia Armenia gurgenelbakyan@gmail.com Davit Arshakyan Alikhanyan National Science Laboratory, 2 Alikhanyan Brothers str., 0036, Yerevan, Armenia Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia Armenia Armenia davitarshakyan.1996@gmail.com Nona Ginosyan Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia Armenia nona_ginosyan@yahoo.com Armine Badeyan Radioisotope Production Center, 38/7 Halabyan str., 0036 Yerevan, Armenia National Center of Oncology Named After V.A. Fanarjian, 76 Fanarjyan Str., 0052, Yerevan, Armenia Armenia Armenia badeyan.a93@gmail.com No Keyword 12.pdf [0]Eiber M, Fendler WP, Rowe SP, Calais J, Hofman MS, Maurer T, et al.Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy. J Nucl Med. 2017;58(Suppl 2):67S-76S. [PubMed ID: 28864615]. doi: 10.2967/jnumed.116.186767.##[1]Rowe SP, Drzezga A, Neumaier B, Dietlein M, Gorin MA, Zalutsky MR, et al.Prostate-Specific Membrane Antigen-Targeted Radiohalogenated PET and Therapeutic Agents for Prostate Cancer. J Nucl Med. 2016;57(Suppl 3):90S-6S. [PubMed ID: 27694179]. [PubMed Central ID: PMC5093916]. doi: 10.2967/jnumed.115.170175.##[2]Mingels C, Bohn KP, Rominger A, Afshar-Oromieh A, Alberts I.Diagnostic accuracy of [(18)F]PSMA-1007 PET/CT in biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging. 2022;49(7):2436-44. [PubMed ID: 35067735]. 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[PubMed Central ID: PMC9777208]. doi: 10.3390/diagnostics12123176.##[14]Sprute K, Kramer V, Koerber SA, Meneses M, Fernandez R, Soza-Ried C, et al.Diagnostic Accuracy of (18)F-PSMA-1007 PET/CT Imaging for Lymph Node Staging of Prostate Carcinoma in Primary and Biochemical Recurrence. J Nucl Med. 2021;62(2):208-13. [PubMed ID: 32817141]. [PubMed Central ID: PMC8679593]. doi: 10.2967/jnumed.120.246363.##[15]Ioppolo JA, Nezich RA, Richardson KL, Morandeau L, Leedman PJ, Price RI.Direct in vivo comparison of [(18)F]PSMA-1007 with [(68)Ga]Ga-PSMA-11 and [(18)F]AlF-PSMA-11 in mice bearing PSMA-expressing xenografts. Appl Radiat Isot. 2020;161:109164. [PubMed ID: 32321698]. doi: 10.1016/j.apradiso.2020.109164.##[16]Rahbar K, Weckesser M, Ahmadzadehfar H, Schafers M, Stegger L, Bogemann M.Advantage of (18)F-PSMA-1007 over (68)Ga-PSMA-11 PET imaging for differentiation of local recurrence vs. urinary tracer excretion. Eur J Nucl Med Mol Imaging. 2018;45(6):1076-7. [PubMed ID: 29445927]. doi: 10.1007/s00259-018-3952-0.##[17]Kuten J, Fahoum I, Savin Z, Shamni O, Gitstein G, Hershkovitz D, et al.Head-to-Head Comparison of (68)Ga-PSMA-11 with (18)F-PSMA-1007 PET/CT in Staging Prostate Cancer Using Histopathology and Immunohistochemical Analysis as a Reference Standard. J Nucl Med. 2020;61(4):527-32. [PubMed ID: 31562225]. doi: 10.2967/jnumed.119.234187.##[18]Kesch C, Kratochwil C, Mier W, Kopka K, Giesel FL.(68)Ga or (18)F for Prostate Cancer Imaging? J Nucl Med. 2017;58(5):687-8. [PubMed ID: 28408526]. doi: 10.2967/jnumed.117.190157.##[19]Tayara O, Poletajew S, Malewski W, Kunikowska J, Pelka K, Kryst P, et al.Prostate-Specific Membrane Antigen Expression in Patients with Primary Prostate Cancer: Diagnostic and Prognostic Value in Positron Emission Tomography-Prostate-Specific Membrane Antigen. Curr Oncol. 2024;31(8):4165-77. [PubMed ID: 39195294]. 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1 Hydroalcoholic Extract of <i>Ferula aucheri</i> Shows Anti-depressant Effect Against Lipopolysaccharide-Induced Depression in Mice: Involvement of NF-κB and TLR4 Signaling Pathway https://brieflands.com/journals/ijpr/articles/166242 10.5812/ijpr-166242 1 Background :Depression is one of the most common neuropsychiatric disorders worldwide. Lipopolysaccharide (LPS), a bacterial endotoxin, induces depressive-like behaviors by activating microglia and promoting the release of pro-inflammatory mediators, including nitric oxide, eicosanoids, and various cytokines. Owing to its rich content of flavonoids, phenolic compounds, and terpenoids, Ferula aucheri possesses potent antioxidant and anti-inflammatory properties, which may contribute to its potential as an alternative treatment for depression.Objectives :This study aimed to evaluate the antidepressant-like effects of the hydroalcoholic extract of F. aucheri on LPS-induced depression in mice. Methods :After preparation of the hydroalcoholic extract of F. aucheri, 30 mice were randomly divided into five groups: (1) Control; (2) LPS (1 mg/kg, i.p.); (3) LPS+fluoxetine (20 mg/kg, i.p.); (4) LPS+F. aucheri extract (100 mg/kg, i.p.); and (5) LPS+F. aucheri extract (200 mg/kg, i.p.). Lipopolysaccharide was administered to induce depressive-like behaviors, and after 24 hours, behavioral assessments were conducted using the forced swim test (FST), tail suspension test (TST), and open field test (OFT). Subsequently, immunohistochemical analysis was performed to assess the expression of toll-like receptor 4 (TLR4) and NF-κB in the brain tissue. Results :The FST and TST results revealed that treatment with F. aucheri extract significantly reduced immobility time compared to the LPS group, particularly at the 200 mg/kg dose, which showed superior efficacy even compared to fluoxetine. The OFT confirmed that the observed behavioral changes were not due to alterations in locomotor activity. Immunohistochemical analysis revealed that LPS significantly increased the expression of TLR4 and NF-κB in the brain. Notably, treatment with F. aucheri (200 mg/kg) significantly attenuated the expression of both biomarkers compared to the LPS group (#P < 0.05 and ##P < 0.01, respectively). Conclusions :The findings suggest that F. aucheri exhibits antidepressant-like effects in an LPS-induced model of depression, potentially mediated through modulation of neuroinflammatory pathways involving TLR4 and NF-κB. Given its promising preclinical efficacy and mechanistic relevance, F. aucheri could be considered an appropriate candidate for future clinical investigations as an antidepressant agent. 1 12 Mohammad Mehdi Gravandi Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran mehdigravandi@yahoo.com Maryam Naseri Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran naseri.mn91@gmail.com Nasim Jamshidi Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran dr.jamshidi2018@gmail.com Samira Shirooie Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran shirooie@gmail.com No Keyword 13.pdf [0]Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al.Major depressive disorder. Nat Rev Dis Primers. 2016;2:16065. 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